ToxSci Advance Access originally published online on December 20, 2007
Toxicological Sciences 2008 102(2):371-382; doi:10.1093/toxsci/kfm306
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Published by Oxford University Press 2007.
Gestational and Lactational Exposure to Ethinyl Estradiol, but not Bisphenol A, Decreases Androgen-Dependent Reproductive Organ Weights and Epididymal Sperm Abundance in the Male Long Evans Hooded Rat
* U. S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Reproductive Toxicology Division, Endocrinology Branch, Research Triangle Park, North Carolina 27711
Department of Zoology, North Carolina State University, Raleigh, North Carolina 27695
1 To whom correspondence should be addressed. Fax: (919) 541-4017. E-mail: howdeshell.kembra{at}epa.gov.
Received October 11, 2007; accepted December 11, 2007
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Abstract |
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Many chemicals released into the environment are capable of disrupting normal sex steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive organ development in laboratory animals; however, effects of lower doses of these chemicals have been debated. The goal of the current study was to determine whether relatively low oral doses of EE or BPA would alter male reproductive morphology and associated hormone levels of Long Evans hooded rat. Dams were gavaged with corn oil vehicle, EE (0.05–50 µg/kg/day) or BPA (2, 20, and 200 µg/kg/day) during pregnancy through lactation from gestational day 7 to postnatal day (PND) 18. Anogenital distance was measured at PND2 and nipple retention was measured at PND14 in male pups. Male offspring were euthanized beginning at PND150, and sera and organs were collected for analyses. Adult body weight was significantly decreased in males exposed to 50 µg EE/kg/day. Developmental EE exposure reduced androgen-dependent tissue weights in a dose-dependent fashion; for example, seminal vesicle and paired testes weights were reduced with 
5 µg EE/kg/day. Epididymal sperm counts were also significantly decreased with 50 µg EE/kg/day. In contrast, treatment with 2, 20, or 200 µg BPA/kg/day or EE at 0.05–1.5 µg/kg/day did not significantly affect any male endpoint in the current study. These results demonstrate that developmental exposure to oral micromolar doses of EE can permanently disrupt the reproductive tract of the male rat.
Key Words: ethinyl estradiol; bisphenol A; male reproduction; Long Evans rat; testes; epididymal sperm.
Disclaimer: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and has been approved for publication. Approval does not necessarily reflect the views and policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.