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Professor Charles Tyler

Professor of Environmental Biology/ Academic Lead

4450

Geoffrey Pope 314b

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

Professor Charles Tyler observing fish in the aquarium

Overview

I am a reproductive physiologist and environmental biologist. My research spans investigations into the mechanisms of endocrine disrupting chemicals and nanoparticle ecotoxicology to assessing population level effects of environmental contaminants in wildlife, principally fish. Much of my research includes applying genetic and genomic techniques to understand the basis of physiological processes and the mechanisms through which they are disrupted by environmental contaminants. I have a deep passion for wildlife and my research projects also include studies on the natural ecology of insects, fish, and birds.

I was Director of Research ( 2003-2009) and I now lead the Environmental Biology research theme and act as Deputy Head for Biosciences. I am also an Academic Lead for the College of Life and Environmental Sciences. I play roles also in leading various strategic research partnerships with external partners including AstraZeneca and cefas.

Qualifications

2003 DSc University of Lancaster
1984-1987 PhD University of Aston
1983-1984 MSc in Applied Fish Biology, University of Plymouth
1980-1983 BSc (Hons) Biological Sciences, University of Lancaster

Career

2010-2015 Chief Science Advisor for United Kingdom-Japan Research into Endocrine Disruption, Department of Food and Rural Affairs
2010-present Deputy Head Biosciences, Academic Lead College of Life and Environmental Sciences
2005-2010 Director of Research for Biosciences, University of Exeter
2005-2010 UK Supervisor for United Kingdom-Japan Research into Endocrine Disruption, Department of Food and Rural Affairs
2005-2008 Honorary Research Fellow of the Institute of Zoology, London
2000-present Professor in Environmental and Molecular Fish Biology, University of Exeter
1999-2000 Reader in Biological Sciences, Brunel University
1996-1999 Senior Lecturer in Biological Sciences, Brunel University
1990-1996 Lecturer in Biological Sciences, Brunel University

Honours/Awards

2012 Elected Fellow for the Society of Biology
2012 The Fisheries Society of the British Isles Beverton Medal for ground breaking research in fish biology
2011 University of Exeter Impact Award for Outstanding contribution to Policy and Public Services
2008-to date Honorary Chair, Peninsular College for Medicine and Dentistry
2005-to date Honorary Research Fellow of the Institute of Zoology, London

Research group links

Environmental Biology

Professor Charles Tyler in the aquarium

Research

Research interests

Endocrine Disruption: A major focus of my research interest is endocrine disruption, the study of chemicals that alter hormone function which can lead to adverse impacts on health. Our work with colleagues at Brunel University was some of the very first research to show that effluents from wastewater treatment works causes feminisation of male fish. My teams work has subsequently proven that feminisation of wild roach living in UK rivers is caused by exposure to treated sewage effluents. Using a targeted biological screening of chemically fractionated bile from effluent exposed fish, with collaborators (University of Sussex), we have been able to identify the suite of feminising chemicals in effluent discharges, principally environmental oestrogens, and through laboratory exposures proven they contribute to the feminisation of wild fish in UK rivers. These chemicals include natural and synthetic steroid oestrogens, and alkylphenolic compounds. This original work has been very highly cited. Combining empirical studies with models including Concentration Addition/Joint Independent Action, my team has further established that oestrogenic chemicals can be additive in their effects and these findings have had a widespread and international influence. More recently we discovered the widespread presence of anti-androgenic chemicals in wastewater effluent discharges and my team is now studying their possible contribution to the feminisation of fish living in UK rivers.

A major question we are now trying to establish is whether wild fish (roach, Rutilus rutilus) populations are impacted adversely by exposure to oestrogenic effluent discharges. Undertaking controlled breeding studies in the laboratory and applying DNA microsatellites to assess parentage with have proven that moderately to severely feminised males have a reduced capacity to compete with normal males to sire offspring. We have further shown that life long exposure to an oestrogenic effluent (at full strength) causes complete gonadal feminisation of males, some of which were able to breed as females. In some of our most current work we are applying DNA microsatellites to establish whether roach populations living in rivers heavily polluted with wastewater effluents have a reduced effective population breeding size. If so, this will show that exposure to wastewater effluents at these sites is fundamentally affecting population genetics.

The mechanisms of action and pathways of effects have been established for very few endocrine active chemicals and this has been another key focus of my teams work. Targeted single gene approaches, gene arrays and more recently sequencing technologies have been applied to unravel some of the molecular mechanisms of oestrogenic disruption (including for mixture effects) and other forms of chemical toxicity. Other ongoing projects include studying the metabolome and xenometabolome in fish in response to exposure to effluents and individual EDCs with Profs Hill (University of Susses) and Prof Viant (University of Birmingham). Most recently, working with Dr Kudoh, also at Exeter, we have developed a ERE-GFP transgenic zebrafish that is exquisitely sensitive to oestrogens that allows us to identify – through the expression of a green fluorescent protein - where different oestrogens interact in the body and in real time. This is a very power tool that we are now using to investigate the potential for wider health impacts of exposure to environmental, oestrogens. We are currently attempting to develop a similar model for (anti-) androgens. Members of my team also work on other chemical contaminants of environmental and human health concern including pesticides and pharmaceuticals.

I have an interest also in the development and application of in vitro systems for understanding mechanisms of action and reducing animal use. These systems include cell culture (especially hepatocytes), recombinant cell lines and receptor transactivation assays.

Almost all of our work on endocrine disruption is focused on fish, but we have also worked on birds (Dipper, Cinclus cinclus), mammals (Otter, Lutra lutra) and various invertebrates.

Nanotoxicology: Nanotechnology is an emerging field of science that deals with engineered molecules of an extremely small size (1-100 nanometres). Because of size – related changes in physico – chemical properties, substances at the nanoscale display optical, magnetic and chemical properties that can differ greatly from the standard material enabling diverse commercial applications. Nanoparticles are currently used in products such as suntan lotion, cosmetics, clothing, cleaning materials, medicines and food and assessing the potential health risks associated with exposure to nanoparticles is now recognised as being a major international research priority. Working with other members of the Envrionment and Evolution theme (Prof Galloway) my team is researching into the effects of metal and metal oxide nanoparticles, principally in fish, but also some invertebrates.

Most of our research on nanomaterials has been focused on understanding their bioavailability, including for exposures in natural waters and in effluents. This work is being complemented by in vitro studies with various fish cell types including hepatocytes, gut and gill cells to investigate how nanoparticles cross cell membranes and their fate within cells. Further methods applied in this work include whole mount in situ hybridisation to investigate specific gene responses in the bodies of whole embryos. Various analytical techniques and state of the art imaging techniques are being employed to monitor particle fate and behaviour in the water and fish, including RAMAN scattering. In our work to date we have found that many metal nanomaterials ( ceria, zinc, titania) show little toxicity to fish. In contrast silver nanoparticles are toxic, albeit that this toxicity may result from dissolution and free silver, rather than an innate function of the particles themselves. In our current work we are applying whole genome sequencing on exposed zebrafish embryos and the target tissues for specific nanomaterials in larger fish to further establish the effect mechanisms of metal/metal oxide nanoparticles in the body and thus help unravel some of the possible health concerns linked with these materials. This work is funded by very diverse sources including Research Councils, DEFRA, and various industries reflecting the multi-stakeholder interest.

Disease: I have a growing interest in the effects of combined environmental stressors on wildlife, including features of climate change. A project that has recently been initiated with the Centre for Environment, Fisheries and Aquaculture Science is the application of sequencing technologies to understand the pathogenic process of white spot virus, a major disease organism for cultures and wild crustaceans.

Basic Biology: Underpinning all of my teams ecotoxicology work is my interest in the basic biology of fish and other wildlife species. Here primary interests include understanding the mechanisms controlling sexual development and reproduction. To be able to assess what is abnormal for exposure to an environmental stressor, it is important to understand the normal basic processes and variation.

Major research activities and findings from my team include the following:

Sexual differentiation: My team has established the timing and mapped histologically the process of sexual differentiation in the roach, Rutilus rutilus, a sentinel species for studies on chemical effects in wild fish in UK freshwaters, and in the fathead minnow and zebrafish, both key laboratory species. They have further identified some of the molecular mechanisms controlling sexual differentiation in these fish.

Oogenesis (egg development) and Spermatogenesis: We have mapped histologically the process of oogenesis and spermatogenesis in roach, fathead minnow and zebrafish. In this work we have especially focused on the process of vitellogenesis (provision and uptake of yolk into oocytes) and established some of the endocrine and molecular mechanisms controlling yolk uptake and processing. Our work has included the cloning and sequencing of the first cDNA for a fish vitellogenin receptor, establishing the developmental expression and cellular localisation of the vitellogenin receptor mRNA in fish oocytes, and the cloning and sequencing of some of the first yolk processing enzymes (cathepsins) in oocytes. My team has also developed some of the first assays to quantify vitellogenins in fish, which have been vital for work on endocrine disruption.

Endocrine control of fecundity: Very little is known about the determinants of fecundity in any animal. Fish, because they are highly fecund, provide excellent model systems for investigating the endocrine control of oocyte recruitment and growth - the associated titres of plasma hormones are considerably higher than for most other animals. Applying the technique of unilateral ovariectomy (to manipulate oocyte recruitment) we have identified some of the hormones controlling ovarian development.

Puberty: We have cloned the KiSS I receptor in various fish species, identified and cloned some of the KiSS peptin ligands (the first to do so in fish) and mapped them to their chromosomes. We have established the ontogeny and localization of expression of KiSS 1 receptor in the brain in both male and female fathead minnow during sexual development and shown how this expression aligns with the expression of an extensive suite if other genes involved in mediating sexual development (e.g. the GnRHs). The ability to control puberty in fish would be of great significance in the aquaculture of many fish species.

Sexual behaviour: The zebrafish is one of the major models for studies in ecotoxicology, yet very little is known about its basic biology. My lab team has contributed to filling this knowledge gap through extensive studies on its reproductive biology. In this work we have projects studying the behaviour of the zebrafish in breeding colonies. This work is principally focused on understanding the interactions and hierarchies that develop in zebrafish colonies to advance our understanding on their breeding dynamics in natural populations. In this work, detailed studies on male-male, male-female and female-female interactions are being established for different sized colonies and the reproductive success of individuals in those colonies are determined through genotyping of the offspring produced (through the use of DNA microsatellites). Our work on zebrafish is principally laboratory based, but we also have some ongoing studies on natural colonies in Bangladesh. This work also includes the development and application of population models.

New Models: I am always interested in exploring new models for understanding basic reproductive processes and/or exploiting them for better understanding possible health effects of environmental contaminants. A model we are currently working on is a Xenotoca spp, that gives birth to live young. Currently we are studying the basic reproductive biology, but our longer term plan is to use this model to investigate maternal transfer of EDCs, pharmaceuticals and nanomaterials and their health effects on developing embryos.

Wildlife Biology. My passion in life is wildlife and I have a series of projects with various external partners including the UK Environment Agency, defra, cefas, RSPB, BTO, Dartmoor National Park studying the ecology of various insects and birds(most notably the Cuckoo).

Current Funding

2010 -2013 Joint US-UK (NERC) Research Program: Environmental Behaviour, Bioavailability and Effects of Manufactured Nanomaterials (EPA-G2008-STAR-R1) - (£203 000 PI to Exeter, PI., total grant £3M). Consortium for Manufactured Nanomaterial Bioavailability & Environmental Exposure (nanoBEE).
2010 -2013 EU - Qnano. Infrastructure and toxicology assessment unit. (Euros 285 991, Co-I)
2010 Wolfson. Zebrafish Developmental Biology Imaging Unit (infrastructure and microscopes) (£400k PI).
2011-2013 DEFRA (£160 000 - PI). Emerging endocrine disrupting chemicals. UK/Japan partnership Grant. Pending
2011-2014 NERC(£420 000 - Development and Application of Transgenic Biosensor Zebrafish
for Assessing the Environmental Health Impacts of Anti-Androgens.
2011 CEFAS (£17 000 –co PI). Investigating the potential molecular mechanisms associated with white spot virus resistance in Carcinus maenas
2011-2014 CEFAS (£37 500 - co I). The Implications of Ocean Acidification in Combination with Chemical Stressors for Juvenile Fish (50% PhD studentship support)
2011-2014 Leverhulme (£143 800 - co I). The Evolution of Cooperation in Structured Animal Societies
2011-2014 Interegg European Neurosciences Project (Euros140 00 –PI).
2012 DEFRA/ Open Innovation Fund. (£60 000 - co I) CB0456 - Global NanoMaPPP - Ecotoxicology of
Metal Oxide Nanomaterials in the Aquatic Environment
2012-2015 Cefas- (£300k, drawing down further support from the UoE Open Innovation platform - value of total grant £532 000, PI). Building a Molecular Platform for Understanding the Host-Pathogen Interface in Invertebrates.
2012-15 EU (£300k, co-I). ( CLEANSEAS) . Microplastics in the Marine Environment
2012 British Ecological Survey (£1,860 - PI): Niche partitioning and factors determining success of ground nesting birds, including Cuckoo parasitism, on Dartmoor
2012-15 EU. (540k Euros, PI). NanoMILE (10 million Euro Consortium grant). Nanoparticles in the Environment.
2013 Cefas. (£28,854 PI). Exposure effects of natural plants extracts on fish
2013-15 BASF (£144 000, co-I with Prof Galloway). Ecotoxicology of nanopolymer dispersions. A case study of aqueous acrylic ester copolymers.
2013-14 Spanish Government (£30 000 co-I)Molecular identification of sex, reproductive stage and fecundity in fish of commercial interest: mechanisms, aplications and exploitation. SEXOVUM.
2013-14 NERC (FENAC/2012/11/002; £24 000 co-I). Transfer of Bulk and Nanoparticulate Cerium between a Mussel and a Crab
2013-14 NERC (FENAC/2012/11/001; £24 000 P.I). Biological uptake and effects of metal oxide nanomaterials in early life stages of fish and for exposure to a complex mixture
2013-16 NERC (£578 000 P.I., £399 000 to Exeter). Can roach, Rutilus rutilus, adapt to the harmful effects of oestrogen exposure from waste water treatment work effluents?
2013-16 German Gov. (40 000 Euros P.I). Consultant for the German National programme on Nanomaterials
2013-15 BBSRC (£149,724, PI) Exploiting Transgenic Zebrafish Embryos/Larvae for Systems- Wide Analysis of Endocrine Disrupting Chemicals
2013-14 Defra ((£64 000)Predicting Reproductive Failure in Frogs using Non-destructive Biomarkers – A Pilot Study
2013-15 NERC/TSB/KTP –Develop and Validate Numerical Modelling Capability for HR Wallingford - (£247 870 co-I)
2013-16 EU (€139,600 Co-I, total consortium €6million) GuideNano: Assessment and mitigation of nano-enabled product risks on human and environmental health

Research networks

Universities/Academic Institutes

National: Cardiff University (Dr. Kille), Brunel University (Prof. Sumpter/Dr. Jobling), University of Liverpool (Prof.Cossins), University of Lancaster (Prof Wit, Dr Thomas), University of Birmingham (Prof. Chipman, Dr. Viant, Dr Lead), University of East Anglia (Dr. Gage), University of Plymouth (Dr. Handy), University of Sussex (Dr Hill), Imperial University (Dr Ebbles, Prof Nicholson), University College, London (Dr Lorenzi), Kings College, London (Prof Hogstrand, Dr Bury).
International: University of Ancona, Italy (Dr. Carnevali), University of Frankfurt, Germany (Prof. J and Dr. U Oehlmann), University of Anantapur, India (Dr. Gundala), University of Heidelberg, Germany (Prof. Braunbeck), Centre for Integrative Biosciences, Okazaki, Japan (Prof. Iguchi, Dr. Katsu), University of Victoria, Canada (Dr. Helbing), University of Florida, USA (Prof Lou Guillette, Prof. Denslow), University of Pretoria, South Africa (Prof. Boreman), University of Bergen, Norway (Prof Ian Mayer), University of Utrecht, The Netherlands (Prof R. Schulz).
Actively involved with the ERASMUS and SOCRATES programme for the exchange of research students to undertake projects in research laboratories throughout Europe. Through this programme I have supervised 11 students from The Netherlands, Italy and Portugal.

Government Agencies and Industry

Government Agencies: Environment Agency, UK (Dr. A. Henshaw, Dr. Benstead, Nick Cartwright), The Centre for Environment, Fisheries and Aquaculture Sciences, UK (Dr. Katsiakdaki, Dr Stentiford), CEH, Wallingford (Dr Johnston), Plymouth Marine Laboratory, Plymouth, UK (Prof. Readman), DEFRA (Dr Mike Roberts) Cedex, France (Dr. Procher and Dr. Flammaron), National Institute of Fisheries, Seattle USA (Prof. Swanson), US Environment Protection Agency, Duluth, USA (Prof. Ankley), Gulf Breeze (Prof Benson).
Industry: Astra-Zeneca, Brixham Environmental Laboratory, Brixham, UK (Dr. Brown, Dr. Owen, Dr. Winter, Dr Hetheridge, Dr. Ball), Essex and Suffolk Water plc, UK (A. Jambakhsh & D.Walker), Biosense Laboratories AS, Bergen, Norway. (Prof. Goksoyr), Schering AG Experimental Toxicology, Germany (Dr. Laenge), Syngenta (Dr Thornbeck), Anglian Water plc UK (Dr.Rostron), UK Water Institute for Research, Water Research Council-NSF, UK (Dr. Johnson).
These are collaborations that have provided funding for my research and/or from which joint research papers have resulted. I presently have 7 Research Council-CASE studentships. I am also involved with the EUREKA programme that promotes an exchange of scientific research between academic institutes and industry.

Research Council Knowledge Transfer Schemes

I have been a partner in 6 (NERC/TSB –funded) knowledge transfer schemes

Publications

Key publications | Publications by category | Publications by year

Key publications

Verbruggen B, Gunnarsson L, Kristiansson E, Österlund T, Owen SF, Snape JR, Tyler CR (In Press). ECOdrug: a database connecting drugs and conservation of their targets across species. Nucleic Acids Res, 46(D1), D930-D936. Abstract. Author URL.

Le Page G, Gunnarsson L, Snape J, Tyler CR (In Press). Integrating human and environmental health in antibiotic risk assessment: a critical analysis of protection goals, species sensitivity and antimicrobial resistance. Environ Int, 109, 155-169. Abstract. Author URL.

Brown AR, Green J, Moreman J, Gunnarsson L, Mourabit S, Ball J, Winter M, Trznadel M, Correia A, Hacker C, et al (2018). Cardiovascular Effects and Molecular Mechanisms of Bisphenol a and its Metabolite MBP in Zebrafish. Environmental Science and Technology Full text.

Brown AR, Owen SF, Peters J, Zhang Y, Soffker M, Paull GC, Hosken DJ, Wahab MA, Tyler CR (2015). Climate change and pollution speed declines in zebrafish populations. Proc Natl Acad Sci U S A, 112(11), E1237-E1246. Abstract. Author URL. Full text.

Hamilton PB, Lange A, Nicol E, Bickley LK, De-Bastos ESR, Jobling S, Tyler CR (2015). Effects of Exposure to WwTW Effluents over Two Generations on Sexual Development and Breeding in Roach Rutilus rutilus. Environ Sci Technol, 49(21), 12994-13002. Abstract. Author URL.

Brown AR, Gunnarsson L, Kristiansson E, Tyler CR (2014). Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1656). Abstract. Full text.

Publications by category

Books

Tyler CR, Parsons A, Rogers NJ, Lange A, Brown AR (2019). Plasticisers and Their Impact on Wildlife. Abstract.

Journal articles

Winter MJ, Windell D, Metz J, Matthews P, Pinion J, Brown JT, Hetheridge MJ, Ball JS, Owen SF, Redfern WS, et al (In Press). 4-dimensional functional profiling in the convulsant-treated larval zebrafish brain. Sci Rep, 7(1). Abstract. Author URL. Full text.

Hamilton PB, Rolshausen G, Uren Webster TM, Tyler CR (In Press). Adaptive capabilities and fitness consequences associated with pollution exposure in fish. Philos Trans R Soc Lond B Biol Sci, 372(1712). Abstract. Author URL.

Johnston HJ, Verdon R, Gillies S, Brown DM, Fernandes TF, Henry TB, Rossi AG, Tran L, Tucker C, Tyler CR, et al (In Press). Adoption of in vitro systems and zebrafish embryos as alternative models for reducing rodent use in assessments of immunological and oxidative stress responses to nanomaterials. Crit Rev Toxicol, 48(3), 252-271. Abstract. Author URL.

Le Page G, Gunnarsson L, Snape J, Tyler CR (In Press). Antibiotic risk assessment needs to protect both environmental and human health. Environ Int, 115, 397-399. Author URL.

Bickley LK, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (In Press). Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas). Environ Sci Technol, 51(3), 1764-1774. Abstract. Author URL. Full text.

Mintram KS, Brown AR, Maynard SK, Thorbek P, Tyler CR (In Press). Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish. Crit Rev Toxicol, 48(2), 109-120. Abstract. Author URL. Full text.

David A, Lange A, Abdul-Sada A, Tyler CR, Hill EM (In Press). Disruption of the Prostaglandin Metabolome and Characterization of the Pharmaceutical Exposome in Fish Exposed to Wastewater Treatment Works Effluent As Revealed by Nanoflow-Nanospray Mass Spectrometry-Based Metabolomics. Environ Sci Technol, 51(1), 616-624. Abstract. Author URL.

Green JM, Lange A, Scott A, Trznadel M, Wai HA, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR, et al (In Press). Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish. Sci Rep, 8(1). Abstract. Author URL. Full text.

Windsor FM, Ormerod SJ, Tyler CR (In Press). Endocrine disruption in aquatic systems: up-scaling research to address ecological consequences. Biol Rev Camb Philos Soc, 93(1), 626-641. Abstract. Author URL.

Brask JB, Croft D, Edenbrow M, James R, Bleakley BH, Ramnarine IW, Heathcote R, Tyler C, Hamilton P, Dabelsteen T, et al (In Press). Evolution of non-kin cooperation: social assortment by cooperative phenotype in guppies. Royal Society Open Science Full text.

Holder PJ, Jones A, Tyler CR, Cresswell JE (In Press). Fipronil pesticide as a suspect in historical mass mortalities of honey bees. Proc Natl Acad Sci U S A, 115(51), 13033-13038. Abstract. Author URL. Full text.

Ogino Y, Tohyama S, Kohno S, Toyota K, Yamada G, Yatsu R, Kobayashi T, Tatarazako N, Sato T, Matsubara H, et al (In Press). Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR. J Steroid Biochem Mol Biol, 184, 38-46. Abstract. Author URL.

Green JM, Metz J, Lee O, Trznadel M, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR (In Press). High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish. Environ Sci Technol, 50(12), 6536-6545. Abstract. Author URL.

Parsons A, Lange A, Hutchinson TH, Miyagawa S, Iguchi T, Kudoh T, Tyler CR (In Press). Molecular mechanisms and tissue targets of brominated flame retardants, BDE-47 and TBBPA, in embryo-larval life stages of zebrafish (Danio rerio). Aquatic Toxicology

Brominated flame retardants are known to disrupt thyroid hormone (TH) homeostasis in several vertebrate species, but the molecular mechanisms underlying this process and their effects on TH-sensitive tissues during the stages of early development are not well characterised. In this study, we exposed zebrafish (Danio rerio) embryo-larvae to 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and tetrabromobisphenol a (TBBPA) via the water for 96 h from fertilisation and assessed for lethality, effects on development and on the expression of a suite of genes in the hypothalamic-pituitary-thyroid (HPT) axis via both real time quantitative PCR (qRT-PCR) on whole body extracts and whole mount in situ hybridisation (WISH) to identify tissue targets. The 96-h lethal median concentration (96h-LC50) for TBBPA was 0.9 μM and mortality was preceded by retardation of development (smaller animals) and morphological deformities including, oedemas in the pericardial region and tail, small heads, swollen yolk sac extension. Exposure to BDE-47 did not affect zebrafish embryo-larvae survival at any of the concentrations tested (1 – 100 μM) but caused yolk sac and craniofacial deformities, a curved spine and shorter tail at the highest exposure concentration. TBBPA exposure resulted in higher levels of mRNAs for genes encoding deiodinases (dio1), transport proteins (ttr), the thyroid follicle synthesis protein paired box 8 (pax8) and glucuronidation enzymes (ugt1ab) and lower levels of dio3b mRNAs in whole body extracts, with responses varying with developmental stage. BDE-47 exposure resulted in higher levels of thrb, dio1, dio2, pax8 and ugt1ab mRNAs and lower levels of ttr mRNAs in whole body extracts. TBBPA and BDE-47 therefore appear to disrupt the TH system at multiple levels, increasing TH conjugation and clearance, disrupting thyroid follicle development and altering TH transport. Compensatory responses in TH production/ metabolism by deiodinases were also evident. WISH analyses further revealed that both TBBPA and BDE-47 caused tissue-specific changes in thyroid receptor and deiodinase enzyme expression, with the brain, liver, pronephric ducts and craniofacial tissues appearing particularly responsive to altered TH signalling. Given the important role of TRs in mediating the actions of THs during key developmental processes and deiodinases in the control of peripheral TH levels, these transcriptional alterations may have implications for TH sensitive target genes involved in brain and skeletal development. These findings further highlight the potential vulnerability of the thyroid system to disruption by BFRs during early developmental windows.

Abstract. Full text.

Osborne OJ, Mukaigasa K, Nakajima H, Stolpe B, Romer I, Philips U, Lynch I, Mourabit S, Hirose S, Lead JR, et al (In Press). Sensory systems and ionocytes are targets for silver nanoparticle effects in fish. Nanotoxicology, 10(9), 1276-1286. Abstract. Author URL.

Stevens CH, Croft DP, Paull, Tyler (In Press). Stress and welfare in ornamental fishes: what can be learned from aquaculture?. Jounral of Fish Biology Full text.

Edenbrow M, Bleakley BH, Darden SK, Tyler CR, Ramnarine IW, Croft DP (In Press). The evolution of cooperation: Interacting phenotypes among social partners. The American Naturalist Full text.

Windsor FM, Durance I, Horton AA, Thompson RC, Tyler CR, Ormerod SJ (2019). A catchment-scale perspective of plastic pollution. Glob Chang Biol

Plastic pollution is distributed across the globe, but compared with marine environments, there is only rudimentary understanding of the distribution and effects of plastics in other ecosystems. Here, we review the transport and effects of plastics across terrestrial, freshwater and marine environments. We focus on hydrological catchments as well-defined landscape units that provide an integrating scale at which plastic pollution can be investigated and managed. Diverse processes are responsible for the observed ubiquity of plastic pollution, but sources, fluxes and sinks in river catchments are poorly quantified. Early indications are that rivers are hotspots of plastic pollution, supporting some of the highest recorded concentrations. River systems are also likely pivotal conduits for plastic transport among the terrestrial, floodplain, riparian, benthic and transitional ecosystems with which they connect. Although ecological effects of micro- and nanoplastics might arise through a variety of physical and chemical mechanisms, consensus and understanding of their nature, severity and scale are restricted. Furthermore, while individual-level effects are often graphically represented in public media, knowledge of the extent and severity of the impacts of plastic at population, community and ecosystem levels is limited. Given the potential social, ecological and economic consequences, we call for more comprehensive investigations of plastic pollution in ecosystems to guide effective management action and risk assessment. This is reliant on (a) expanding research to quantify sources, sinks, fluxes and fates of plastics in catchments and transitional waters both independently as a major transport routes to marine ecosystems, (b) improving environmentally relevant dose-response relationships for different organisms and effect pathways, (c) scaling up from studies on individual organisms to populations and ecosystems, where individual effects are shown to cause harm and; (d) improving biomonitoring through developing ecologically relevant metrics based on contemporary plastic research.

Abstract. Author URL.

Nomiri S, Hoshyar R, Ambrosino C, Tyler CR, Mansouri B (2019). A mini review of bisphenol a (BPA) effects on cancer-related cellular signaling pathways. Environmental Science and Pollution Research, 26(9), 8459-8467. Abstract.

Godfray HCJ, Stephens AEA, Jepson PD, Jobling S, Johnson AC, Matthiessen P, Sumpter JP, Tyler CR, McLean AR (2019). A restatement of the natural science evidence base on the effects of endocrine disrupting chemicals on wildlife. Proceedings of the Royal Society B: Biological Sciences, 286(1897). Abstract.

Lee CJ, Paull GC, Tyler CR (2019). Effects of environmental enrichment on survivorship, growth, sex ratio and behaviour in laboratory maintained zebrafish Danio rerio. J Fish Biol, 94(1), 86-95. Abstract. Author URL.

Windsor FM, Tilley RM, Tyler CR, Ormerod SJ (2019). Microplastic ingestion by riverine macroinvertebrates. Science of the Total Environment, 646, 68-74. Abstract.

Mintram KS, Brown AR, Maynard SK, Liu C, Parker SJ, Tyler CR, Thorbek P (2018). Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback. Ecological Modelling, 387, 107-117. Abstract. Full text.

Winter MJ, Windell D, Metz J, Matthews P, Pinion J, Brown JT, Hetheridge MJ, Ball JS, Owen SF, Redfern WS, et al (2018). Author Correction: 4-dimensional functional profiling in the convulsant-treated larval zebrafish brain. Sci Rep, 8(1). Abstract. Author URL.

Lee CJ, Tyler CR, Paull GC (2018). Can simple tank changes benefit the welfare of laboratory zebrafish Danio rerio?. J Fish Biol, 92(3), 653-659. Abstract. Author URL.

David A, Lange A, Tyler CR, Hill EM (2018). Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent. Science of the Total Environment, 621, 782-790. Abstract.

Collison EJ, Hird H, Tyler CR, Cresswell JE (2018). Effects of neonicotinoid exposure on molecular and physiological indicators of honey bee immunocompetence. Apidologie, 49(2), 196-208. Abstract. Full text.

Moreman J, Takesono A, Trznadel M, Winter MJ, Perry A, Wood ME, Rogers NJ, Kudoh T, Tyler CR (2018). Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol a (BPA) and its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish. Environ Sci Technol, 52(11), 6656-6665. Abstract. Author URL.

Orton F, Säfholm M, Jansson E, Carlsson Y, Eriksson A, Fick J, Uren Webster T, McMillan T, Leishman M, Verbruggen B, et al (2018). Exposure to an anti-androgenic herbicide negatively impacts reproductive physiology and fertility in Xenopus tropicalis. Sci Rep, 8(1). Abstract. Author URL. Full text.

Moreman J, Lee O, Trznadel M, David A, Kudoh T, Tyler CR (2017). Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol a and its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae. Environ Sci Technol, 51(21), 12796-12805. Abstract. Author URL.

Bickley LK, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (2017). Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas). ENVIRONMENTAL SCIENCE & TECHNOLOGY, 51(3), 1764-1774. Author URL.

Lange A, Corcoran J, Miyagawa S, Iguchi T, Winter MJ, Tyler CR (2017). Development of a common carp (Cyprinus carpio) pregnane X receptor (cPXR) transactivation reporter assay and its activation by azole fungicides and pharmaceutical chemicals. Toxicol in Vitro, 41, 114-122. Abstract. Author URL. Full text.

Galloway TS, Dogra Y, Garrett N, Rowe D, Tyler CR, Moger J, Lammer E, Landsiedel R, Sauer UG, Scherer G, et al (2017). Ecotoxicological assessment of nanoparticle-containing acrylic copolymer dispersions in fairy shrimp and zebrafish embryos. Environmental Science: Nano, 4(10), 1981-1997. Abstract.

Tohyama S, Ogino Y, Lange A, Myosho T, Kobayashi T, Hirano Y, Yamada G, Sato T, Tatarazako N, Tyler CR, et al (2017). Establishment of estrogen receptor 1 (ESR1)-knockout medaka: ESR1 is dispensable for sexual development and reproduction in medaka, Oryzias latipes. Dev Growth Differ, 59(6), 552-561. Abstract. Author URL.

Uren Webster TM, Williams TD, Katsiadaki I, Lange A, Lewis C, Shears JA, Tyler CR, Santos EM (2017). Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history. Aquat Toxicol, 184, 26-36.

Some fish populations inhabiting contaminated environments show evidence of increased chemical tolerance, however the mechanisms contributing to this tolerance, and whether this is heritable, are poorly understood. We investigated the responses of two populations of wild three-spined stickleback (Gasterosteus aculeatus) with different histories of contaminant exposure to an oestrogen and copper, two widespread aquatic pollutants. Male stickleback originating from two sites, the River Aire, with a history of complex pollution discharges, and Siblyback Lake, with a history of metal contamination, were depurated and then exposed to copper (46μg/L) and the synthetic oestrogen ethinyloestradiol (22ng/L). The hepatic transcriptomic response was compared between the two populations and to a reference population with no known history of exposure (Houghton Springs, Dorset). Gene responses included those typical for both copper and oestrogen, with no discernable difference in response to oestrogen between populations. There was, however, some difference in the magnitude of response to copper between populations. Siblyback fish showed an elevated baseline transcription of genes encoding metallothioneins and a lower level of metallothionein induction following copper exposure, compared to those from the River Aire. Similarly, a further experiment with an F1 generation of Siblyback fish bred in the laboratory found evidence for elevated transcription of genes encoding metallothioneins in unexposed fish, together with an altered transcriptional response to 125μg/L copper, compared with F1 fish originating from the clean reference population exposed to the same copper concentration. These data suggest that the stickleback from Siblyback Lake have a differential response to copper, which is inherited by the F1 generation in laboratory conditions, and for which the underlying mechanism may include an elevation of baseline transcription of genes encoding metallothioneins. The genetic and/or epigenetic mechanisms contributing to this inherited alteration of metallothionein transcription have yet to be established.

Abstract. Author URL. Full text.

Sherman KD, King RA, Dahlgren CP, Simpson SD, Stevens JR, Tyler CR (2017). Historical processes and contemporary anthropogenic activities influence genetic population dynamics of Nassau grouper (Epinephelus striatus) within the Bahamas. Frontiers in Marine Science, 4(DEC). Abstract. Full text.

Bruintjes R, Harding HR, Bunce T, Birch F, Lister J, Spiga I, Benson T, Rossington K, Jones D, Tyler CR, et al (2017). Shipbuilding Docks as Experimental Systems for Realistic Assessments of Anthropogenic Stressors on Marine Organisms. BIOSCIENCE, 67(9), 853-859. Author URL. Full text.

Lillicrap A, Springer T, Tyler CR (2016). A tiered assessment strategy for more effective evaluation of bioaccumulation of chemicals in fish. Regul Toxicol Pharmacol, 75, 20-26. Abstract. Author URL.

Dogra Y, Arkill KP, Elgy C, Stolpe B, Lead J, Valsami-Jones E, Tyler CR, Galloway TS (2016). Cerium oxide nanoparticles induce oxidative stress in the sediment-dwelling amphipod Corophium volutator. Nanotoxicology, 10(4), 480-487. Abstract. Author URL. Full text.

Tohyama S, Miyagawa S, Lange A, Ogino Y, Mizutani T, Ihara M, Tanaka H, Tatarazako N, Kobayashi T, Tyler CR, et al (2016). Evolution of estrogen receptors in ray-finned fish and their comparative responses to estrogenic substances. J Steroid Biochem Mol Biol, 158, 189-197. Abstract. Author URL.

Sherman KD, Dahlgren CP, Stevens JR, Tyler CR (2016). Integrating population biology into conservation management for endangered Nassau grouper Epinephelus striatus. Marine Ecology Progress Series, 554, 263-280. Abstract. Full text.

Collison E, Hird H, Cresswell J, Tyler C (2016). Interactive effects of pesticide exposure and pathogen infection on bee health – a critical analysis. Biological Reviews, 91(4), 1006-1019. Abstract.

Verbruggen B, Bickley LK, van Aerle R, Bateman KS, Stentiford GD, Santos EM, Tyler CR (2016). Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments. Viruses, 8(1). Abstract. Author URL. Full text.

Hamilton PB, Cowx IG, Oleksiak MF, Griffiths AM, Grahn M, Stevens JR, Carvalho GR, Nicol E, Tyler CR (2016). Population-level consequences for wild fish exposed to sublethal concentrations of chemicals – a critical review. Fish and Fisheries, 17(3), 545-566. Abstract.

Song L, Vijver MG, Peijnenburg WJGM, Galloway TS, Tyler CR (2015). A comparative analysis on the in vivo toxicity of copper nanoparticles in three species of freshwater fish. Chemosphere, 139, 181-189. Abstract. Author URL.

Miyagawa S, Lange A, Tohyama S, Ogino Y, Mizutani T, Kobayashi T, Tatarazako N, Tyler CR, Iguchi T (2015). Characterization of Oryzias latipes glucocorticoid receptors and their unique response to progestins. Journal of Applied Toxicology, 35(3), 302-309. Abstract.

Verbruggen B, Bickley LK, Santos EM, Tyler CR, Stentiford GD, Bateman KS, van Aerle R (2015). De novo assembly of the Carcinus maenas transcriptome and characterization of innate immune system pathways. BMC Genomics, 16 Abstract. Author URL. Full text.

Orton F, Tyler CR (2015). Do hormone-modulating chemicals impact on reproduction and development of wild amphibians?. Biol Rev Camb Philos Soc, 90(4), 1100-1117.

Globally, amphibians are undergoing a precipitous decline. At the last estimate in 2004, 32% of the approximately 6000 species were threatened with extinction and 43% were experiencing significant declines. These declines have been linked with a wide range of environmental pressures from habitat loss to climate change, disease and pollution. This review evaluates the evidence that endocrine-disrupting contaminants (EDCs) - pollutants that affect hormone systems - are impacting on wild amphibians and contributing to population declines. The review is limited to anurans (frogs and toads) as data for effects of EDCs on wild urodeles (salamanders, newts) or caecilians (limbless amphibians) are extremely limited. Evidence from laboratory studies has shown that a wide range of chemicals have the ability to alter hormone systems and affect reproductive development and function in anurans, but for the most part only at concentrations exceeding those normally found in natural environments. Exceptions can be found for exposures to the herbicide atrazine and polychlorinated biphenyls in leopard frogs (Rana pipiens) and perchlorate in African clawed frogs (Xenopus laevis). These contaminants induce feminising effects on the male gonads (including 'intersex' - oocytes within testes) at concentrations measured in some aquatic environments. The most extensive data for effects of an EDC in wild amphibian populations are for feminising effects of atrazine on male gonad development in regions across the USA. Even where strong evidence has been provided for feminising effects of EDCs, however, the possible impact of these effects on fertility and breeding outcome has not been established, making inference for effects on populations difficult. Laboratory studies have shown that various chemicals, including perchlorate, polychlorinated biphenyls and bromodiphenylethers, also act as endocrine disrupters through interfering with thyroid-dependent processes that are fundamental for amphibian metamorphosis. Perchlorate has also been shown to induce these effects in wild anuran populations from perchlorate-contaminated environments. Overall, the published data available suggest that some health effects observed in wild anuran populations, most notably intersex, likely have a chemical aetiology; however they derive only from very few anuran species and for a few pesticides at field sites in the USA. To understand better the impacts of EDCs on wild anuran populations, as well as other amphibian groups, assessment of fertility in exposed animals are required. Development of non-destructive biomarkers that are indicative of specific EDC-effect mechanisms are also needed to allow the study of vulnerable populations. This will help to distinguish the effects of EDCs from other environmental and/or genetic influences on development and reproduction.

Abstract. Author URL.

Rolshausen G, Phillip DAT, Beckles DM, Akbari A, Ghoshal S, Hamilton PB, Tyler CR, Scarlett AG, Ramnarine I, Bentzen P, et al (2015). Do stressful conditions make adaptation difficult? Guppies in the oil-polluted environments of southern Trinidad. Evol Appl, 8(9), 854-870. Abstract. Author URL.

Jennings V, Goodhead R, Tyler CR (2015). Ecotoxicology of Nanomaterials in Aquatic Systems. , 8, 3-45. Abstract.

Corcoran J, Winter MJ, Lange A, Cumming R, Owen SF, Tyler CR (2015). Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels. Aquat Toxicol, 161, 127-137. Abstract. Author URL.

Lange A, Sebire M, Rostkowski P, Mizutani T, Miyagawa S, Iguchi T, Hill EM, Tyler CR (2015). Environmental chemicals active as human antiandrogens do not activate a stickleback androgen receptor but enhance a feminising effect of oestrogen in roach. Aquat Toxicol, 168, 48-59.

Sexual disruption is reported in wild fish populations living in freshwaters receiving discharges of wastewater treatment works (WwTW) effluents and is associated primarily with the feminisation of males by exposure to oestrogenic chemicals. Antiandrogens could also contribute to the feminisation of male fish, but there are far less data supporting this hypothesis and almost nothing is known for the effects of oestrogens in combination with antiandrogens in fish. We conducted a series of in vivo exposures in two fish species to investigate the potency on reproductive-relevant endpoints of the antiandrogenic antimicrobials triclosan (TCS), chlorophene (CP) and dichlorophene (DCP) and the resin, abietic acid (AbA), all found widely in WwTW effluents. We also undertook exposures with a mixture of antiandrogens and a mixture of antiandrogens in combination with the oestrogen 17α-ethinyloestradiol (EE2). In stickleback (Gasterosteus aculeatus), DCP showed a tendency to reduce spiggin induction in females androgenised by dihydrotestosterone (DHT), but these findings were not conclusive. In roach (Rutilus rutilus), exposures to DCP (178 days), or a mixture of TCS, CP and AbA (185 days), or to the model antiandrogen flutamide (FL, 178 days) had no effect on gonadal sex ratio or on the development of the reproductive ducts. Exposure to EE2 (1.5ng/L, 185 days) induced feminisation of the ducts in 17% of the males and in the mixture of antiandrogens (TCS, CP, AbA) in combination with EE2, almost all (96%) of the males had a feminised reproductive ducts. In stickleback androgen receptor (ARα and ARβ) transactivation assays, the model antiandrogens, FL and procymidone inhibited 11-ketotestosterone (11-KT) induced receptor activation, but none of the human antiandrogens, TCS, CP, DCP and AbA had an effect. These data indicate that antimicrobial antiandrogens in combination can contribute to the feminisation process in exposed males, but they do not appear to act through the androgen receptor in fish.

Abstract. Author URL.

Pountney A, Filby AL, Thomas GO, Simpson VR, Chadwick EA, Stevens JR, Tyler CR (2015). High liver content of polybrominated diphenyl ether (PBDE) in otters (Lutra lutra) from England and Wales. Chemosphere, 118, 81-86. Abstract. Author URL.

Heindel JJ, Newbold RR, Williams CJ, Iguchi T, Tyler CR (2015). Lou Guillette--in memorandum. Mol Reprod Dev, 82(10), Fmi-v. Author URL.

Goodhead RM, Moger J, Galloway TS, Tyler CR (2015). Tracing engineered nanomaterials in biological tissues using coherent anti-Stokes Raman scattering (CARS) microscopy - a critical review. Nanotoxicology, 9(7), 928-939. Abstract. Author URL.

Lee O, Green JM, Tyler CR (2015). Transgenic fish systems and their application in ecotoxicology. Crit Rev Toxicol, 45(2), 124-141. Abstract. Author URL.

Tohyama S, Miyagawa S, Lange A, Ogino Y, Mizutani T, Tatarazako N, Katsu Y, Ihara M, Tanaka H, Ishibashi H, et al (2015). Understanding the Molecular Basis for Differences in Responses of Fish Estrogen Receptor Subtypes to Environmental Estrogens. Environmental Science and Technology, 49(12), 7439-7447. Abstract.

David A, Abdul-Sada A, Lange A, Tyler CR, Hill EM (2014). A new approach for plasma (xeno)metabolomics based on solid-phase extraction and nanoflow liquid chromatography-nanoelectrospray ionisation mass spectrometry. J Chromatogr A, 1365, 72-85. Abstract. Author URL.

Corcoran J, Lange A, Cumming RI, Owen SF, Ball JS, Tyler CR, Winter MJ (2014). Bioavailability of the imidazole antifungal agent clotrimazole and its effects on key biotransformation genes in the common carp (Cyprinus carpio). Aquat Toxicol, 152, 57-65.

Clotrimazole (CTZ) is a persistent imidazole antifungal agent which is frequently detected in the aquatic environment and predicted to bio-concentrate in fish. Common carp (Cyprinus carpio) were exposed to mean measured concentrations of either 1.02 or 14.63μgl(-1) CTZ for 4 and 10 days, followed by a depuration period of 4 days in a further group of animals. Following each exposure regimen, plasma and liver CTZ concentrations were measured. Mean measured plasma concentrations of CTZ in animals exposed to the lower concentration of CTZ were 30 and 44μgl(-1) on days 4 and 10, respectively, and in the higher concentration were 318 and 336μgl(-1). Mean measured liver levels in the same animals were 514, 1725, 2111 and 7017μgl(-1) suggesting progressive hepatic accumulation. Measurement of CTZ in plasma after depuration suggested efficient elimination within 4 days, but appreciable levels of CTZ remained in the liver after depuration suggesting a degree of persistence in this tissue. In addition we measured responses of a number of key hepatic detoxification gene targets in the liver associated with the transcription factor pregnane X receptor (PXR); namely cyp450s 2k and 3a, glutathione-S-transferases a and p (gsta and p), and drug transporters multidrug resistance protein1 (mdr1), and MDR-related protein2 (mrp2). CTZ is a potent ligand of the PXR in humans and there is some evidence of PXR activation following exposure to CTZ in fish. The highest concentration of CTZ was adopted to explore the potential for alterations to detoxification gene expression in fish at a pharmacologically relevant dose level, and the lower concentration is within the range reported in effluents from waste water treatment works (WWTW). The genes for all biotransformation enzymes were up-regulated after exposure to the higher concentration of CTZ for 10 days, and alterations in expression occurred for the drug transporter genes mdr1 and mrp2 following exposure to the lower concentration of 1.02μgl(-1) CTZ (mean measured concentration). These data support the potential for CTZ to induce alterations in biotransformation and drug transporter genes associated with PXR in fish at concentrations measured in some WWTW effluents.

Abstract. Author URL.

Miyagawa S, Lange A, Tohyama S, Ogino Y, Mizutani T, Kobayashi T, Tatarazako N, Tyler CR, Iguchi T (2014). Characterization of Oryzias latipes glucocorticoid receptors and their unique response to progestins. Journal of Applied Toxicology

Morrissey CA, Stanton DW, Tyler CR, Pereira MG, Newton J, Durance I, Ormerod SJ (2014). Developmental impairment in eurasian dipper nestlings exposed to urban stream pollutants. Environmental Toxicology and Chemistry

Morrissey CA, Stanton DWG, Tyler CR, Pereira MG, Newton J, Durance I, Ormerod SJ (2014). Developmental impairment in eurasian dipper nestlings exposed to urban stream pollutants. Environmental Toxicology and Chemistry, 33(6), 1315-1323. Abstract.

Miyagawa S, Lange A, Hirakawa I, Tohyama S, Ogino Y, Mizutani T, Kagami Y, Kusano T, Ihara M, Tanaka H, et al (2014). Differing species responsiveness of estrogenic contaminants in fish is conferred by the ligand binding domain of the estrogen receptor. Environmental Science and Technology, 48(9), 5254-5263. Abstract.

Southam AD, Lange A, Al-Salhi R, Hill EM, Tyler CR, Viant MR (2014). Distinguishing between the metabolome and xenobiotic exposome in environmental field samples analysed by direct-infusion mass spectrometry based metabolomics and lipidomics. Metabolomics, 10(6), 1050-1058. Abstract. Author URL.

Kermorgant M, Lancien F, Mimassi N, Tyler CR, Le Mével J-C (2014). Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory functions in rainbow trout (Oncorhynchus mykiss). Gen Comp Endocrinol, 205, 176-184. Abstract. Author URL.

Baker TJ, Tyler CR, Galloway TS (2014). Impacts of metal and metal oxide nanoparticles on marine organisms. Environmental Pollution, 186, 257-271. Abstract.

Baker TJ, Tyler CR, Galloway TS (2014). Impacts of metal and metal oxide nanoparticles on marine organisms. Environ Pollut, 186, 257-271. Abstract. Author URL.

Hazlerigg CRE, Tyler CR, Lorenzen K, Wheeler JR, Thorbek P (2014). Population relevance of toxicant mediated changes in sex ratio in fish: an assessment using an individual-based zebrafish (Danio rerio) model. Ecological Modelling

Ecological risk assessments (ERAs) of toxicants are predominantly based on data from laboratory tests on individuals. However, the protection goal is generally at the population level. Ecological modelling has the potential to link individual-level effects to population-level outcomes. Here we developed an individual-based zebrafish population model to study the possible population-level relevance of toxicant-mediated changes in sex ratio. The model was structured with sub-models based on empirical data (e.g. growth, reproduction, mortality) derived from a combination of our own laboratory and field experiments, the literature and theoretical concepts. The outputs of the default model were validated against size distributions for wild populations of zebrafish sampled in Bangladesh. Sensitivity analysis showed that population abundance was most sensitive to changes in density-dependent survival and the availability of refugia for juveniles.The model was then used to determine the population-level relevance of changes in sex ratio caused by an androgenic (dihydrotestosterone) and oestrogenic (4-tert-octylphenol) substance. Both were investigated under acute (10 day) and chronic (1 year) exposure regimes. Acute exposures to the test chemicals had little effect on population-level endpoints at any of the concentrations tested. Chronic exposures decreased population abundance at higher concentrations for both chemicals and most strongly with DHT. However, these concentrations were far in excess of environmentally realistic levels. Our study demonstrated that ecological models can be applied to link laboratory derived ecotoxicity data at the individual level to impacts at the population level and in our study we found different modes of action and potencies caused different levels of population perturbation. Ecological models can therefore help in assessing the ecological relevance of different organism-level effects of toxicants aiding future environmental protection strategies. © 2014 Elsevier B.V.

Abstract.

Hamilton PB, Nicol E, De-Bastos ESR, Williams RJ, Sumpter JP, Jobling S, Stevens JR, Tyler CR (2014). Populations of a cyprinid fish are self-sustaining despite widespread feminization of males. BMC Biol, 12 Abstract. Author URL. Full text.

Filby AL, Ortiz-Zarragoitia M, Tyler CR (2014). The vas:: Egfp transgenic zebrafish: a practical model for studies on the molecular mechanisms by which environmental estrogens affect gonadal sex differentiation. Environmental Toxicology and Chemistry, 33(3), 602-605. Abstract.

Filby AL, Ortiz-Zarragoitia M, Tyler CR (2014). The vas::egfp transgenic zebrafish: a practical model for studies on the molecular mechanisms by which environmental estrogens affect gonadal sex differentiation. Environ Toxicol Chem, 33(3), 602-605. Abstract. Author URL.

Watts AJR, Lewis C, Goodhead RM, Beckett SJ, Moger J, Tyler CR, Galloway TS (2014). Uptake and retention of microplastics by the shore crab Carcinus maenas. Environ Sci Technol, 48(15), 8823-8830. Abstract. Author URL.

Katsu Y, Lange A, Miyagawa S, Urushitani H, Tatarazako N, Kawashima Y, Tyler CR, Iguchi T (2013). Cloning, expression and functional characterization of carp, cyprinus carpio, estrogen receptors and their differential activations by estrogens. Journal of Applied Toxicology, 33(1), 41-49.

Sex-steroid hormones are essential for normal reproductive activity in both sexes. Estrogens are necessary for ovarian differentiation during a critical developmental stage in vertebrates and promote the growth and differentiation of the female reproductive system. Importantly, environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. To understand the molecular mechanisms of estrogen actions and to evaluate estrogen receptor ligand interactions in the carp, Cyprinus carpio, a species used widely for both field- and laboratory-based studies, we cloned all three carp estrogen receptors (ER; ERα, ERβ1 and ERβ2) and applied an estrogen-responsive (ERE)-luciferase reporter assay system to characterize the interactions of these receptors with steroidal and synthetic estrogens. DNA fragments encoding all three ERs in carp, ERα, ERβ1 and ERβ2, were obtained from the ovary using degenerate primer sets and PCR techniques, and full-length carp ER (cER) cDNAs were then obtained using RACE (rapid amplification of the cDNA end) techniques. Amino acid sequences of cERs showed overall homology of 46% (α vs β1), 49% (α vs β2) and 53% (β1 vs β2). In the transient transfection ERE-luciferase reporter assay system (using mammalian cells) the cER proteins displayed estrogen-dependent activation of transcription and cERβ2 showed a higher sensitivity to the natural steroid oestrogen, 17β-estradiol, than cERα. The assay system developed is a powerful assay for toxicology and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen-disrupting mechanisms in carp. The data presented also expand our knowledge of estrogen receptor evolution. Copyright © 2011 John Wiley & Sons, Ltd. Environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. We cloned all three carp Cyprinus carpio, estrogen receptors [ER; ERa, ERb1 and ERb2] and applied a transient transfection ERE-luciferase reporter assay system using mammalian cells. cERb2 showed a higher sensitivity to the natural steroid oestrogen, 17b-estradiol, than cERa. This is a powerful assay for toxicology, and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen disrupting mechanisms in carp. © 2011 John Wiley & Sons, Ltd.

Abstract.

Ankley GT, Tyler CR (2013). Development of methods to detect occurrence and effects of endocrine-disrupting chemicals: Fueling a fundamental shift in regulatory ecotoxicology. Environmental Toxicology and Chemistry, 32(12), 2661-2662.

Osborne OJ, Johnston BD, Moger J, Balousha M, Lead JR, Kudoh T, Tyler CR (2013). Effects of particle size and coating on nanoscale Ag and TiO₂ exposure in zebrafish (Danio rerio) embryos. Nanotoxicology, 7(8), 1315-1324. Abstract. Author URL.

Hawkes LA, McGowan A, Godley BJ, Gore S, Lange A, Tyler CR, Wheatley D, White J, Witt MJ, Broderick AC, et al (2013). Estimating sex ratios in Caribbean hawksbill turtles: Testosterone levels and climate effects. Aquatic Biology, 18(1), 9-19. Abstract.

Morrissey CA, Stanton DWG, Pereira MG, Newton J, Durance I, Tyler CR, Ormerod SJ (2013). Eurasian dipper eggs indicate elevated organohalogenated contaminants in urban rivers. Environmental Science and Technology, 47(15), 8931-8939. Abstract.

Segner H, Casanova-Nakayama A, Kase R, Tyler CR (2013). Impact of environmental estrogens on Yfish considering the diversity of estrogen signaling. General and Comparative Endocrinology, 191, 190-201.

Research on endocrine disruption in fish has been dominated by studies on estrogen-active compounds which act as mimics of the natural estrogen, 17β-estradiol (E2), and generally exert their biological actions by binding to and activation of estrogen receptors (ERs). Estrogens play central roles in reproductive physiology and regulate (female) sexual differentiation. In line with this, most adverse effects reported for fish exposed to environmental estrogens relate to sexual differentiation and reproduction. E2, however, utilizes a variety of signaling mechanisms, has multifaceted functions and targets, and therefore the toxicological and ecological effects of environmental estrogens in fish will extend beyond those associated with the reproduction. This review first describes the diversity of estrogen receptor signaling in fish, including both genomic and non-genomic mechanisms, and receptor crosstalk. It then considers the range of non-reproductive physiological processes in fish that are known to be responsive to estrogens, including sensory systems, the brain, the immune system, growth, specifically through the growth hormone/insulin-like growth factor system, and osmoregulation. The diversity in estrogen responses between fish species is then addressed, framed within evolutionary and ecological contexts, and we make assessments on their relevance for toxicological sensitivity as well as ecological vulnerability. The diversity of estrogen actions raises questions whether current risk assessment strategies, which focus on reproductive endpoints, and a few model fish species only, are protective of the wider potential health effects of estrogens. Available - although limited - evidence nevertheless suggests that quantitative environmental threshold concentrations for environmental protection derived from reproductive tests with model fish species are protective for non-reproductive effects as well. The diversity of actions of estrogens across divergent physiological systems, however, may lead to and underestimation of impacts on fish populations as their effects are generally considered on one functional process only and this may underrepresent the impact on the different physiological processes collectively. © 2013 Elsevier Inc.

Abstract.

Bickley LK, Brown AR, Hosken DJ, Hamilton PB, Le Page G, Paull GC, Owen SF, Tyler CR (2013). Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish. Evolutionary Applications, 6(2), 279-289. Abstract. Full text.

van Aerle R, Lange A, Moorhouse A, Paszkiewicz K, Ball K, Johnston BD, de-Bastos E, Booth T, Tyler CR, Santos EM, et al (2013). Molecular mechanisms of toxicity of silver nanoparticles in zebrafish embryos. Environ Sci Technol, 47(14), 8005-8014. Abstract. Author URL. Full text.

Santos EM, Hamilton PB, Coe TS, Ball JS, Cook AC, Katsiadaki I, Tyler CR (2013). Population bottlenecks, genetic diversity and breeding ability of the three-spined stickleback (Gasterosteus aculeatus) from three polluted English Rivers. Aquatic Toxicology, 142-143, 264-271. Abstract.

Bergman A, Andersson AM, Becher G, Van Den Berg M, Blumberg B, Bjerregaard P, Bornehag CG, Bornman R, Brandt I, Brian JV, et al (2013). Science and policy on endocrine disrupters must not be mixed: a reply to a "common sense" intervention by toxicology journal editors. Environmental Health: a Global Access Science Source, 12(1). Abstract.

Lee OH, Takesono A, Tada M, Tyler CR, Kudoh T (2012). Biosensor zebrafish provide new insights into potential health effects of environmental estrogens. Environ Health Perspect, 120, 990-996. Full text.

Baalousha M, Ju-Nam Y, Cole PA, Gaiser B, Fernandes TF, Hriljac JA, Jepson MA, Stone V, Tyler CR, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-Part 1: Size measurements. Environmental Toxicology and Chemistry, 31(5), 983-993. Abstract.

Baalousha M, Ju-Nam Y, Cole PA, Hriljac JA, Jones IP, Tyler CR, Stone V, Fernandes TF, Jepson MA, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-Part 2: Nonsize measurements. Environmental Toxicology and Chemistry, 31(5), 994-1003. Abstract.

Baalousha M, Ju-Nam Y, Cole PA, Hriljac JA, Jones IP, Tyler CR, Stone V, Fernandes TF, Jepson MA, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-Part 2: Nonsize measurements. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 31(5), 994-1003. Author URL.

Baalousha M, Ju-Nam Y, Cole PA, Gaiser B, Fernandes TF, Hriljac JA, Jepson MA, Stone V, Tyler CR, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-part 1: Size measurements. Environmental Toxicology and Chemistry

Baalousha M, Ju-Nam Y, Cole PA, Hriljac JA, Jones IP, Tyler CR, Stone V, Fernandes TF, Jepson MA, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-part 2: Nonsize measurements. Environmental Toxicology and Chemistry

Katsu Y, Lange A, Miyagawa S, Urushitani H, Tatarazako N, Kawashima CR, Iguchi T (2012). Cloning, expression and functional characterization of carp, Cyprinus carpio, estrogen receptors and their differential activations by estrogens. Journal of Applied Toxicology Abstract.

Söffker M, Stevens JR, Tyler CR (2012). Comparative breeding and behavioral responses to ethinylestradiol exposure in wild and laboratory maintained zebrafish (Danio rerio) populations. Environ Sci Technol, 46(20), 11377-11383. Abstract. Author URL.

Lange A, Katsu Y, Miyagawa S, Ogino Y, Urushitani H, Kobayashi T, Hirai T, Shears JA, Nagae M, Yamamoto J, et al (2012). Comparative responsiveness to natural and synthetic estrogens of fish species commonly used in the laboratory and field monitoring. Aquat Toxicol, 109, 250-258. Abstract. Author URL.

Hazlerigg CRE, Lorenzen K, Thorbek P, Wheeler JR, Tyler CR (2012). Density-dependent processes in the life history of fishes: Evidence from laboratory populations of zebrafish Danio rerio. PLoS ONE, 7(5). Abstract.

Lee O, Tyler CR, Kudoh T (2012). Development of a transient expression assay for detecting environmental oestrogens in zebrafish and medaka embryos. BMC Biotechnol, 12

BACKGROUND: Oestrogenic contaminants are widespread in the aquatic environment and have been shown to induce adverse effects in both wildlife (most notably in fish) and humans, raising international concern. Available detecting and testing systems are limited in their capacity to elucidate oestrogen signalling pathways and physiological impacts. Here we developed a transient expression assay to investigate the effects of oestrogenic chemicals in fish early life stages and to identify target organs for oestrogenic effects. To enhance the response sensitivity to oestrogen, we adopted the use of multiple tandem oestrogen responsive elements (EREc38) in a Tol2 transposon mediated Gal4ff-UAS system. The plasmid constructed (pTol2_ERE-TATA-Gal4ff), contains three copies of oestrogen response elements (3ERE) that on exposure to oestrogen induces expression of Gal4ff which this in turn binds Gal4-responsive Upstream Activated Sequence (UAS) elements, driving the expression of a second reporter gene, EGFP (Enhanced Green Fluorescent Protein). RESULTS: the response of our construct to oestrogen exposure in zebrafish embryos was examined using a transient expression assay. The two plasmids were injected into 1-2 cell staged zebrafish embryos, and the embryos were exposed to various oestrogens including the natural steroid oestrogen 17ß-oestradiol (E2), the synthetic oestrogen 17α- ethinyloestradiol (EE2), and the relatively weak environmental oestrogen nonylphenol (NP), and GFP expression was examined in the subsequent embryos using fluorescent microscopy. There was no GFP expression detected in unexposed embryos, but specific and mosaic expression of GFP was detected in the liver, heart, somite muscle and some other tissue cells for exposures to steroid oestrogen treatments (EE2; 10 ng/L, E2; 100 ng/L, after 72 h exposures). For the NP exposures, GFP expression was observed at 10 μg NP/L after 72 h (100 μg NP/L was toxic to the fish). We also demonstrate that our construct works in medaka, another model fish test species, suggesting the transient assay is applicable for testing oestrogenic chemicals in fish generally. CONCLUSION: Our results indicate that the transient expression assay system can be used as a rapid integrated testing system for environmental oestrogens and to detect the oestrogenic target sites in developing fish embryos.

Abstract. Author URL. Full text.

Brown AR, Bickley LK, Ryan TA, Paull GC, Hamilton PB, Owen SF, Sharpe AD, Tyler CR (2012). Differences in sexual development in inbred and outbred zebrafish (Danio rerio) and implications for chemical testing. Aquat Toxicol, 112-113, 27-38. Abstract. Author URL.

Cresswell JE, Page CJ, Uygun MB, Holmbergh M, Li Y, Wheeler JG, Laycock I, Pook CJ, de Ibarra NH, Smirnoff N, et al (2012). Differential sensitivity of honey bees and bumble bees to a dietary insecticide (imidacloprid). Zoology, 115(6), 365-371. Abstract.

Corcoran J, Lange A, Winter MJ, Tyler CR (2012). Effects of Pharmaceuticals on the Expression of Genes Involved in Detoxification in a Carp Primary Hepatocyte Model. Environmental Science and Technology, 46(11), 6306-6314. Abstract.

Söffker M, Tyler CR (2012). Endocrine disrupting chemicals and sexual behaviors in fish--a critical review on effects and possible consequences. Crit Rev Toxicol, 42(8), 653-668. Abstract. Author URL.

Filby AL, Paull GC, Searle F, Ortiz-Zarragoitia M, Tyler CR (2012). Environmental estrogen-induced alterations of male aggression and dominance hierarchies in fish: a mechanistic analysis. Environ Sci Technol, 46(6), 3472-3479. Abstract. Author URL.

Gaiser BK, Fernandes TF, Jepson MA, Lead JR, Tyler CR, Baalousha M, Biswas A, Britton GJ, Cole PA, Johnston BD, et al (2012). Interspecies comparisons on the uptake and toxicity of silver and cerium dioxide nanoparticles. Environmental Toxicology and Chemistry, 31(1), 144-154. Abstract.

Fabrega J, Tantra R, Amer A, Stolpe B, Tomkins J, Fry T, Lead JR, Tyler CR, Galloway TS (2012). Sequestration of zinc from zinc oxide nanoparticles and life cycle effects in the sediment dweller amphipod Corophium volutator. Environ Sci Technol, 46(2), 1128-1135. Abstract. Author URL.

Croft DP, Hamilton PB, Darden SK, Jacoby DMP, James R, Bettaney EM, Tyler CR (2012). The role of relatedness in structuring the social network of a wild guppy population. Oecologia, 170(4), 955-963. Abstract.

Croft DP, Hamilton PB, Darden SK, Jacoby DMP, James R, Bettaney EM, Tyler CR (2012). The role of relatedness in structuring the social network of a wild guppy population. Oecologia, 1-9.

Al-Salhi R, Abdul-Sada A, Lange A, Tyler CR, Hill EM (2012). The xenometabolome and novel contaminant markers in fish exposed to a wastewater treatment works effluent. Environmental Science and Technology, 46(16), 9080-9088. Abstract.

Larner F, Dogra Y, Dybowska A, Fabrega J, Stolpe B, Bridgestock LJ, Goodhead R, Weiss DJ, Moger J, Lead JR, et al (2012). Tracing bioavailability of ZnO nanoparticles using stable isotope labeling. Environ Sci Technol, 46(21), 12137-12145. Abstract. Author URL.

Brown AR, Bickley LK, Le Page G, Hosken DJ, Paull GC, Hamilton PB, Owen SF, Robinson J, Sharpe AD, Tyler CR, et al (2011). Are toxicological responses in laboratory (inbred) zebrafish representative of those in outbred (wild) populations? - a case study with an endocrine disrupting chemical. Environ Sci Technol, 45(9), 4166-4172. Abstract. Author URL.

Rostkowski P, Horwood J, Shears JA, Lange A, Oladapo FO, Besselink HT, Tyler CR, Hill EM (2011). Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. Environmental Science and Technology, 45(24), 10660-10667. Abstract.

Gaiser BK, Biswas A, Rosenkranz P, Jepson MA, Lead JR, Stone V, Tyler CR, Fernandes TF (2011). Effects of silver and cerium dioxide micro- and nano-sized particles on Daphnia magna. Journal of Environmental Monitoring, 13(5), 1227-1235. Abstract.

Lange A, Paull GC, Hamilton PB, Iguchi T, Tyler CR (2011). Implications of persistent exposure to treated wastewater effluent for breeding in wild roach (Rutilus rutilus) populations. Environ Sci Technol, 45(4), 1673-1679. Abstract. Author URL.

García-López Á, Sánchez-Amaya MI, Tyler CR, Prat F (2011). Mechanisms of oocyte development in European sea bass (Dicentrarchus labrax L.): investigations via application of unilateral ovariectomy. Reproduction, 142(2), 243-253. Abstract. Author URL.

Southam AD, Lange A, Hines A, Hill EM, Katsu Y, Iguchi T, Tyler CR, Viant MR (2011). Metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (Rutilus rutilus): Implications for biomonitoring. Environmental Science and Technology, 45(8), 3759-3767. Abstract.

Sebire M, Katsiadaki I, Taylor NGH, Maack G, Tyler CR (2011). Short-term exposure to a treated sewage effluent alters reproductive behaviour in the three-spined stickleback (Gasterosteus aculeatus). Aquat Toxicol, 105(1-2), 78-88. Abstract. Author URL.

Fabrega J, Luoma SN, Tyler CR, Galloway TS, Lead JR (2011). Silver nanoparticles: behaviour and effects in the aquatic environment. Environ Int, 37(2), 517-531. Abstract. Author URL.

Harris CA, Hamilton PB, Runnalls TJ, Vinciotti V, Henshaw A, Hodgson D, Coe TS, Jobling S, Tyler CR, Sumpter JP, et al (2011). The consequences of feminization in breeding groups of wild fish. Environ Health Perspect, 119(3), 306-311. Abstract. Author URL. Full text.

Scown TM, Goodhead RM, Johnston BD, Moger J, Baalousha M, Lead JR, Van Aerle R, Iguchi T, Tyler CR (2010). Assessment of cultured fish hepatocytes for studying cellular uptake and (eco)toxicity of nanoparticles. Environmental Chemistry, 7(1), 36-49. Abstract.

Johnston BD, Scown TM, Moger J, Cumberland SA, Baalousha M, Linge K, van Aerle R, Jarvis K, Lead JR, Tyler CR, et al (2010). Bioavailability of nanoscale metal oxides TiO(2), CeO(2), and ZnO to fish. Environ Sci Technol, 44(3), 1144-1151. Abstract. Author URL. Full text.

Paull GC, Filby AL, Giddins HG, Coe TS, Hamilton PB, Tyler CR (2010). Dominance hierarchies in zebrafish (Danio rerio) and their relationship with reproductive success. Zebrafish, 7(1), 109-117. Abstract. Author URL.

Panter GH, Hutchinson TH, Hurd KS, Bamforth J, Stanley RD, Wheeler JR, Tyler CR (2010). Effects of a weak oestrogenic active chemical (4-tert-pentylphenol) on pair-breeding and F1 development in the fathead minnow (Pimephales promelas). Aquatic Toxicology, 97(4), 314-323.

A fish full life-cycle (FFLC) is the most comprehensive test to determine reproductive toxicity of chemicals to fish and this is likely to apply equally to endocrine active chemicals (EACs). However, FFLC tests use large numbers of animals, are expensive and time consuming. Alternative chronic tests, to the FFLC, potentially include sensitive life-stage windows of effect, such as sexual differentiation, early gonadal development and reproduction. In this paper, a fish pair-breeding study was applied to assess the biological effects of a weak environmental oestrogen, 4-tert-pentylphenol (4TPP), on reproduction and subsequent development of the F1 generation. The results of this study were then compared with the results for a published FFLC study, with this chemical. Fathead minnows (Pimephales promelas) were held in pairs and their reproductive performance assessed over two concurrent 21-day periods, the first without exposure to the test chemical, followed by the second with exposure to the test chemical, in a flow-through system at 25 ± 1 °C. Embryos from two pairs, per treatment, were subsequently grown up in clean water until 90 days post-hatch to assess developmental effects of the parental exposure on the F1 generation. Nominal (measured geometric mean, time weighted) test concentrations of 4TPP were 56 (48), 180 (173) and 560 (570) μg l-1. A significant decrease in fecundity was observed in all 4TPP exposed fish (mean number of eggs spawned per pair and number of spawns per pair) when compared to the solvent control. Vitellogenin (VTG) was significantly elevated in F0 males exposed to 560 μg 4TPP l-1. Somatic endpoints, secondary sexual characteristics (SSC) and gonadosomatic index (GSI) were not affected by the 4TPP exposure. In the F1 generation, there were no treatment-related effects on hatching success, survival, growth, SSC or GSI. Histological examination of the gonads of the F1 fish revealed no treatment-related effects on sex ratio, sexual differentiation or sexual development. However, plasma VTG concentrations were significantly elevated in F1 male fish, derived from parents that had previously been exposed to 4TPP at concentrations of ≥180 μg l-1. These data show that the reproductive performance test is suitable for detecting weak environmental oestrogenic chemicals and that exposure of adult fish to oestrogens can result in altered biomarker expression (VTG) of the F1 generation. Our findings indicate that the reproductive performance test was as sensitive for detecting effects on reproduction when compared with a published FFLC test for 4TPP. © 2010 Elsevier B.V. All rights reserved.

Abstract.

Filby AL, Shears JA, Drage BE, Churchley JH, Tyler CR (2010). Effects of advanced treatments of wastewater effluents on estrogenic and reproductive health impacts in fish. Environ Sci Technol, 44(11), 4348-4354. Abstract. Author URL.

Scown TM, Santos EM, Johnston BD, Gaiser B, Baalousha M, Mitov S, Lead JR, Stone V, Fernandes TF, Jepson M, et al (2010). Effects of aqueous exposure to silver nanoparticles of different sizes in rainbow trout. Toxicol Sci, 115(2), 521-534. Abstract. Author URL.

Fenlon KA, Johnson AC, Tyler CR, Hill EM (2010). Gas-liquid chromatography-tandem mass spectrometry methodology for the quantitation of estrogenic contaminants in bile of fish exposed to wastewater treatment works effluents and from wild populations. Journal of Chromatography A, 1217(1), 112-118.

Fish can be exposed to a complex mixture of chemical contaminants arising from the exposure to wastewater treatment works (WwTWs) effluents. Some of these contaminants are estrogenic and have been associated with feminisation of male fish and the presence of populations containing intersex individuals. However the detection of trace levels (ng/L) of estrogenic chemicals surface waters can be difficult and does not give information on the exposure of aquatic organisms to these contaminants. In this study we assessed whether the analysis of estrogenic substances that bioconcentrate in fish bile can be used to detect the exposure of fish to feminising contaminants in receiving waters and effluents, and thus facilitate their monitoring of these substances in aquatic environments. Estrogenic metabolites in bile were deconjugated using enzymatic hydrolysis and partially purified by solid phase extraction. Steroidal and xenoestrogens were derivatized to their trimethylsilyl ethers and quantified by gas-liquid chromatography-mass spectrometry (GC-MS/MS) using multiple reaction monitoring. The method was validated using spiked bile samples from immature female rainbow trout (Oncorhynchus mykiss) as well as bile from sexually mature roach (Rutilus rutilus) that had been exposed to either tap water or an undiluted estrogenic effluent for 10 days or captured from a river site downstream of a WwTWs effluent discharge. The mean recovery of target analytes from spiked bile was between 86 and 99% and the limit of detection was between 0.1 and 0.7 ng/mL bile for bisphenol a (BPA), 17β-estradiol (E2), estrone (E1) and 17α-ethinylestradiol (EE2), and 11, 60 and 327 ng/mL bile for branched nonyl chain isomeric mixtures of 4-nonylphenolethoxylate (NP1EO), 4-nonylphenol (NP) and 4-nonylphenoldiethoxylate (NP2EO), respectively. All target analytes were detected in bile from roach exposed directly to a WwTWs effluent, with concentrations between 6-13 μg/mL bile for NP, 18-21 μg/mL for NP1EO, 75-135 μg/mL for NP2EO, 0.7-2.5 μg/mL for BPA, E2 and E1 and 17-29 ng/mL for EE2. With the exception of NP2EO, all analytes were detected in at least 2 out of the 5 fish sampled from the River Thames. BPA and NP1EO were detected in all three reference fish held in tap water indicating possible contamination from laboratory plastics. The work shows that analysis of 20-100 μL quantities of bile could be a useful approach in detecting exposure to mixtures of estrogenic contaminants taken up by fish from WwTW effluents and has the potential for monitoring the efficacy of remediation strategies that may be adopted for reduction of these endocrine disrupting chemicals in the aquatic environment. © 2009 Elsevier B.V. All rights reserved.

Abstract.

Katsiadaki I, Williams TD, Ball JS, Bean TP, Sanders MB, Wu H, Santos EM, Brown MM, Baker P, Ortega F, et al (2010). Hepatic transcriptomic and metabolomic responses in the Stickleback (Gasterosteus aculeatus) exposed to ethinyl-estradiol. Aquat Toxicol, 97(3), 174-187. Abstract. Author URL.

Santos EM, Ball JS, Williams TD, Wu H, Ortega F, van Aerle R, Katsiadaki I, Falciani F, Viant MR, Chipman JK, et al (2010). Identifying health impacts of exposure to copper using transcriptomics and metabolomics in a fish model. Environ Sci Technol, 44(2), 820-826. Abstract. Author URL.

Coe TS, Söffker MK, Filby AL, Hodgson D, Tyler CR (2010). Impacts of early life exposure to estrogen on subsequent breeding behavior and reproductive success in zebrafish. Environ Sci Technol, 44(16), 6481-6487. Abstract. Author URL.

Van Aggelen G, Ankley GT, Baldwin WS, Bearden DW, Benson WH, Chipman JK, Collette TW, Craft JA, Denslow ND, Embry MR, et al (2010). Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring: hurdles, achievements, and future outlook. Environ Health Perspect, 118(1), 1-5. Abstract. Author URL.

Corcoran J, Winter MJ, Tyler CR (2010). Pharmaceuticals in the aquatic environment: a critical review of the evidence for health effects in fish. Crit Rev Toxicol, 40(4), 287-304. Abstract. Author URL.

Filby AL, Paull GC, Bartlett EJ, Van Look KJW, Tyler CR (2010). Physiological and health consequences of social status in zebrafish (Danio rerio). Physiol Behav, 101(5), 576-587. Abstract. Author URL.

Hill EM, Evans KL, Horwood J, Rostkowski P, Oladapo FO, Gibson R, Shears JA, Tyler CR (2010). Profiles and some initial identifications of (anti)androgenic compounds in fish exposed to wastewater treatment works effluents. Environ Sci Technol, 44(3), 1137-1143. Abstract. Author URL.

Scown TM, van Aerle R, Tyler CR (2010). Review: Do engineered nanoparticles pose a significant threat to the aquatic environment?. Crit Rev Toxicol, 40(7), 653-670. Abstract. Author URL.

Filby AL, Paull GC, Hickmore TF, Tyler CR (2010). Unravelling the neurophysiological basis of aggression in a fish model. BMC Genomics, 11

BACKGROUND: Aggression is a near-universal behaviour with substantial influence on and implications for human and animal social systems. The neurophysiological basis of aggression is, however, poorly understood in all species and approaches adopted to study this complex behaviour have often been oversimplified. We applied targeted expression profiling on 40 genes, spanning eight neurological pathways and in four distinct regions of the brain, in combination with behavioural observations and pharmacological manipulations, to screen for regulatory pathways of aggression in the zebrafish (Danio rerio), an animal model in which social rank and aggressiveness tightly correlate. RESULTS: Substantial differences occurred in gene expression profiles between dominant and subordinate males associated with phenotypic differences in aggressiveness and, for the chosen gene set, they occurred mainly in the hypothalamus and telencephalon. The patterns of differentially-expressed genes implied multifactorial control of aggression in zebrafish, including the hypothalamo-neurohypophysial-system, serotonin, somatostatin, dopamine, hypothalamo-pituitary-interrenal, hypothalamo-pituitary-gonadal and histamine pathways, and the latter is a novel finding outside mammals. Pharmacological manipulations of various nodes within the hypothalamo-neurohypophysial-system and serotonin pathways supported their functional involvement. We also observed differences in expression profiles in the brains of dominant versus subordinate females that suggested sex-conserved control of aggression. For example, in the HNS pathway, the gene encoding arginine vasotocin (AVT), previously believed specific to male behaviours, was amongst those genes most associated with aggression, and AVT inhibited dominant female aggression, as in males. However, sex-specific differences in the expression profiles also occurred, including differences in aggression-associated tryptophan hydroxylases and estrogen receptors. CONCLUSIONS: Thus, through an integrated approach, combining gene expression profiling, behavioural analyses, and pharmacological manipulations, we identified candidate genes and pathways that appear to play significant roles in regulating aggression in fish. Many of these are novel for non-mammalian systems. We further present a validated system for advancing our understanding of the mechanistic underpinnings of complex behaviours using a fish model.

Abstract. Author URL.

Mehinto AC, Hill EM, Tyler CR (2010). Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss). Environ Sci Technol, 44(6), 2176-2182. Abstract. Author URL.

Oehlmann J, Schulte-Oehlmann U, Kloas W, Jagnytsch O, Lutz I, Kusk KO, Wollenberger L, Santos EM, Paull GC, VanLook KJW, et al (2009). A critical analysis of the biological impacts of plasticizers on wildlife. Philosophical Transactions of the Royal Society B: Biological Sciences, 364(1526), 2047-2062. Abstract.

Tyler CR, Filby AL, Bickley LK, Cumming RI, Gibson R, Labadie P, Katsu Y, Liney KE, Shears JA, Silva-Castro V, et al (2009). Environmental health impacts of equine estrogens derived from hormone replacement therapy. Environ Sci Technol, 43(10), 3897-3904. Abstract. Author URL.

Thorpe KL, Maack G, Benstead R, Tyler CR (2009). Estrogenic wastewater treatment works effluents reduce egg production in fish. Environ Sci Technol, 43(8), 2976-2982. Abstract. Author URL.

Bickley LK, Lange A, Winter MJ, Tyler CR (2009). Evaluation of a carp primary hepatocyte culture system for screening chemicals for oestrogenic activity. Aquat Toxicol, 94(3), 195-203.

The presence of endocrine disrupting chemicals (EDCs) in the environment has driven the development of screening and testing assays to both identify chemicals with hormonal activity and evaluate their potential to cause adverse effects. As the number of animals used for research and regulatory purposes rises, and set against a desire to reduce animal testing, there is increased emphasis on the development and application of in vitro techniques to evaluate chemical risks to the environment. Induction of vitellogenin (VTG) in isolated fish liver cells has been used successfully to identify a wide range of EDCs, including both natural and synthetic oestrogens and a variety of other xenoestrogens. However, the vitellogenic response reported for hepatocytes in culture has been shown to vary widely, making comparisons between studies difficult. The work presented in this paper explored the variability of the vitellogenic response in primary cultures of common carp (Cyprinus carpio) hepatocytes following exposure to the model oestrogenic compound, 17beta-oestradiol (E2). As expected, variability in the vitellogenic response was observed, both in terms of the sensitivity and magnitude of VTG induction, for hepatocytes isolated from different fish. An apparent difference was observed in the response of isolated hepatocytes based on the sex of the donor fish; maximum levels of E2-stimulated VTG synthesis in hepatocytes derived from females appeared higher (1962 ng mL(-1)+/-487 [n=9] compared with 1194 ng mL(-1)+/-223 for hepatocytes from males [n=9]) and EC(50) values lower (1.61+/-0.4 microM E2 for females and 2.12+/-0.2 microM E2 for males). However, these differences were not statistically significant, likely in part due to the variation observed in the vitellogenic response. In particular, hepatocytes derived from female fish showed more variation than their male counterparts (the co-efficient of variation for females was 77% compared to 28% for males). Despite the variation observed in the vitellogenic response between different cultures, data from the different donor fish could be compared by standardising responses relative to the maximum VTG induction in each culture following exposure to E2. Adopting this approach in the future will allow for data from different hepatocyte cultures and from donor fish of different sexes, age and stage of maturity to be compared with greater consistency. Measurement of vtg mRNA expression was relatively more sensitive to the oestrogenic effects of E2 exposure than measurement of VTG protein (the LOEC at the transcriptome level was 10-fold lower [0.01 microM E2] than at the protein level [0.1 microM E2]) and changes in vtg mRNA expression showed less variation between individual hepatocyte isolations. Measurement of vtg mRNA in the hepatocyte culture system therefore may offer the most sensitive and consistent option for the screening of chemicals with oestrogenic activity in fish primary hepatocyte cultures.

Abstract. Author URL.

Coe TS, Hamilton PB, Griffiths AM, Hodgson DJ, Wahab MA, Tyler CR (2009). Genetic variation in strains of zebrafish (Danio rerio) and the implications for ecotoxicology studies. Ecotoxicology, 18(1), 144-150. Abstract. Author URL.

Brown AR, Hosken DJ, Balloux F, Bickley LK, LePage G, Owen SF, Hetheridge MJ, Tyler CR (2009). Genetic variation, inbreeding and chemical exposure--combined effects in wildlife and critical considerations for ecotoxicology. Philos Trans R Soc Lond B Biol Sci, 364(1534), 3377-3390. Abstract. Author URL.

Paull GC, Filby AL, Tyler CR (2009). Growth rate during early life affects sexual differentiation in roach (Rutilus rutilus). Environmental Biology of Fishes, 85(4), 277-284. Abstract.

Williams TD, Wu H, Santos EM, Ball J, Katsiadaki I, Brown MM, Baker P, Ortega F, Falciani F, Craft JA, et al (2009). Hepatic transcriptomic and metabolomic responses in the stickleback (Gasterosteus aculeatus) exposed to environmentally relevant concentrations of dibenzanthracene. Environ Sci Technol, 43(16), 6341-6348. Abstract. Author URL.

Scown TM, van Aerle R, Johnston BD, Cumberland S, Lead JR, Owen R, Tyler CR (2009). High doses of intravenously administered titanium dioxide nanoparticles accumulate in the kidneys of rainbow trout but with no observable impairment of renal function. Toxicol Sci, 109(2), 372-380. Abstract. Author URL.

Coe TS, Hamilton PB, Hodgson D, Paull GC, Tyler CR (2009). Parentage outcomes in response to estrogen exposure are modified by social grouping in zebrafish. Environ Sci Technol, 43(21), 8400-8405. Abstract. Author URL.

Lange A, Paull GC, Coe TS, Katsu Y, Urushitani H, Iguchi T, Tyler CR (2009). Sexual reprogramming and estrogenic sensitization in wild fish exposed to ethinylestradiol. Environ Sci Technol, 43(4), 1219-1225. Abstract. Author URL. Full text.

Jobling S, Burn RW, Thorpe K, Williams R, Tyler C (2009). Statistical modeling suggests that antiandrogens in effluents from wastewater treatment works contribute to widespread sexual disruption in fish living in English rivers. Environ Health Perspect, 117(5), 797-802.

BACKGROUND: the widespread occurrence of feminized male fish downstream of some wastewater treatment works has led to substantial interest from ecologists and public health professionals. This concern stems from the view that the effects observed have a parallel in humans, and that both phenomena are caused by exposure to mixtures of contaminants that interfere with reproductive development. The evidence for a "wildlife-human connection" is, however, weak: Testicular dysgenesis syndrome, seen in human males, is most easily reproduced in rodent models by exposure to mixtures of antiandrogenic chemicals. In contrast, the accepted explanation for feminization of wild male fish is that it results mainly from exposure to steroidal estrogens originating primarily from human excretion. OBJECTIVES: We sought to further explore the hypothesis that endocrine disruption in fish is multicausal, resulting from exposure to mixtures of chemicals with both estrogenic and antiandrogenic properties. METHODS: We used hierarchical generalized linear and generalized additive statistical modeling to explore the associations between modeled concentrations and activities of estrogenic and antiandrogenic chemicals in 30 U.K. rivers and feminized responses seen in wild fish living in these rivers. RESULTS: in addition to the estrogenic substances, antiandrogenic activity was prevalent in almost all treated sewage effluents tested. Further, the results of the modeling demonstrated that feminizing effects in wild fish could be best modeled as a function of their predicted exposure to both antiandrogens and estrogens or to antiandrogens alone. CONCLUSION: the results provide a strong argument for a multicausal etiology of widespread feminization of wild fish in U.K. rivers involving contributions from both steroidal estrogens and xenoestrogens and from other (as yet unknown) contaminants with antiandrogenic properties. These results may add further credence to the hypothesis that endocrine-disrupting effects seen in wild fish and in humans are caused by similar combinations of endocrine-disrupting chemical cocktails.

Abstract. Author URL.

Sebire M, Scott AP, Tyler CR, Cresswell J, Hodgson DJ, Morris S, Sanders MB, Stebbing PD, Katsiadaki I (2009). The organophosphorous pesticide, fenitrothion, acts as an anti-androgen and alters reproductive behavior of the male three-spined stickleback, Gasterosteus aculeatus. Ecotoxicology, 18(1), 122-133. Abstract. Author URL.

Thorpe KL, Benstead R, Eccles P, Maack G, Williams T, Tyler CR (2008). A practicable laboratory flow-through exposure system for assessing the health effects of effluents in fish. Aquat Toxicol, 88(3), 164-172. Abstract. Author URL.

Lange A, Katsu Y, Ichikawa R, Paull GC, Chidgey LL, Coe TS, Iguchi T, Tyler CR (2008). Altered sexual development in roach (Rutilus rutilus) exposed to environmental concentrations of the pharmaceutical 17alpha-ethinylestradiol and associated expression dynamics of aromatases and estrogen receptors. Toxicol Sci, 106(1), 113-123. Abstract. Author URL.

Coe TS, Hamilton PB, Hodgson D, Paull GC, Stevens JR, Sumner K, Tyler CR (2008). An environmental estrogen alters reproductive hierarchies, disrupting sexual selection in group-spawning fish. Environ Sci Technol, 42(13), 5020-5025. Abstract. Author URL.

Williams TD, Brown M, Chipman JK, Falciani F, Ortega F, Geoghegan F, Craft JA, Katsiadaki I, Ball J, Tyler CR, et al (2008). Development of a stickleback (Gasterosteus aculeatus) cDNA microarray and gene expression responses to dibenzanthracene, ethinyl-estradiol and copper. MARINE ENVIRONMENTAL RESEARCH, 66(1), 140-140. Author URL.

Benstead, R. Eccles, P. Maack, G. (2008). Effective assessment of the oestrogenic activity of effluents using a laboratory flow-through exposure system. Aquatic Toxicology

van Aerle R, Kille P, Lange A, Tyler CR (2008). Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish. Peptides, 29(1), 57-64. Abstract. Author URL.

Johnston, B.J. Tyler, C.R. (2008). Imaging metal oxide nanoparticles in biological structures with CARS microscopy. Optical Express, 16(5), 3408-3419.

Handy RD, Henry TB, Scown TM, Johnston BD, Tyler CR (2008). Manufactured nanoparticles: their uptake and effects on fish--a mechanistic analysis. Ecotoxicology, 17(5), 396-409.

There is an emerging literature reporting toxic effects of manufactured nanomaterials (NMs) and nanoparticles (NPs) in fish, but the mechanistic basis of both exposure and effect are poorly understood. This paper critically evaluates some of the founding assumptions in fish toxicology, and likely mechanisms of absorption, distribution, metabolism and excretion (ADME) of NPs in fish compared to other chemicals. Then, using a case study approach, the paper compares these assumptions for two different NPs; TiO2 and C60 fullerenes. Adsorption of NPs onto the gill surface will involve similar processes in the gill microenvironment and mucus layer to other substances, but the uptake mechanisms for NPs by epithelial cells are more likely to occur via vesicular processes (e.g. endocytosis) than uptake on membrane transporters or by diffusion through the cell membranes. Target organs may include the gills, gut, liver and sometimes the brain. Information on metabolism and excretion of NPs in fish is limited; but hepatic excretion into the bile seems a more likely mechanism, rather than mainly by renal or branchial excretion. TiO2 and C60 share some common chemical properties that appear to be associated with some similar toxic effects, but there are also differences, that highlight the notion that chemical reactivity can inform toxic effect of NPs in a fundamentally similar way to other chemicals. In this paper we identify many knowledge gaps including the lack of field observations on fish and other wildlife species for exposure and effects of manufactured NMs. Systematic studies of the abiotic factors that influence bioavailability, and investigation of the cell biology that informs on the mechanisms of metabolism and excretion of NMs, will greatly advance our understanding of the potential for adverse effects. There are also opportunities to apply existing tools and techniques to fundamental studies of fish toxicology with NPs, such as perfused organs and fish cell culture systems.

Abstract. Author URL.

Ibañez, A. Tyler, C.R. Prat, F. (2008). Molecular characterisation of growth differentiation factor 9 (gdf9) and bone morphogenetic protein 15 (bmp15) and their patterns of gene expression during the ovarian reproductive cycle in the European sea. bass. Molecular and Cellular Endocrinology

Paull GC, Lange A, Henshaw AC, Tyler CR (2008). Ontogeny of sexual development in the roach (Rutilus rutilus) and its interrelationships with growth and age. J Morphol, 269(7), 884-895. Abstract. Author URL.

Tyler CR, Jobling S (2008). Roach, sex, and gender-bending chemicals: the feminization of wild fish in English rivers. BioScience, 58(11), 1051-1059. Abstract.

Kille, P. Workman, V.L. Paull, G.C. (2008). Sexually dimorphic gene expression in the brains of mature zebrafish. Comparative Biochemistry and Physiology Part A

Paull, G.C. van Look, K.J.W. Santos, E.M. Filby A.L. Gray D.M. Nash, J.P. & Tyler, C.R (2008). Variability in measures of reproductive success in laboratory-kept colonies of zebrafish (Danio rerio) and implications for studies addressing population-level effects of environmental chemicals. Aquatic Toxicology

Tyler, C.R. (2007). Cloning and Characterisation of cDNAs for hormones and/or receptors of growth hormone, insulin-like growth factor-I, thyroid hormone, and corticosteroid and the gender- and tissue- and developmental-specific expression of their mRNA transcripts in fathea. General & Comparative Endocrinology, 150, 151-163.

Katsu, Y. Urushitani, H. Lange, A. (2007). Developmental effects of exposure to. pharmaceutical steroids in the aquatic environment: Studies in Mosquitofish (Gambusia affinis), Roach. (Rutilus rutilus) and Medaka (Oryzias latipes. Journal of Marine Science and Technology

Hetheridge, M. Hutchinson, T.H. Benstead, R. (2007). An optimized experimental test procedure for measuring chemical effects on reproduction in the fathead minnow (Pimephales promelas). Aquatic Toxicology, 8(1), 90-98.

Filby AL, Tyler CR (2007). Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish. BMC Mol Biol, 8 Abstract. Author URL.

Benstead, R. Hutchinson, T.H. Tyler, C.R. (2007). Associations between altered vitellogenin concentrations and adverse health effects in fathead minnow (Pimephales promelas. Aquatic Toxicology

Trudeau V, Tyler C (2007). Endocrine disruption. Gen Comp Endocrinol, 153(1-3), 13-14. Author URL.

Schulz RW, Bogerd J, Male R, Ball J, Fenske M, Olsen LC, Tyler CR (2007). Estrogen-induced alterations in amh and dmrt1 expression signal for disruption in male sexual development in the zebrafish. Environmental Science and Technology, 41(17), 6305-6310. Abstract.

Bickley L, Lange A, Tyler C, Winter M (2007). Fish hepatocyte cultures as an alternative to in vivo tests for screening oestrogen receptor active chemicals. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 146(4), S72-S72. Author URL.

Jobling, S. (2007). Fish, Sex and Gender-Bending Chemicals – the Feminization of Fish Living in English Rivers. Biosciences

Lange, A. Ichikawa, R. Urushitani, H.G.C. (2007). Functional associations between two estrogen receptors, environmental oestrogens, and sexual disruption in the roach (Rutilus rutilus). Environmental Science and Technology, 41(9), 3368-3374.

Thorpe, K.L. Maack, G. Tyler, C.R. (2007). Gene expression profiles revealing the mechanisms of anti-androgen- and oestrogen- induced feminisation in fish. Aquatic Toxicology, 81(2), 219-231.

Santos, E.M. Thorpe, K.L. Maack, G. (2007). Gene expression profiling for understanding chemical causation of biological effects of complex mixtures: a Case Study for Estrogens. Environmental Science and Technology

Santos, E.M. Paull, G.C. Van Look, K.J.W. Workman, V.L. Holt, W.V. van Aerle, R. Kille, P. & Tyler, C.R (2007). Gonadal transcriptome responses and physiological consequences of exposure to oestrogen in breeding zebrafish (Danio rerio). Aquatic Toxicology, 83(2), 134-142.

Tyler CR, Filby AL, Galloway TS, Neuparthe T (2007). Health impacts of estrogens in the environment, considering complex mixture effects. Full text.

Tyler, C.R. (2007). Identification of microsatellite loci for parentage analysis in roach Rutilus rutilus and 8 other cyprinids by cross-species amplification, and a novel test for detecting hybrids between roach and other cyprinids. Molecular Ecology Notes

Workman, V.L. Paull, G.C. Filby, A.L. (2007). Molecular basis of sex and reproductive status in breeding zebrafish. Physiological Genomics, 30(2), 111-122.

Boegard, J. Male, R. Ball, J. (2007). Oestrogen-induced alterations in the expression of AMH and DMRT-1 during sexual differentiation signal for impacts on male sexual development in the zebrafish (Danio rerio). Environmental Science and Technology, 41(17), 6305-6310.

Tyler C, Lange A, Santos E, Filby A (2007). The application of transcriptomics and other molecular approaches in advancing our understanding of endocrine disruption. TOXICOLOGY LETTERS, 172, S27-S27. Author URL.

Katsu, Y. Kato, Y. Tooi, O. (2007). The medaka (Oryyzias latipes) for assessing developmental effects of endocrine disrupting chemicals with special reference to gonadal intersex (testis-ova. Environmental Science

Tyler CR, Lange A, Paull GC, Katsu Y, Iguchi T (2007). The roach (Rutilus rutilus) as a sentinel for assessing endocrine disruption. Environ Sci, 14(5), 235-253. Abstract. Author URL.

Hutchinson, T.H. Hurd, K.S. Bamforth, J. (2006). Development of chronic tests for endocrine active chemicals. Part I. An extended fish early- life stage test for oestrogen active chemicals in the fathead minnow Pimephales promelas. Aquatic Toxicology, 77, 279-290.

Kennedy, S. Snape, J. Tillet, D. (2006). An Evaluation of the Potential Role of Genomics in Regulatory Ecotoxicology. Environmental Science and Technology, 40(13), 4055-4065.

Gross-Sorokin, M. Johnson, I. Brighty, G. (2006). An assessment of the model of concentration addition for predicting the estrogenic activity of chemical mixtures in wastewater treatment works effluent. Environmental Health Perspectives, 114, 90-97.

Schulte-Oehlmann, U, Albanis T, Allera A, Bachmann J, Berntsson P, Beresford N, Carnevali DC, Ciceri F, Dagnac T, Falandysz J, et al (2006). COMPRENDO: Focus and approach. Environmental Health Perspectives, 114(1), 98-100.

Eidem JK, Kleivdal H, Kroll K, Denslow N, van Aerle R, Tyler C, Panter G, Hutchinson T, Goksoyr A (2006). Development and validation of a direct homologous quantitative sandwich ELISA for fathead minnow (Pimephales promelas) vitellogenin. Aquatic Toxicology, 78(2), 202-206.

Santos E, Paull G, Filby A, Tyler C, Van Look K, Holt W, Workman V, Kille P (2006). Gender and stage-specific transcriptomic profiles of gonads and brains in breeding zebrafish. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 143(4), S101-S101. Author URL.

tsgallo1, Hagger JA, Liney KE, Tyler CR (2006). Health effects in fish of long-term exposure to effluents from wastewater treatment works. Environmental Health Perspectives, 114(S1), 81-89. Full text.

Jobling S, Tyler CR (2006). Introduction: the ecological relevance of chemically induced endocrine disruption in wildlife. ENVIRONMENTAL HEALTH PERSPECTIVES, 114, 7-8. Author URL.

Thorpe, K.L. Tyler, C.R. (2006). Multiple molecular effect pathways for an environmental. oestrogen in fish. Journal of Endocrinology, 37, 121-134.

Ankley, G.T. Segner, H. Tyler, C.R. (2006). Screening and testing for endocrine. disruption in fish -. biomarkers as signposts not traffic lights in risk assessment. Environmental Health Perspectives, 114, 106-114.

Filby A, Thorpe K, Tyler C (2006). The developmental expression of three oestrogen receptor subtypes and their differential responses to oestrogen in fish. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 143(4), S101-S101. Author URL.

Tyler, C.R. (2006). The ecological relevance of chemically-induced endocrine disruption in wildlife. Environmental Health Perspectives, 114, 7-8.

Ankley GT, Daston GP, Degitz SJ, Denslow ND, Hoke RA, Kennedy SW, Miracle AL, Perkins EJ, Snape J, Tillitt DE, et al (2006). Toxicogenomics in regulatory ecotoxicology. Environmental Science and Technology, 40(13), 4055-4065. Abstract.

Tyler CR, Spary C, Gibson R, Santos EM, Shears J, Hill EM (2005). Accounting for differences in estrogenic responses in rainbow trout (Oncorhynchus mykiss: Salmonidae) and roach (Rutilus rutilus: Cyprinidae) exposed to effluents from wastewater treatment works. Environ Sci Technol, 39(8), 2599-2607.

Effluents from wastewater treatment works (WwTWs) contain estrogenic substances that induce feminizing effects in fish, including vitellogenin (VTG) synthesis and gonadal intersex. Fish vary in their responsiveness to estrogenic effluents, but the physiological basis for these differences are not known. In this study, uptake of estrogen from two WwTW effluents (measured in hydrolyzed bile) and estrogenic response (VTG induction) were compared in a salmonid (rainbow trout, Onchorhynchus mykiss) and a cyprinid fish (roach, Rutilus rutilus). Immature rainbow trout were more responsive than maturing roach to the estrogenic effluents. The more potent of the two estrogenic effluents (containing between 24.3 and 104.1 ng estradiol-17beta equivalents/L [E2eq/L]) resulted in a 700-fold and 240-fold induction of plasma VTG in male and female trout, respectively, but only a 4-fold induction in roach (and in males only). The less potent effluent (varying between 4.1 and 6.8 ng E2eq/L) induced VTG in the trout only, with a 4-fold and 18-fold induction in males and females, respectively. In fish exposed to tap water, the estrogenicity of the hydrolyzed bile was 0.03+/-0.01 ng E2eq/microL (for both sexes in trout), 0.18+/-0.04 ng E2eq/microL in male roach, and 0.88+/-0.15 ng E2eq/microL in female roach. The higher bile content of estrogen in control roach reflected their more advanced sexual status (and thus higher endogenous estrogen) compared with the immature female trout. In trout maintained in effluents, the bile content of estrogen was 100-fold and 30-fold higher than controls at WwTW a and B, respectively. Bioconcentration factors (BCFs) for estrogenic activity in bile were between 16 344 and 46 134 in trout and between 3543 and 60 192 in roach (no gender differences were apparent). There were strong correlations between VTG induction and the estrogenic activity of bile extracts for both trout and roach. The results confirm that estrogenic contaminants bioconcentrate to a high degree in fish bile and that the level (and nature) of this accumulation may accountfor responsiveness to the endocrine disruptive effects of estrogenic effluents. Immature fish were the more appropriate life stage for quantifying estrogen exposure and uptake in bile, as they contain little circulating endogenous oestrogen compared with sexual maturing fish. The nature of the estrogenic contaminants is detailed in an accompanying paper.

Abstract. Author URL.

Tyler, C.R. Hill, E.M. (2005). An analytical methodology for the identification of estrogenic contaminants in fish bile. Journal of Chromatography A, 1066, 33-40.

Jobling, S. Shears, J. Simpson, P. (2005). Assessing the sensitivity of different life stages. for sexual disruption in roach (Rutilus rutilus) exposed to effluents from wastewater treatment works. Environmental Health Perspectives, 113(10), 1299-1307.

Fenske, M. Verslycke, T. Tyler, C.R. (2005). Development of a quantitative enzyme- linked immunosorbent assay for vitellin and its application in a preliminary study on vitellogenesis in the mysid, Neomysis intege. Comparative Biochemistry and Physiology Part B

Ghekiere A, Fenske M, Verslycke T, Tyler C, Janssen C (2005). Development of a quantitative enzyme-linked immunosorbent assay for vitellin in the mysid Neomysis integer (Crustacea: Mysidacea). Comp Biochem Physiol a Mol Integr Physiol, 142(1), 43-49. Abstract. Author URL.

Shears, J. van Aerle, R. (2005). Endocrine (sexual) disruption is not a prominent feature in the pike (Esox lucius), a top predator, living in English waters. Environmental Toxicology and Chemistry, 24(6), 1436-1443.

Smith, M.D. Spary, C. Tyler, C.R. (2005). Mixtures of oestrogenic contaminants in bile in fish exposed to wastewater treatment works effluents. Environmental Science and Technology, 39(8), 2461-2471.

Tyler, C.R. (2005). Molecular characterization of estrogen receptors 1, 2a and 2b and their tissue and ontogenic expression profiles in fathead minnow (Pimephales promelas). Biology of Reproduction, 73, 648-662.

Williams, R. Johnson, A. (2005). Predicted exposures to steroid estrogens in UK Rivers correlate with widespread sexual disruption in wild fish populations. Environmental Health Perspectives, 32-39.

Sauer, A. Shears, J. Tyler, C.R. (2004). Androgenic and oestrogenic effects of the synthetic androgen, 17-methyltestosterone on sexual development and reproductive performance in the fathead minnow (Pimephales promelas) determined using a gonadal recrudescence assay. Aquatic Toxicology, 68(3), 277-291.

Jobling S, Casey D, Rodgers-Gray T, Oehlmann J, Schulte-Oehlmann U, Pawlowski S, Baunbeck T, Turner AP, Tyler CR (2004). Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent (vol 65, pg 205, 2003). AQUATIC TOXICOLOGY, 66(2), 205-+. Author URL.

Jobling S, Casey D, Rogers-Gray T, Oehlmann J, Schulte-Oehlmann U, Pawlowski S, Baunbeck T, Turner AP, Tyler CR (2004). Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent. Aquat Toxicol, 66(2), 207-222.

It is now well established that there is a diverse array of chemical discharged into the environment that can mimic or antagonise the action of hormones. These endocrine-disrupting chemicals (EDCs) can thus interact with physiological systems and cause alterations in development, growth and reproduction in wildlife that are exposed to them. As yet, however, there is little information on the relative sensitivities of different wild life groups to these chemicals and/or mixtures of them (e.g. estrogenic effluents) and hence, there are fundamental shortfalls in our knowledge of the ecological chemicals (17alpha-ethinylestradiol; EE2, bisphenol-A, and 4-tert octylphenol) and a mixture containing these chemicals (treated sewage effluent) on embryo production in the prosobranch mollusc, Potamopyrgus antipodarum, were studied and compared with the effects of EE2 and the same estrogenic effluent on vitellogenin induction and/or egg production in various species of freshwater fish (fathead minnow; Pimaphales promelas, rainbow trout (Oncorhynchus mykiss); Cyprinus carpio, carp; Cyprinus carpio). The lab-based studies demonstrated that all of the tested chemicals (known to be estrogenic and to cause reproductive effects in fish) also affected embryo production in P. antipodarum. Furthermore, exposure to EE2 induced similar reproductive responses in the snails as in the fathead minnow (Pimephales promelas), stimulating egg/embryo production at low doses (up to 1 ng/l in the minnow and 25 ng/l in the snail) and causing inhibitory effects at higher doses. A similar pattern of embryo production occurred in P. antipodarum when it was exposed to a graded concentration of treated sewage effluent containing mixtures of estrogenic EDCs and hence, the total number of new embryos produced by the snails increased steadily over the 9 week exposure period in treated snails. Plasma vitellogenin concentrations in two species of male fish (the rainbow trout and the carp) also increased over the same time period. These data indicate that both the nature of the response and the relative sensitivities to environmental estrogens in P. antipodarum and three different fish species fish are comparable. P. andtipodarum is thus, potentially a sensitive test organism for assessing estrogenicity of chemicals with a relevance to their activity in vertebrates.

Abstract. Author URL.

Tyler CR, van Aerle R, Santos EM (2004). ELISAs for detecting vitellogenin in the fathead minnow (Pimephales promelas)-a critical analysis. Response to Mylchreest et al. Comp Biochem Physiol C 134: 251-257, 2003. Comp Biochem Physiol C Toxicol Pharmacol, 138(4), 531-532. Author URL.

van Aerle, R. Tyler, C.R. (2004). Effects of 17 alpha-ethinylestradiol in a fathead minnow (Pimephales promelas) gonadal recrudescence assay. Ecotoxicology and Environmental Safety, 57(3), 330-345.

Spano, L. Tyler, C.R. van Aerle R, Devos, P. Mandiki SNM, Silvestre F, Thome JP, Kestemont P (2004). Effects of atrazine on sex steroid dynamics, plasma vitellogenin concentration and gonad development in adult goldfish (Carassius auratus). Aquatic Toxicology, 66(4), 369-379.

Jobling S, Casey C, Rodgers-Gray T, Oehlmannd J, Schulte-Oehlmann U, Pawlowski S, Baunbeck T, Turner AP, Tyler CR (2004). Erratum: Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent (Aquatic Toxicology (2003) 65 (205-220)). Aquatic Toxicology, 66(2), 205-222.

Tyler, C.R. Palazzi, X. Laillet, B. (2004). Impacts of. 17- estradiol, including environmentally relevant concentrations, on reproduction after exposure during embryo-larval-juvenile and adult-life stages in zebrafish (Danio rerio). Aquatic Toxicology, 68(3), 193-217.

Nash, J.P. Kime, D.E. Van der Ven, L.T.M. (2004). Long-term exposure to environmental concentrations of the pharmaceutical ethinyloestradiol cause \r reproductive failure in fish. Environmental Health Perspectives, 112(17), 1725-1733. Full text.

van Aerle, R. Runnalls, T. & Tyler, C.R (2004). Ontogeny of gonadal sex development relative to growth in. fathead minnow (Pimephales promelas). Journal of Fish Biology, 64, 355-369.

van Aerle, R, Runnalls, T.J. Tyler, C.R. (2004). Ontogeny of gonadal sex development relative to growth in fathead minnow. Journal of Fish Biology, 64(2), 355-369.

Benstead, R. Hutchinson, T.H. Cummings, R.I. (2004). Reproductive effects of. exposure to oestrone in the fathead minnow. Fish Physiology and Biochemistry, 28, 451-452.

Hutchinson, T.H. Hurd, K.S. Sherren, A. (2004). Successful detection of (anti-) androgenic and aromatase inhibitors in pre-spawning fathead minnows (Pimephales promelas) using easily measured endpoints of sexual development. Aquatic Toxicology, 70, 11-21.

Kwon, J. Rand-Weaver, M. Sumpter, J.P. (2003). Cloning and gene expression of 17,20- lyase cDNA in the gonads and brain of the fathead minnow (Pimephales promelas). General & Comparative Endocrinology, 130, 256-266.

Casey, D. Rodgers-Gray, T. Oehlmann, J. (2003). Comparative responses of molluscs and fish to environmental oestrogens and an oestrogenic effluent. Aquatic Toxicology, 65, 205-220.

Thomas-Jones E, Thorpe K, Harrison N, Thomas G, Morris C, Hutchinson T, Woodhead S, Tyler C (2003). Dynamics of estrogen biomarker responses in rainbow trout exposed to 17beta-estradiol and 17alpha-ethinylestradiol. Environ Toxicol Chem, 22(12), 3001-3008. Abstract. Author URL.

Tyler, C.R. (2003). Endocrine Disruption in Wild Freshwater Fish. Pure and Applied Chemistry, 75(11-12), 2219-2234.

Tyler, C.R. (2003). Impacts of Endocrine Disruption, Parasites and Pollution in Freshwater Fish. Journal of Parasitology, 126, 103-108.

Segner, H. Tyler, C.R. (2003). Ontogeny of sexual differentiation in different strains of zebrafish (Danio rerio). Fish Physiology and Biochemistry, 28, 125-128.

Tyler CR, Hetheridge MJ, Scholze M, Thorpe K (2003). Relative potencies and combination effects of steroidal oestrogens in fish. Environmental Science & Technology, 37(6), 1142-1149.

Pickford, K.A. Wheale, B.Thomas,-Jones, E. Tyler, C.R. & Sumpter, J.P (2003). Route of exposure affects the oestrogenic responses of fish to 4-tert nonylphenol. Aquatic Toxicology, 65, 267-279.

Tyler CR, Beresford N, Jobling S, Nolan M (2002). Altered sexual maturation and gamete production in wild roach (Rutilus rutilus) living in rivers that receive treated sewage effluents. Biology of Reproduction, 66(2), 272-281.

Lye, C. Tyler, C.R. Sumpter, J.P. (2002). Effects of treatment processes on the endocrine activity of various influents as they pass through waster water treatment works\r. Environmental Toxicology and Chemistry, 21(5), 972-979.

Rand-Weaver, M. Sumpter, J.P. Tyler, C.R. (2002). Exposure to exogenous oestradiol 17 disrupts P450 aromatase B mRNA expression in the brain and ovary of adult fathead minnow (Pimephales promelas).\r. Aquatic Toxicology, 60, 285-299.

Tyler CR, van Aerle R, Nilsen MV, Blackwell R, Maddix S, Nilsen BM, Berg K, Hutchinson TH, Goksøyr A (2002). Monoclonal antibody enzyme-linked immunosorbent assay to quantify vitellogenin for studies on environmental estrogens in the rainbow trout (Oncorhynchus mykiss). Environ Toxicol Chem, 21(1), 47-54. Abstract. Author URL.

Tyler, C.R. Maddix, S. Karbe, L. (2002). Plasma biomarkers in fish provide evidence for endocrine modulation in the Elbe River, Germany. Environmental Science and Technology, 36(11), 2311-2321.

Campbell, P.M. Hutchinson, T.H. Kime, D.E. (2002). Utility of. a fathead. minnow juvenile fish screening assay for detecting. (anti-) oestrogenic substances. Environmental Toxicology and Chemistry, 21, 319-326.

Jobling S, Coey S, Whitmore JG, Kime DE, Van Look KJW, McAllister BG, Beresford N, Henshaw AC, Brighty G, Tyler CR, et al (2002). Wild intersex roach (Rutilus rutilus) have reduced fertility. Biol Reprod, 67(2), 515-524.

Endocrine-disrupting chemicals, known to be present in the environment, have great potential for interfering with reproductive health in wildlife and humans. There is, however, little direct evidence that endocrine disruption has adversely affected fertility in any organism. In freshwater and estuarine fish species, for example, although a widespread incidence of intersex has been reported, it is not yet known if intersexuality influences reproductive success. The purpose of this study was, therefore, to determine gamete quality in wild intersex roach (Rutilus rutilus) by assessing sperm characteristics, fertilization success, and ability to produce viable offspring. The results clearly demonstrate that gamete production is reduced in intersex roach. A significantly lower proportion of moderately or severely feminized fish (17.4% and 33.3%, respectively) were able to release milt compared with normal male fish from contaminated rivers (in which 97.6% of the males were able to release milt), reference male fish (97.7%), or less severely feminized intersex fish (experiment 1: 85.8%, experiment 2: 97%). Intersex fish that did produce milt produced up to 50% less (in terms of volume per gram of testis weight) than did histologically normal male fish. Moreover, sperm motility (percentage of motile sperm and curvilinear velocity) and the ability of sperm to successfully fertilize eggs and produce viable offspring were all reduced in intersex fish compared with normal male fish. Male gamete quality (assessed using sperm motility, sperm density, and fertilization success) was negatively correlated with the degree of feminization in intersex fish (r = -0.603; P < 0.001) and was markedly reduced in severely feminized intersex fish by as much as 50% in terms of motility and 75% in terms of fertilization success when compared with either less severely feminized intersex fish or unaffected male fish. This is the first evidence documenting a relationship between the morphological effects (e.g. intersex) of endocrine disruption and the reproductive capabilities of any wild vertebrate. The results suggest that mixtures of endocrine-disrupting substances discharged into the aquatic environment could pose a threat to male reproductive health.

Abstract. Author URL.

van Aerle R, Pounds N, Hutchinson TH, Maddix S, Tyler CR (2002). Window of sensitivity for the estrogenic effects of ethinylestradiol in early life-stages of fathead minnow, Pimephales promelas. Ecotoxicology, 11(6), 423-434. Abstract. Author URL.

Jobling, S. Sumpter, J.P. Brighty, G. (2001). A histological. description of intersexuality in the roach. Journal of Fish Biology, 58, 160-176.

Tyler CR, Hetheridge M, Scholze M, Thorpe K (2001). Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss) . Environmental Science & Technology, 35(12), 2476-2481.

Rand-Weaver, M. Sumpter, J.P. Tyler, C.R. (2001). Cloning and molecular characterisation of an ovarian-derived (brain-like) P450-aromatase. and development. of a. competitive rtPCR bioassay to quantify its expression in the fathead minnow (Pimephales promelas ). Fish Physiology and Biochemistry, 24, 49-62.

van Aerle, R. Brack, S. (2001). Development and validation of a homologous zebrafish (Danio rerio Hamilton-Buchanan) vitellogenin enzyme-linked immunosorbent assay (ELISA) and its application for studies on estrogenic chemicals. Comparative Biochemistry and Physiology C-Toxicology & Pharmacology, 129(3), 217-232.

Rand-Weaver, M. Tyler, C.R. (2001). Development and validation of radioimmunoassays for follicle stimulating hormone and its alpha and beta sub-units and their seasonal plasma and pituitary concentrations in the rainbow trout (Oncorhynchus mykiss). Biology of Reproduction, 65, 288-294.

van Aerle, R. Jobling, S. Christiansen. L. Sumpter, J.P and Tyler, C.R. (2001). Evidence for sexual disruption in a second species of freshwater fish (gudgeon, Gobio gobio) living in UK rivers receiving sewage treatment works effluent. Environmental Toxicology and Chemistry, 20, 2841-2847.

Jobling, S. Kelly, C. (2001). Exposure of juvenile roach, Rutilus rutilus, to treated sewage effluent induces dose-dependent and persistent disruption in gonadal development. Environmental Science and Technology, 35(3), 462-470.

Santos, E. Pottinger, T.G. Tyler, C.R. (2001). Exposure to 4 tert –nonylphenol alters gonadotrophin dynamics. in the pituitary and. plasma of. female rainbow trout (Oncorhynchus mykiss ). Environmental Science and Technology, 35, 2909-2916.

Santos EM, Rand-Weaver M, Tyler CR (2001). Follicle-stimulating hormone and its alpha and beta subunits in rainbow trout (Oncorhynchus mykiss): purification, characterization, development of specific radioimmunoassays, and their seasonal plasma and pituitary concentrations in females. Biol Reprod, 65(1), 288-294. Abstract. Author URL.

Cavaco, J.E.B. Rebers, F.E.M. Vischer, H.F. (2001). Gonadotrophins, their receptors, and regulation of testicular functions in fish. Comparative Biochemistry and Physiology Part B, 129, 407-417.

Prat, F. Randall, C. Tyler, C.R. (2001). Molecular characterisation of putative yolk processing enzymes and their expression during oogenesis and embryo development in the rainbow trout, Oncorhynchus mykiss. Biology of Reproduction, 65, 1701-1709.

Harris CA, Santos EM, Janbakhsh A, Pottinger TG, Tyler CR, Sumpter JP (2001). Nonylphenol affects gonadotropin levels in the pituitary gland and plasma of female rainbow trout. Environ Sci Technol, 35(14), 2909-2916. Abstract. Author URL.

Tyler, C.R. Toy, R. Caunter, J. (2001). Reproductive effects of long term exposure to Bisphenol a in the fathead minnow (Pimephales promelas ). Environmental Science and Technology, 35, 2917-2925.

Van Aerle R, Christiansen LB, Jobling S, Tyler CR (2001). Sexual disruption in a second species of wild cyprinid fish (the Gudgeon, Gobio gobio) in United Kingdom freshwaters. Environmental Toxicology and Chemistry, 20(12), 2841-2847.

Runnalls, T. Harris, C. Hill, E. (2000). Development of a reproduction performance test for endocrine-disrupting chemicals in the fathead minnow (Pimephales promelas. Environmental Science and Technology, 34, 3003-3011.

Hutchinson, T.H. Hetheridge, M. Sumpter, J.P. (2000). Development of an in vivo. screening assay for estrogenic chemicals using juvenile rainbow trout, Oncorhynchus mykiss. Environmental Toxicology and Chemistry, 19, 2812-2820.

Brion, F. Palazzi, X. Babut, M. (2000). Estrogenic effects in chub (Leuciscus cephalus): Induction of vitellogenin and alterations in testicular structure. Ecotoxicology, 9, 127-135.

Jobling, S. Morris, S. Kelly, C. (2000). Long-term temporal changes in the oestrogenic composition of treated sewage effluent and its biological effects in fish. Environmental Science and Technology, 34, 1521-1528.

Tyler, C.R. Beresford, N. van der Woning, M. Sumpter, J.P. & Thorpe, K (2000). Metabolism and. environmental degradation of pyrethroid. insecticides produce compounds with endocrine activities. Environmental Toxicology and Chemistry, 19, 801-809.

May, D. Rand-Weaver, M. Tyler, C.R. (2000). Molecular characterisation of the first non-mammalian p73 cDNA. Comparative Biochemistry and Physiology Part B, 126, 49-57.

Tyler, C.R. van Aerle, R. Hutchinson, T. Maddix, S, & Trip, H (1999). An in vivo. testing system for endocrine disrupters in fish early life stages using induction of vitellogenin. Environmental Toxicology and Chemistry, 18(2), 337-347.

Perazzolo, L. Coward, K. Davail, B. Normand, E. Tyler, C.R. Pakdel, F. Schneider, W. & Le Menn, F (1999). Expression and localisation of messenger ribonucleic acid for the vitellogenin receptor in ovarian follicles throughout oogenesis in the rainbow trout, Oncorhynchus mykiss. Biology of Reproduction, 60, 1057-1068.

May, D. Rand-Weaver, M. Tyler, C.R. (1999). Fish p53 - a possible biomarker for genotoxins in the aquatic environment?. Environmental and Molecular Mutagenesis, 33, 144-151.

Bhaskaran A, May D, Rand-Weaver M, Tyler CR (1999). Fish p53 as a possible biomarker for genotoxins in the aquatic environment. Environ Mol Mutagen, 33(3), 177-184. Abstract. Author URL.

Jambakhsh, A. Jobling, S. Matthiessen, P. (1999). Oestrogenic potency of effluent from two sewage-treatment works in the United Kingdom. Environmental Toxicology and Chemistry, 18, 932-937.

Jobling, S. Sumpter, J.P. (1998). Endocrine disruption in wildlife: a critical review of the. evidence\r. Critical Reviews in Toxicology, 28(4), 319-361.

Coward, K. Sumpter, J.P. Tyler, C.R. (1998). Molecular characterisation and expression of two ovarian lipoprotein receptors in the rainbow trout, Oncorhynchus mykiss. Biology of Reproduction, 58, 1146-1153.

Routledge, E. (1998). Oestrogenic effects in fish in English rivers with evidence for causation. Pure and Applied Chemistry, 70, 1795-1804.

Nolan, M. Tyler, C.R. Brighty, G. (1998). Widespread sexual disruption in wild fish. Environmental Science and Technology, 32, 2498-2506.

Tyler, C.R. Sumpter, J.P. (1997). Egg quality in fish; what makes a good egg? \r. Reviews in Fish Biology and Fisheries, 7, 387-416.

Tyler, C.R. Carnevali, O. Coward, K. (1997). Molecular characterisation of ovarian cathepsin D in the rainbow trout, Oncorhynchus mykiss. Gene, 201, 45-54.

Brooks S, Tyler CR, Sumpter JP (1997). Quality in fish: what makes a good egg?. REVIEWS IN FISH BIOLOGY AND FISHERIES, 7(4), 387-416. Author URL.

Pottinger, T.G. Coward, K. Prat, F. (1997). Salmonid follicle stimulating hormone (GtH I) mediates. vitellogenic development of oocytes in the rainbow trout, Oncorhynchus mykiss. Biology of Reproduction, 57, 1238-1244.

Nagler JJ, Scott AP, Tyler CR, Sumpter JP (1996). Gonadotropins I and II do not stimulate the in vitro secretion of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate by rainbow trout gonads during final sexual maturation. FISH PHYSIOLOGY AND BIOCHEMISTRY, 15(2), 149-156. Author URL.

Lubberink, K. (1996). Identification of four ovarian receptor proteins that bind vitellogenin, but not other homologous plasma lipoproteins, in the rainbow trout, Oncorhynchus mykiss. Journal of Comp. Physiol.B, 166, 11-20.

Tyler, C.R. van der Eerden, Sumpter, J.P. Jobling, S. & Panter, G (1996). Measurement of vitellogenin, a biomarker for exposure to oestrogen, in a wide variety of cyprinids. Journal of Comp. Physiol.B, 166, 418-426.

Tyler CR, Pottinger TG, Santos E, Sumpter JP, Price SA, Brooks S, Nagler JJ (1996). Mechanisms controlling egg size and number in the rainbow trout, Oncorhynchus mykiss. Biol Reprod, 54(1), 8-15. Abstract. Author URL.

Sumpter, J.P. (1996). Oocyte growth and development in teleosts. Reviews in Fish Biology and Fisheries, 6, 287-318.

Sumpter, J.P. Tyler, C.R. (1996). Validation of radioimmunoassays for two salmon gonadotropins (gonadotropins I and II) and their plasma concentrations throughout the reproductive cycle in male and female rainbow trout, Oncorhynchus mykiss. Biology of Reproduction, 54, 1375-1382.

Tyler, C.R. (1994). Developmental expression and modulation of the vitellogenin receptor in ovarian follicles of the rainbow trout, Oncorhynchus mykiss. Journal of Experimental Zoology, 269, 458-466.

Nagler, J.J. Pottinger, T.P. Turner, M. (1994). Effects of unilateral ovariectomy on recruitment and growth of follicles in the rainbow trout, Oncorhynchus mykiss. Fish Physiology and Biochemistry, 13, 309-316.

Purdom CE, Hardiman PA, Bye VJ, Eno NC, Tyler CR, Sumpter JP (1994). Estrogenic Effects of Effluents from Sewage Treatment Works. Chemistry and Ecology, 8(4), 275-285. Abstract.

Hardiman, P.A. Bye, V. Eno, N.C. (1994). Oestrogenic effects of effluent from sewage treatment works. Chemistry and Ecology, 8, 275-285.

Tyler, C.R. Sumpter, J.P. (1994). Ovarian follicles of rainbow trout (Oncorhynchus mykiss) cultured within lamellae survive well, and sequester and process vitellogenin. Journal of Experimental Zoology, 269, 45-52.

Tyler, C.R. (1993). Electrophoretic patterns of yolk proteins throughout ovarian development and their relationship to vitellogenin in the rainbow trout, Oncorhynchus mykiss. Comparative Biochemistry and Physiology Part B, 106, 321-329.

Everett, S. (1993). Gross morphological disorders in barbel (Barbus barbus) in three rivers in southern England. Journal of Fish Biology, 43, 739-748.

Tyler CR, Everett S (1993). Incidences of gross morphological disorders in barbel (Barbus barbus) in three rivers in southern England. Journal of Fish Biology, 43(5), 739-748. Abstract.

Tyler CR, Lancaster P (1993). Isolation and characterization of the receptor for vitellogenin from follicles of the rainbow trout, Oncorhynchus mykiss. Journal of Comparative Physiology B, 163(3), 225-233. Abstract.

Tyler CR, Sumpter JP, Kawauchi H, Swanson P (1991). Involvement of gonadotropin in the uptake of vitellogenin into vitellogenic oocytes of the rainbow trout, Oncorhynchus mykiss. Gen Comp Endocrinol, 84(2), 291-299. Abstract. Author URL.

Sumpter, J.P. Campbell, P.M. (1991). Uptake of vitellogenin into oocytes during early vitellogenic development in the rainbow trout, Oncorhynchus mykiss (Walbaum). Journal of Fish Biology, 38, 681-689.

Tyler CR, Sumpter JP, Bromage NR (1990). An in vitro culture system for studying vitellogenin uptake into ovarian follicles of the rainbow trout, Salmo gairdneri. Journal of Experimental Zoology, 255(2), 216-231. Abstract.

Sumpter, J.P. (1990). The development of a radioimmunoassay for carp, Cyprinus carpio, vitellogenin. Fish Physiology and Biochemistry, 8, 129-140.

Tyler CR, Sumpter JP, Witthames PR (1990). The dynamics of oocyte growth during vitellogenesis in the rainbow trout (Oncorhynchus mykiss). Biol Reprod, 43(2), 202-209. Abstract. Author URL.

Tyler CR, Sumpter JP, Handford RM (1990). The dynamics of vitellogenin sequestration into vitellogenic ovarian follicles of the rainbow trout, Salmo gairdneri. Fish Physiology and Biochemistry, 8(3), 211-219. Abstract.

Sumpter, J.P. (1990). The purification and partial characterisation of carp, Cyprinus carpio, vitellogenin. Fish Physiology and Biochemistry, 8, 111-120.

TYLER CR, SUMPTER JP, BROMAGE NR (1988). INVIVO OVARIAN UPTAKE AND PROCESSING OF VITELLOGENIN IN THE RAINBOW-TROUT, SALMO-GAIRDNERI. JOURNAL OF EXPERIMENTAL ZOOLOGY, 246(2), 171-179. Author URL.

TYLER CR, SUMPTER JP, BROMAGE NR (1988). SELECTIVITY OF PROTEIN SEQUESTRATION BY VITELLOGENIC OOCYTES OF THE RAINBOW-TROUT, SALMO-GAIRDNERI. JOURNAL OF EXPERIMENTAL ZOOLOGY, 248(2), 199-206. Author URL.

Sumpter, J.P. Bromage, N.R. (1988). The selectivity of protein sequestration by vitellogenic oocytes of the rainbow trout, Salmo gairdneri, in vivo. Journal of Experimental Zoology, 248, 199-206.

TYLER C, SUMPTER J, BROMAGE N (1987). THE SPECIFICITY OF VITELLOGENIN UPTAKE INTO OVARIAN FOLLICLES OF RAINBOW-TROUT, SALMO-GAIRDNERI. JOURNAL OF ENDOCRINOLOGY, 112, 50-50. Author URL.

TYLER C, SUMPTER J, BROMAGE N (1987). VITELLOGENIN UPTAKE BY CULTURED OOCYTES OF RAINBOW-TROUT (SALMO-GAIRDNERI). GENERAL AND COMPARATIVE ENDOCRINOLOGY, 66(1), 19-20. Author URL.

Chapters

Tyler CR, Goodhead RM (2010). Impacts of hormone-disrupting chemicals on wildlife. In (Ed) Silent Summer: the State of Wildlife in Britain and Ireland, 125-140. Abstract.

Routledge, E. van Aerle, R. (2008). Estrogenic effects of treated sewage effluent on fish: steroids and surfactants in English rivers. In DiGiulio R, Hinton D (Eds.) The Toxicology of Fishes.

Tyler CR, Filby AL, van Aerle R, Lange A, Ball J, Santos EM (2008). Fish toxicogenomics. In (Ed) Advances in Experimental Biology, Elsevier.

Filby AL, Tyler CR, Iguchi T, Kramer V, Larsson DGJ, van Leewen K, Viant M, Tillit DE (2007). Application of genomics to tiered testing. In (Ed) Molecular Biology and Risk Assessment: Evaluation of the Potential Roles of Genomics in Regulatory Ecotoxicology, SETAC Press, 33-62.

Thorpe KL, Tyler CR (2004). Estrogenic effects of the alkylphenol ethoxylates andtheir biodegradation products. In (Ed) Handbook of Detergents, Part B: Environmental Impact, 447-466. Abstract.

Conferences

Goodhead RM, Johnston BD, Cole PA, Baalousha M, Hodgson D, Iguchi T, Lead JR, Tyler CR (2015). Does natural organic matter increase the bioavailability of cerium dioxide nanoparticles to fish?. Abstract.

Cross RK, Tyler C, Galloway TS (2015). Transformations that affect fate, form and bioavailability of inorganic nanoparticles in aquatic sediments. Abstract.

Moreman J, Lee O, Kudoh T, Tyler CR (2012). Application of ERE-transgenic biosensor zebrafish to identify target tissues and effect mechanisms of the environmental estrogen, bisphenol A. Author URL.

Lange A, Sebire M, Rostkowski P, Horwood J, Miyagawa S, Mizutani T, Iguchi T, Hill EM, Tyler CR (2012). Bioavailable environmental antiandrogens and their potential effects on endpoints relevant to reproduction in fish. Author URL.

Tyler CR, Hamilton PB, Lange A, Filby AL, Soffkar M, Lee O, Takesono A, Kudoh T, Paull GC, Iguchi T, et al (2012). Health impacts of exposure to environmental oestrogens in fish. Author URL.

Filby AL, Paull GC, Searle F, Ortiz-Zarragoitia M, Tyler CR (2012). Investigating the mechanisms by which environmental oestrogens affect male aggression and dominance hierarchies in fish. Author URL.

Al-Sahli R, Abdul-Sada A, Lange A, Tyler CR, Hill EM (2012). The xenometabolome and novel contaminant biomarkers in fish exposed to a wastewater treatment works effluent. Author URL.

Southam AD, Hines A, Viant MR, Lange A, Tyler CR, Hill EM (2010). A metabolomic investigation to identify molecular changes induced in roach after exposure to the anti-androgen organophosphate pesticide fenitrothion. Author URL.

Corcoran J, Lange A, Tyler CR, Winter MJ (2010). Investigating drug-metabolising cytochrome P450 (cyp) isoforms in a fish hepatocyte model. Author URL.

Gaiser BK, Fernandes TF, Jepson M, Lead JR, Tyler CR, Stone V (2009). Assessing exposure, uptake and toxicity of silver and cerium dioxide nanoparticles from contaminated environments. Abstract.

Tyler C, Lange A, Santos E, Coe T, Paull G, Filby A, Hamilton P (2008). The feminization of fish in English rivers: Causation, mechanisms, and significance. Author URL.

Jobling S, Tyler CR (2003). Endocrine disruption, parasites and pollutants in wild freshwater fish. Abstract. Author URL.

Kirk LA, Tyler CR, Lye CM, Sumpter JP (2002). Changes in estrogenic and androgenic activities at different stages of treatment in wastewater treatment works. Abstract. Author URL.

Tyler CR, Ball J, Maack G, Paull G, Santos EM (2002). Endocrine disruption in vertebrate wildlife - Today's story. Author URL.

Schulz RW, Vischer HF, Cavaco JEB, Santos EM, Tyler CR, Goos HJT, Bogerd J (2001). Gonadotropins, their receptors, and the regulation of testicular functions in fish. Author URL.

Flammarion P, Brion F, Babut M, Garric J, Migeon B, Noury P, Thybaud E, Palazzi X, Tyler CR (2000). Induction of fish vitellogenin and alterations in testicular structure: Preliminary results of estrogenic effects in chub (Leuciscus cephalus). Abstract.

Internet publications

Filby AL, van Aerle R, Duitman J, Tyler CR (2008). The kisspeptin/gonadotropin-releasing hormone pathway and molecular signaling of puberty in fish. Biol Reprod, 78(2), 278-289.

The mechanisms underlying the initiation of puberty in fish are poorly understood, and whether the Kiss1 receptor (Kiss1r; previously designated G protein-coupled receptor 54; GPR54) and its ligands, kisspeptins, play a significant role, as has been established in mammals, is not yet known. We determined (via real-time PCR) temporal patterns of expression in the brain of kiss1r, gnrh2, and gnrh3 and a suite of related genes in the hypothalamo-pituitary-gonadal (HPG) axis and analyzed them against the timing of gonadal germ cell development in male and female fathead minnow (Pimephales promelas). Full- or partial-length cDNAs for kiss1r (736 bp), gnrh2 (698 bp), and gnrh3 (804 bp) cloned from fathead minnow were found to be expressed only in the brain, testis, and ovary of adult fish. Localization of kiss1r, gnrh2, and gnrh3 within the brain provided evidence for their physiological roles and a likely hypophysiotropic role for GnRH3 in this species (which, like other cyprinids, does not appear to express gnrh1). In both sexes, kiss1r expression in the brain increased at the onset of puberty and reached maximal expression in males when spermatagonia type B appeared in the testis and in females when cortical alveolus-stage oocytes first appeared in the ovary, the timings of which differed for the two sexes. However, kiss1r expression was considerably lower during more advanced stages of spermatogenesis and oogenesis. The expression of kiss1r closely aligned with that of the gnrh genes (gnrh3 in particular), suggesting the Kiss1r/kisspeptin system in fish has a similar role in puberty to that occurring in mammals, and this hypothesis was supported by the induction of gnrh3 (2.25-fold) and kiss1r (1.5-fold) in early-mid pubertal fish injected with mammalian kisspeptin-10 (2 nmol/g wet weight). An intriguing finding, and contrasting that in mammals, was an elevated expression of esr1, ar, and cyp19a2 (genes involved in sex steroid signaling) in the brain at the onset of puberty, and in females slightly in advance of the elevation in the expression of kiss1r.

Abstract. Author URL.

Publications by year

In Press

Le Page G, Gunnarsson L, Snape J, Tyler CR (In Press). Antibiotic risk assessment needs to protect both environmental and human health. Environ Int, 115, 397-399. Author URL.

Abstract. Full text.

Stevens CH, Croft DP, Paull, Tyler (In Press). Stress and welfare in ornamental fishes: what can be learned from aquaculture?. Jounral of Fish Biology Full text.

Edenbrow M, Bleakley BH, Darden SK, Tyler CR, Ramnarine IW, Croft DP (In Press). The evolution of cooperation: Interacting phenotypes among social partners. The American Naturalist Full text.

2019

Windsor FM, Durance I, Horton AA, Thompson RC, Tyler CR, Ormerod SJ (2019). A catchment-scale perspective of plastic pollution. Glob Chang Biol

Abstract. Author URL.

Pinion J (2019). Concordant spatio-temporal patterns of brain activation in zebrafish exposed to compounds with similar pharmacodynamics or with similar seizurogenic potential.

Abstract
Drug development is a highly resource intensive process that uses large numbers of animals for assessing the safety and efficacy of drugs prior to clinical testing. Improving the efficiency of drug development in terms of financial expenditure and number of animals used is therefore of utmost concern, not only to industry, but also to animal welfare organisations such as the NC3Rs. Poor efficiency in drug development largely stems from drug attrition, particularly attrition in the latter stages of the testing due to the large amount of resources expended at the point of failure. It is therefore imperative that deleterious off-target effects are identified as early as possible. However, typically, identification of seizure as a side-effect of drugs is performed in the later stages of development due to the highly intensive and low-throughput nature of seizure assays. At which point, if a compound fails, a large amount of resources have been squandered. There therefore exists a need for high-throughput and relatively inexpensive seizure liability assays that can be used early in drug development to prevent compounds destined for failure undergoing unnecessary resource intensive testing.
In this thesis we propose a refined approach using non-invasive imaging techniques in non-protected life stage zebrafish as a method for the detection of seizurogenic compounds early in drug development. In addition, we highlight its utility for elucidating the pharmacodynamics of compounds. In this study, a transgenic zebrafish line containing a GCaMP6s calcium sensor under the control of the pan-neuronal promoter elavl3 was used for functional profiling of compounds with varied pharmacologies. Light sheet microscopy was used to record fluorescent activity in three spatial dimensions over time (4-dimensions) from the zebrafish brain after exposure to forty-three different compounds with varied pharmacodynamics and seizure liability profiles. Hierarchical clustering was employed in order to assess if compounds with seizurogenic activity or similar pharmacodynamics elicited specific functional brain activity. It was found that compounds with dopaminergic and serotonergic mechanisms of action elicited highly specific and similar brain activity patterns and that non-seizurogenic drugs also clustered separately from seizurogenic ones. Subsequent analyses, focussed on the utilisation of machine learning techniques, developing a model that could be used to discriminate between compounds with and without potentially seizurogenic effects. It is clear, from the analyses presented here, that drugs do in fact elicit specific brain patterns in zebrafish and that these brain patterns are effectively detected using light sheet microscopy. This system is highly applicable for use within the drug industry and even in its relatively preliminary stages provided an accurate method of discriminating between compounds based on their physiological effects in zebrafish.

Abstract. Full text.

Windsor FM, Tilley RM, Tyler CR, Ormerod SJ (2019). Microplastic ingestion by riverine macroinvertebrates. Science of the Total Environment, 646, 68-74. Abstract.

Tyler CR, Parsons A, Rogers NJ, Lange A, Brown AR (2019). Plasticisers and Their Impact on Wildlife. Abstract.

2018

Lee CJ, Tyler CR, Paull GC (2018). Can simple tank changes benefit the welfare of laboratory zebrafish Danio rerio?. J Fish Biol, 92(3), 653-659. Abstract. Author URL.

Holder PJ, Jones A, Tyler C, Cresswell J (2018). Holder et al (PNAS): Datasets for dietary exposures of mixed-age honey bees to fipronil, imidacloprid, thiamethoxam and cypermethrin. Abstract. Full text.

2017

Abstract. Author URL. Full text.

2016

2015

Orton F, Tyler CR (2015). Do hormone-modulating chemicals impact on reproduction and development of wild amphibians?. Biol Rev Camb Philos Soc, 90(4), 1100-1117.

Abstract. Author URL.

Jennings V, Goodhead R, Tyler CR (2015). Ecotoxicology of Nanomaterials in Aquatic Systems. , 8, 3-45. Abstract.

Abstract. Author URL.

Heindel JJ, Newbold RR, Williams CJ, Iguchi T, Tyler CR (2015). Lou Guillette--in memorandum. Mol Reprod Dev, 82(10), Fmi-v. Author URL.

Cross RK, Tyler C, Galloway TS (2015). Transformations that affect fate, form and bioavailability of inorganic nanoparticles in aquatic sediments. Abstract.

Lee O, Green JM, Tyler CR (2015). Transgenic fish systems and their application in ecotoxicology. Crit Rev Toxicol, 45(2), 124-141. Abstract. Author URL.

2014

Abstract. Author URL.

Baker TJ, Tyler CR, Galloway TS (2014). Impacts of metal and metal oxide nanoparticles on marine organisms. Environmental Pollution, 186, 257-271. Abstract.

Baker TJ, Tyler CR, Galloway TS (2014). Impacts of metal and metal oxide nanoparticles on marine organisms. Environ Pollut, 186, 257-271. Abstract. Author URL.

Abstract.

2013

Abstract.

2012

Baalousha M, Ju-Nam Y, Cole PA, Hriljac JA, Jones IP, Tyler CR, Stone V, Fernandes TF, Jepson MA, Lead JR, et al (2012). Characterization of cerium oxide nanoparticles-Part 2: Nonsize measurements. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 31(5), 994-1003. Author URL.

Lee O, Tyler CR, Kudoh T (2012). Development of a transient expression assay for detecting environmental oestrogens in zebrafish and medaka embryos. BMC Biotechnol, 12

Abstract. Author URL. Full text.

Tyler CR, Hamilton PB, Lange A, Filby AL, Soffkar M, Lee O, Takesono A, Kudoh T, Paull GC, Iguchi T, et al (2012). Health impacts of exposure to environmental oestrogens in fish. Author URL.

Croft DP, Hamilton PB, Darden SK, Jacoby DMP, James R, Bettaney EM, Tyler CR (2012). The role of relatedness in structuring the social network of a wild guppy population. Oecologia, 1-9.

Al-Sahli R, Abdul-Sada A, Lange A, Tyler CR, Hill EM (2012). The xenometabolome and novel contaminant biomarkers in fish exposed to a wastewater treatment works effluent. Author URL.

2011

Fabrega J, Luoma SN, Tyler CR, Galloway TS, Lead JR (2011). Silver nanoparticles: behaviour and effects in the aquatic environment. Environ Int, 37(2), 517-531. Abstract. Author URL.

2010

Abstract.

Tyler CR, Goodhead RM (2010). Impacts of hormone-disrupting chemicals on wildlife. In (Ed) Silent Summer: the State of Wildlife in Britain and Ireland, 125-140. Abstract.

Corcoran J, Lange A, Tyler CR, Winter MJ (2010). Investigating drug-metabolising cytochrome P450 (cyp) isoforms in a fish hepatocyte model. Author URL.

Scown TM, van Aerle R, Tyler CR (2010). Review: Do engineered nanoparticles pose a significant threat to the aquatic environment?. Crit Rev Toxicol, 40(7), 653-670. Abstract. Author URL.

Filby AL, Paull GC, Hickmore TF, Tyler CR (2010). Unravelling the neurophysiological basis of aggression in a fish model. BMC Genomics, 11

Abstract. Author URL.

2009

Gaiser BK, Fernandes TF, Jepson M, Lead JR, Tyler CR, Stone V (2009). Assessing exposure, uptake and toxicity of silver and cerium dioxide nanoparticles from contaminated environments. Abstract.

Thorpe KL, Maack G, Benstead R, Tyler CR (2009). Estrogenic wastewater treatment works effluents reduce egg production in fish. Environ Sci Technol, 43(8), 2976-2982. Abstract. Author URL.

Bickley LK, Lange A, Winter MJ, Tyler CR (2009). Evaluation of a carp primary hepatocyte culture system for screening chemicals for oestrogenic activity. Aquat Toxicol, 94(3), 195-203.

Abstract. Author URL.

Paull GC, Filby AL, Tyler CR (2009). Growth rate during early life affects sexual differentiation in roach (Rutilus rutilus). Environmental Biology of Fishes, 85(4), 277-284. Abstract.

Abstract. Author URL.

2008

Benstead, R. Eccles, P. Maack, G. (2008). Effective assessment of the oestrogenic activity of effluents using a laboratory flow-through exposure system. Aquatic Toxicology

Routledge, E. van Aerle, R. (2008). Estrogenic effects of treated sewage effluent on fish: steroids and surfactants in English rivers. In DiGiulio R, Hinton D (Eds.) The Toxicology of Fishes.

van Aerle R, Kille P, Lange A, Tyler CR (2008). Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish. Peptides, 29(1), 57-64. Abstract. Author URL.

Tyler CR, Filby AL, van Aerle R, Lange A, Ball J, Santos EM (2008). Fish toxicogenomics. In (Ed) Advances in Experimental Biology, Elsevier.

Johnston, B.J. Tyler, C.R. (2008). Imaging metal oxide nanoparticles in biological structures with CARS microscopy. Optical Express, 16(5), 3408-3419.

Handy RD, Henry TB, Scown TM, Johnston BD, Tyler CR (2008). Manufactured nanoparticles: their uptake and effects on fish--a mechanistic analysis. Ecotoxicology, 17(5), 396-409.

Abstract. Author URL.

Tyler CR, Jobling S (2008). Roach, sex, and gender-bending chemicals: the feminization of wild fish in English rivers. BioScience, 58(11), 1051-1059. Abstract.

Kille, P. Workman, V.L. Paull, G.C. (2008). Sexually dimorphic gene expression in the brains of mature zebrafish. Comparative Biochemistry and Physiology Part A

Tyler C, Lange A, Santos E, Coe T, Paull G, Filby A, Hamilton P (2008). The feminization of fish in English rivers: Causation, mechanisms, and significance. Author URL.

Filby AL, van Aerle R, Duitman J, Tyler CR (2008). The kisspeptin/gonadotropin-releasing hormone pathway and molecular signaling of puberty in fish. Biol Reprod, 78(2), 278-289.

Abstract. Author URL.

2007