Person
Nash, Jon
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Biography and Research Interest
We have recently been successful in obtaining a research grant to study the effect of pollutants on the reproduction of Zebrafish. I will be collaborating with Jon Nash.
The project is titled:
Endocrine disruption of fish reproductive physiology by steroidogenic xenobiotics and transgenerational consequences to reproductive success.
Pollution is causing deleterious effects on fish reproduction through disruption of the endocrine system. Some of these reproductive dysfunctions are caused by chemicals that are oestrogen and androgen receptor antagonists or agonists, interfering with normal receptor binding of sex steroids. Previous studies fail to investigate the mechanisms of endocrine disruption at different sites along the hypothalamus-pituitary-gonad axis and throughout all stages of development. They also fail to relate reproductive endocrine perturbations to reductions in reproductive success. The aim of my research will be to address the question of whether there is any consequence to reproductive success from steroidogenic xenobiotics and if there is, what are the mechanisms of action. I propose to use the zebra danio (Brachydanio rerio) as a model to test the following hypotheses: 1. Certain xenobiotics are oestrogen and androgen receptor antagonists or agonists, interfering with normal binding of sex steroids at multiple sites and stages of development, 2. the degree and type of interference will be dependant on the xenobiotics binding characteristics, amount and time of exposure, site of action, stage of development and current endocrine status, 3. that these interferences will cause perturbations to the endocrine system which will compromise sexual function, 4. these sexual dysfunctions will have deleterious consequences on reproductive success, 5. perturbations to the ypothalamus-pituitary-gonad axis at sensitive stages could have the greatest consequences, for example, during early sexual differentiation, 6. sexual dysfunction could be transgenerational, and 7. the type and timing of these reproductive failures will effect the level of impact to the population. Breeding colonies of danios will be chronically exposed to a range of concentrations (within environmentally realistic limits) of three types of steroidogenic xenobiotics: ethynylestradiol, alkylphenol polyethoxylates, DDT and its metabolites. Reduction in reproductive success will ultimately be quantified by measuring the number of viable and sexually integral offspring. Therefore, not only will the survival of the F1 generation be measured but also their reproductive potential (F2 numbers). Various molecular, cellular, endocrine and observational methods will be utilised to disseminate the mechanisms of how these steroidogenic xenobiotic interfere with receptors in sensitive areas of the reproductive axis and how this causes reproductive dysfunctions. The results of these controlled laboratory experiments will, I hope, form a valuable contribution to the knowledge of how certain pollutants can interfere directly with the reproductive physiology of fish and have consequential repercussions on their reproductive fitness. My work will then provide a firm scientific basis for evaluating the impact of steroidogenic pollution on wild fish populations.
The project is titled:
Endocrine disruption of fish reproductive physiology by steroidogenic xenobiotics and transgenerational consequences to reproductive success.
Pollution is causing deleterious effects on fish reproduction through disruption of the endocrine system. Some of these reproductive dysfunctions are caused by chemicals that are oestrogen and androgen receptor antagonists or agonists, interfering with normal receptor binding of sex steroids. Previous studies fail to investigate the mechanisms of endocrine disruption at different sites along the hypothalamus-pituitary-gonad axis and throughout all stages of development. They also fail to relate reproductive endocrine perturbations to reductions in reproductive success. The aim of my research will be to address the question of whether there is any consequence to reproductive success from steroidogenic xenobiotics and if there is, what are the mechanisms of action. I propose to use the zebra danio (Brachydanio rerio) as a model to test the following hypotheses: 1. Certain xenobiotics are oestrogen and androgen receptor antagonists or agonists, interfering with normal binding of sex steroids at multiple sites and stages of development, 2. the degree and type of interference will be dependant on the xenobiotics binding characteristics, amount and time of exposure, site of action, stage of development and current endocrine status, 3. that these interferences will cause perturbations to the endocrine system which will compromise sexual function, 4. these sexual dysfunctions will have deleterious consequences on reproductive success, 5. perturbations to the ypothalamus-pituitary-gonad axis at sensitive stages could have the greatest consequences, for example, during early sexual differentiation, 6. sexual dysfunction could be transgenerational, and 7. the type and timing of these reproductive failures will effect the level of impact to the population. Breeding colonies of danios will be chronically exposed to a range of concentrations (within environmentally realistic limits) of three types of steroidogenic xenobiotics: ethynylestradiol, alkylphenol polyethoxylates, DDT and its metabolites. Reduction in reproductive success will ultimately be quantified by measuring the number of viable and sexually integral offspring. Therefore, not only will the survival of the F1 generation be measured but also their reproductive potential (F2 numbers). Various molecular, cellular, endocrine and observational methods will be utilised to disseminate the mechanisms of how these steroidogenic xenobiotic interfere with receptors in sensitive areas of the reproductive axis and how this causes reproductive dysfunctions. The results of these controlled laboratory experiments will, I hope, form a valuable contribution to the knowledge of how certain pollutants can interfere directly with the reproductive physiology of fish and have consequential repercussions on their reproductive fitness. My work will then provide a firm scientific basis for evaluating the impact of steroidogenic pollution on wild fish populations.
Non-Zebrafish Publications