Environmental Xenoestrogens and Reproductive Toxicity in FishEPA Grant Number: R823450
Title: Environmental Xenoestrogens and Reproductive Toxicity in Fish
Investigators: Benson, William H.
Institution: University of Mississippi Main Campus
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1995 through September 1, 1997
Project Amount: $224,295
RFA: Exploratory Research - Environmental Biology (1995) RFA Text | Recipients Lists
Research Category: Biology/Life Sciences , Economics and Decision Sciences , Health , Ecosystems
Description:The purpose of this project is to investigate the effects of environmental xenoestrogens in teleosts and to examine the potential of estrogenic activity to affect populations by means of reproductive and developmental toxicity. The project is designed to test the hypothesis that mammalian xenoestrogens are also estrogenic in fish by virtue of direct interaction with the teleostean estrogen receptor. To accomplish this, channel catfish (Ictalarus punctatus) and Japanese medaka (Oryzias latipes) will be exposed to known or suspected mammalian xenoestrogens including o,p'-DDT, methoxychlor, hexachlorocyclohexane, endosulfan, p-nonylphenol, mestranol and ethynyl estradiol. Biological indicators of estrogenicity will be assessed in vivo by examining the appearance of vitellogenin in serum. In addition, the binding of suspected xenoestrogens to the estrogen receptor will be determined using in vitro binding competition studies. Both in vivo and in vitro experiments will allow comparison of estrogenic potency to that of 17 -estradiol. Through disruption of the endocrine system, xenoestrogens may be detrimental to both vitellogenesis and spermatogenesis. The genetic determination of the gonadal gender and phenotype of teleosts can be overridden by administration of exogenous sex steroids during the developmental period. Therefore, early exposure to xenoestrogens may alter development and result in hermaphroditism or sex reversal. Co-administration of estradiol and xenoestrogens to channel catfish will test the hypothesis that xenoestrogens interfere with the ability of estradiol to induce vitellogenesis. The hypothesis that estrogenic activity precedes reproductive impairment will be tested using Japanese medaka. Adult females will be exposed to xenoestrogens and paired with naive male fish to assess changes in fecundity, egg size and viability of eggs and larvae. After reaching maturity, reproductive capacity will be assessed and gonadal development will be examined histologically. Finally, a field study will explore the use of estrogenic biomarkers to identify environmental contamination.
This investigation seeks to explore the underlying mechanisms of reproductive toxicity due to select compounds which disrupt the endocrine system. The anthropogenic compounds which have been proven, or are suspected of being xenoestrogens and endocrine disrupters include chlorinated hydrocarbon pesticides, degradation products of high-use industrial surfactants, by-products of industrial processes such as paper pulp mills, potent synthetic estrogens used in estrogen-replacement therapy and oral contraceptive formulations which find their way to the environment through municipal sewage. An added benefit of this research is that it will contribute to the growing knowledge base of alternative bioassays for estrogenic activity. Furthermore, environmental xenoestrogens may interfere with biological systems at the molecular level and can have far-reaching consequences at the organismal and population level. In the final phase of the proposed investigation, estrogenic responses will be used as indicators of exposure to environmental xenoestrogens in field studies.