Aneuploidy, the loss or gain of chromosomes, is the leading cause of human pregnancy failure and birth defects. Most aneuploidy arises from maternal nondisjunction, but its etiology remains obscure. Environmental factors have long been suspected to play a role but, until recently, this has not been substantiated by direct evidence. Recent studies in our laboratory suggest that exposure to the estrogenic chemical, bisphenol A (BPA) during pregnancy dramatically increases the frequency of chromosomally abnormal eggs and embryos in the mouse. Because humans are exposed to BPA on a daily basis, these findings have serious implications for human reproductive health. The studies outlined in this application will use mouse models to test the effects of fetal BPA exposure on reproductive lifespan in the female and examine the mechanisms by which BPA exerts its effects on the early stages of oogenesis. In addition, we will translate our findings from mice to humans by directly studying human fetal oocytes to determine if BPA similarly impacts early oogenesis in humans. Lastly, we will test the effect of genetic variation on the ability of biologically active BPA to reach specific tissues and on the tissue response to BPA. The combined data from these studies will enhance our understanding of the risk to human fertility posed by this chemical.
These studies will assess the effects on human reproductive health of bisphenol A (BPA), a member of a class of chemicals known as endocrine disrupting chemicals. Specifically, the studies outlined in this application focus on BPA-induced effects on gametogenesis in female mice and - for the first time - directly address the possibility that BPA exposure affects gamete production in humans as well.
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|Gerona, Roy R; Schwartz, Jackie M; Pan, Janet et al. (2018) Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry. J Expo Sci Environ Epidemiol 28:101-108|
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|Gruhn, Jennifer R; Al-Asmar, Nasser; Fasnacht, Rachael et al. (2016) Correlations between Synaptic Initiation and Meiotic Recombination: A Study of Humans and Mice. Am J Hum Genet 98:102-15|
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|Vrooman, Lisa A; Oatley, Jon M; Griswold, Jodi E et al. (2015) Estrogenic exposure alters the spermatogonial stem cells in the developing testis, permanently reducing crossover levels in the adult. PLoS Genet 11:e1004949|
|Rowsey, Ross; Gruhn, Jennifer; Broman, Karl W et al. (2014) Examining variation in recombination levels in the human female: a test of the production-line hypothesis. Am J Hum Genet 95:108-12|
|Vandenberg, Laura N; Gerona, Roy R; Kannan, Kurunthachalam et al. (2014) A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environ Health 13:25|
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