The impact of genetic and environmental factors on meiotic prophase in the human female

点击翻译按钮获取中文摘要

PROJECT SUMMARY Meiotic studies of human fetal ovaries we conducted for over a decade have generated the largest available human female meiotic database. This unique resource includes matched maternal/fetal biospecimens for each sample collected from 2008 to 2017, a period of rapid changes in both the spectrum and levels of endocrine disrupting chemical (EDC) contaminants. The proposed studies will test the hypothesis that the high meiotic error rate in the human female is driven by both an innate propensity to error (e.g., due to the protracted nature of female meiosis and differences in cell cycle control) and environmental factors. We postulate that environmentally-induced effects will be discernable because they disturb well-defined meiotic relationships. We will expand our meiotic database for the cohort and characterize the features of a well-known cause of human aneuploidy, recombination failure. Meiotic profiles for each case in conjunction with exposure profiles will be used to determine if and how fetal exposure affects the early stages of female germline development in humans. We also will obtain data on temporal changes in human exposure to common endocrine disrupting chemical (EDC) contaminants and compare the ability of different EDCs to transit from the maternal circulation to the developing fetus.