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

项目总结 我们对人类胎儿卵巢进行了十多年的减数分裂研究，产生了最大规模的 现有的人类女性减数分裂数据库。这一独特的资源包括匹配的母亲/胎儿 2008年至2017年收集的每个样本的生物量，在这段时间里， 内分泌干扰物(EDC)污染物的范围和水平。建议进行的研究 将检验这一假设，即人类女性的高减数分裂错误率是由 与生俱来的错误倾向(例如，由于雌性减数分裂的长期性质和 细胞周期控制)和环境因素。我们假设环境诱导的影响 将是可辨别的，因为它们扰乱了明确定义的减数分裂关系。我们将扩大我们的 减数分裂数据库的队列和特征的一个众所周知的人类病因的特征 非整倍体，重组失败。与暴露有关的每个病例的减数分裂特征 将利用资料来确定胎儿暴露是否以及如何影响女性的早期阶段 人类生殖系发育。我们还将获得人类时间变化的数据 暴露在常见的内分泌干扰物(EDC)污染物中并比较其能力 不同的内分泌细胞从母体循环传递到发育中的胎儿。

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.