bisphenol a exposure in utero disrupts early oogenesis in the mouse早期接触双酚a在子宫内破坏卵子发生的老鼠.pdf

Bisphenol A Exposure In Utero Disrupts Early Oogenesis in the Mouse 1,2 2 1,3 2* Martha Susiarjo , Terry J. Hassold , Edward Freeman , Patricia A. Hunt 1 Department of Genetics, Case Western Reserve University, Cleveland, Ohio, United States of America, 2 School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America, 3 Department of Biology, St. John Fisher College, Rochester, New York, United States of America Estrogen plays an essential role in the growth and maturation of the mammalian oocyte, and recent studies suggest that it also influences follicle formation in the neonatal ovary. In the course of studies designed to assess the effect of the estrogenic chemical bisphenol A (BPA) on mammalian oogenesis, we uncovered an estrogenic effect at an even earlier stage of oocyte development—at the onset of meiosis in the fetal ovary. Pregnant mice were treated with low, environmentally relevant doses of BPA during mid-gestation to assess the effect of BPA on the developing ovary. Oocytes from exposed female fetuses displayed gross aberrations in meiotic prophase, including synaptic defects and increased levels of recombination. In the mature female, these aberrations were translated into an increase in aneuploid eggs and embryos. Surprisingly, we observed the same constellation of meiotic defects in fetal ovaries of mice homozygous for a targeted disruption of ERb, one of the two known estrogen receptors. This, coupled with the finding that BPA exposure elicited no additional effects in ERb null females, suggests that BPA exerts its effect on the early oocyte by interfering with the actions of ERb. Together, our results show that BPA can influence early meiotic events and, importantly, indica