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

项目摘要 我们对人类胎儿卵巢进行了十多年的减数分裂研究， 可用的人类女性减数分裂数据库。这种独特的资源包括匹配的母体/胎儿 从2008年到2017年收集的每个样本的生物标本，这是一个快速变化的时期， 内分泌干扰化学品（EDC）污染物的光谱和水平。拟议的研究 将测试这样一个假设，即人类女性的高减数分裂错误率是由两个因素驱动的， 先天的错误倾向（例如，由于女性减数分裂的长期性质和差异， 细胞周期控制）和环境因素。我们假设环境引起的影响 因为它们扰乱了明确的减数分裂关系。我们将扩大我们 减数分裂数据库的队列，并表征一个众所周知的原因，人类 非整倍性重组失败每例病例的减数分裂特征与暴露量 将使用特征来确定胎儿暴露是否以及如何影响女性的早期阶段。 人类的生殖细胞发育我们还将获得人类时间变化的数据， 暴露于常见的内分泌干扰化学品（EDC）污染物，并比较 不同的内分泌干扰物从母体循环转移到发育中的胎儿。

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.