Environmental estrogens (EEs) are a heterogenous group of chemicals containing natural and synthetic estrogens and xenoestrogens. EEs are pollutants of the freshwater environment and exert the biological activity of estrogenic hormones. Concern has been expressed over the possibility that EEs disrupt the endocrine regulation of reproduction in wildlife and/or humans, and the information available at present suggests that it is very plausible that EEs have such effects. However, the evidence that EEs constitute a real problem is meagre. Only when serious effects of EEs are recorded will it then be necessary to unravel the molecular mechanisms that govern these effects, and to develop strategies to manage EE-related risks. Therefore, the present proposal aims to evaluate EFFECTS of four relevant and representative EEs on the neuro-endocrine regulation of reproduction in freshwater fish. Reproduction in all vertebrates from fish to mammals is regulated by a neuro-endocrine system, the brain-pituitary-gonad (BGP) axis. Estrogens play a pivotal role in this regulatory system in both males and females. Previous work demonstrated that EEs induced, in male fish, the otherwise female-specific production of yolk proteins or inhibited testicular growth. However, also the brain-pituitary part of the BPG axis may be affected by EEs. After all, endogenous estrogens regulate the (i) amount of brain neurohormones involved in reproduction (e.g. gonadotropin releasing hormone - GnRH); (ii) expression and/or release of GnRH receptors and of gonadotropic hormone (GTH) by pituitary gonadotropin cells; (iii) testicular sex hormone synthesis. Effects of EEs on the core-components of the BPG axis are suspected to have a significant impact on reproduction because of possible consequences for sexual maturation and reproductive behaviour. We propose to investigate in male of three freshwater fishes the effects of exposure to EEs via the water on (i) GnRH amounts in brain and pituitary, (ii) pituitary GnRH receptors and GTH synthesis and release, and (iii) pituitary GnRH and testicular GTH responsiveness, thus covering core-components of the BPG axis. Finally, an immortalized fish gonadotropin cell line will be developed to provide an alternative to the use of experimental animals. Such a cell line is expected to serve well in future studies to test the endocrine-disrupting risks of EEs (and other pollutants) in a physiologically more meaningful context than is possible now with non-gonadotroph cell lines. The study can be carried out in a relatively short period (two years) as all expertise needed is available in the participating research groups.
Keywords: Environmental estrogens, fish reproduction, endocrine system, brain, pituitary, testis
Funding SchemeCSC - Cost-sharing contracts
69978 Tel Aviv