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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES013527-10
Application #
8663691
Study Section
Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
Program Officer
Heindel, Jerrold
Project Start
2005-06-06
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
10
Fiscal Year
2014
Total Cost
$509,289
Indirect Cost
$127,930
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
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Baier, Brian; Hunt, Patricia; Broman, Karl W et al. (2014) Variation in genome-wide levels of meiotic recombination is established at the onset of prophase in mammalian males. PLoS Genet 10:e1004125
Vandenberg, Laura N; Hunt, Patricia A; Myers, John Peterson et al. (2013) Human exposures to bisphenol A: mismatches between data and assumptions. Rev Environ Health 28:37-58
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