Mechanisms of Bisphenol A Effects on Female Meiosis

Washington State University, Pullman WA

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Abstract

? DESCRIPTION (provided by applicant): Over 90% of Americans are exposed daily to the industrial plasticizer bisphenol A (BPA) through oral (food packaging) and transdermal (thermal receipts) routes. Clinical studies have correlated BPA exposure with reduced fertility in men and women, yet how BPA elicits these effects is unknown. Recent studies in mice indicate that BPA exposure during early meiosis in females causes a 20% increase in aneuploid eggs, representing a serious threat to mammalian fertility. The goal of the research outlined in this proposal is to elucidate the biochemical pathway linking BPA exposure to the observed meiotic abnormalities. Previous studies indicate that BPA interferes with estrogen receptor-mediated signaling to influence meiosis; therefore, the studies in this application will assess the role of oocyte estrogen pathways in mediating the effects of BPA exposure on meiosis. Furthermore, these studies will identify changes in oocyte gene expression that result from BPA exposure downstream of estrogen signaling. Understanding the specific signal transduction pathways utilized by BPA in oocytes will be pertinent to female fertility and may be extrapolated to understand the etiology of BPA-related diseases in other cell types. Finally, the proposed studies will investigate at the molecular level how BPA exposure changes chromosome organization during meiosis. Abnormal chromosome organization during early meiotic stages frequently results in aneuploidy, a leading cause of pregnancy loss in humans. The combined results of these studies will clarify the health risks of BPA exposure in mammals.