Bisphenol A and Ovotoxicity

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Bisphenol A (BPA) is an endocrine disrupting chemical that is widely used in polycarbonate plastics such as food packaging products, milk containers, baby bottles, liners for food cans, and dental materials. The widespread use of BPA raises concerns because developmental and postnatal exposures to BPA have been linked to female infertility in a variety of species. While BPA exposure causes infertility in a variety of species, the reasons for BPA-induced infertility are unknown. Preliminary data suggest that BPA may cause infertility by inhibiting growth and inducing death (atresia) of ovarian follicles. Further, preliminary data indicate that BPA may cause infertility by inhibiting the production of estradiol (E2) by the ovary. Little other information is available on the effects of BPA on ovarian function. The study planned by the National Center for Toxicologic Research/Food and Drug Administration (NCTR/FDA) offers a perfect opportunity to examine the effects of BPA on the ovary. The NCTR/FDA design can easily be expanded to measure the effects of BPA on ovarian follicle growth, atresia, follicle numbers, E2 levels, infertility, and premature ovarian failure. Specifically, the proposed work will expand the NCTR/FDA study by testing the hypothesis that BPA exposure inhibits follicle growth and induces atresia, leading to low E2 levels followed by infertility and/or premature ovarian failure. To test this hypothesis, the following specific aims will be completed: 1) determine if BPA exposure reduces follicle numbers by inhibiting follicle growth and/or inducing atresia in rat ovaries, 2) determine if BPA exposure reduces E2 levels by inhibiting E2 synthesis and/or by increasing E2 metabolism in rat ovaries, and 3) determine the ability of BPA exposure to cause infertility and premature ovarian failure in the adult rat. The proposed work will increase our understanding ofthe mechanisms by which BPA causes ovotoxicity. It is important to understand the mechanisms by which BPA damages the ovary because this may lead to the development of novel targets for the treatment of low E2 levels, infertility, and premature ovarian failure induced by BPA.