Grantee Research Project Results
1997 Progress Report: Environmental Xenoestrogens and Reproductive Toxicity in Fish
EPA Grant Number: R823450Title: Environmental Xenoestrogens and Reproductive Toxicity in Fish
Investigators: Benson, William H.
Institution: University of Mississippi
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1995 through September 1, 1997
Project Period Covered by this Report: October 1, 1996 through September 1, 1997
Project Amount: $224,295
RFA: Exploratory Research - Environmental Biology (1995) RFA Text | Recipients Lists
Research Category: Biology/Life Sciences , Environmental Justice , Human Health , Aquatic Ecosystems
Objective:
The purpose of this project was to investigate the effects of environmental xenoestrogens in fish and to examine the potential of estrogenic activity to affect populations by means of reproductive and developmental toxicity. The project was designed to test the hypothesis that mammalian xenoestrogens are also estrogenic in fish by virtue of direct interaction with the teleostean estrogen receptor. Biological indicators of estrogenicity were assessed in vivo by examining the appearance of vitellogenin (VTG) in serum. In addition, the binding of suspected xenoestrogens to the estrogen receptor was determined using in vitro binding competition studies. Both in vivo and in vitro experiments allowed for comparison of estrogenic potency to 17 -estradiol (E2). The hypothesis that estrogenic activity precedes reproductive impairment was examined using Japanese medaka. Fish were exposed to xenoestrogens and mated to assess changes in fecundity and viability of eggs and larvae. Finally, a field study explored the use of diagnostic assays of estrogenic activity to identify environmental contamination.Progress Summary:
In screening experiments, sexually immature catfish were exposed to E2, suspected xenoestrogens or combination doses of E2 and xenoestrogen. Appearance of VTG in serum was used as the bioindicator of estrogenicity. Synthetic estrogens, ethinylestradiol, mestranol and diethylstilbestrol were effective in inducing VTG; the antiestrogen tamoxifen inhibited response to E2 when given in a combination dose. Treatment with both methoxychlor and p-nonylphenol resulted in VTG appearance in serum; the doses required were 300 times that of E2 and the vitellogenic response was less when compared to the E2- induced response. In addition, a combination dose of methoxychlor with E2 decreased the magnitude of the response to E2. Other mammalian xenoestrogens, o,p'-DDT, chlordecone, lindane and -HCH, were not able to produce a vitellogenic response.Studies were conducted to examine the affinity of xenoestrogens for hepatic catfish estrogen receptor in vitro. A significantly greater number of binding sites were observed with E2 (156 fmoles/mg protein) and p-nonylphenol (126 fmoles/mg protein) treatments, as compared to control (71 fmoles/mg protein). Treatment with E2 resulted in a significantly increased apparent Kd value (2.5 nM) compared to control (1.4 nM).
The reproductive toxicity of two xenoestrogens, identified in the screening experiments discussed above, was evaluated in Japanese medaka. Larval medaka were exposed to methoxychlor (1, 4, 16 ppb), p- nonylphenol (0.5, 2, 8 ppb) and E2 (0.1, 1, 10 ppb). Each of the three exposures, which were conducted separately, included a control and solvent (acetone) control. With E2 treatment, 100% of surviving fish in all doses were female as compared to 50% in controls. Reproductive capability of the female fish, resulting from E2 treatment, was assessed by pairing females with naive males and monitoring spawning. These females, some of which were genetic males, did not have impaired spawning capacity.
In the field study, municipal wastewater was screened for estrogenic effects in channel catfish by examining the induction of VTG. At two municipal wastewater treatment plants (WWTPs) up to a four- fold induction of vitellogenin was observed, as compared to the reference site. Microsomal liver enzymes, cytochrome P4501A1, are traditionally used as indicators of polyaromatic hydrocarbons and PCB exposure, and where significantly elevated at each WWTP, compared to reference sites.
Future Activities:
U.S. Environmental Protection Agency, Office of Research and Development (Grant Submission), $366,001. "Characterization of the structure and function of sex steroid hormone receptors from the Japanese medaka (Oryzias latipes)" (Co-Principal Investigator, 5% effort), 1998-2001.U.S. Environmental Protection Agency, Office of Research and Development (Grant Submission), $435,193. "Use of a transgenerational model to evaluate threshold effects of environmental chemicals in fish" (Co-Principal Investigator, 10% effort), 1998-2001.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
| Other project views: | All 5 publications | 5 publications in selected types | All 4 journal articles |
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Nimrod AC, Benson WH. Estrogenic responses to xenobiotics in channel catfish (Ictalwus punctatus). Marine Environmental Research 1996;42(1-4):155-160. |
R823450 (1997) |
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Nimrod AC, Benson WH. Xenobiotic interaction with and alteration of channel catfish estrogen receptor. Toxicology and Applied Pharmacology 1997;147(2):381-390. |
R823450 (1997) |
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Nimrod AC, Benson WH. Reproduction and development of Japanese medaka following an early life stage exposure to xenoestrogens. Aquatic Toxicology 1998;44(1-2):141-156. |
R823450 (1997) |
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Schlenk D, Stresser DM, McCants JC, Nimrod AC, Benson WH. Influence of β-naphthoflavone and methoxychlor pretreatment on the biotransformation and estrogenic activity of methoxychlor in channel catfish (Ictalurus punctatus). Toxicology and Applied Pharmacology 1997;145(2):349-356. |
R823450 (1997) |
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Supplemental Keywords:
Water, chemicals, environmental toxicology, reproduction, development., RFA, Health, Scientific Discipline, Toxics, Environmental Chemistry, Endocrine Disruptors - Environmental Exposure & Risk, pesticides, Chemistry, endocrine disruptors, Risk Assessments, Endocrine Disruptors - Human Health, Biology, channel catfish, endocrine disrupting chemicals, animal model, developmental effects, Japanese medaka, vitellogenin, Methoxychlor, DDT, reproductive health, biomarker, xenoestrogensRelevant Websites:
http://www.olemiss.edu/depts/rips/echr.html
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.