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

遗传和环境因素对人类女性减数分裂前期的影响

基本信息

批准号：
10584398
负责人：
TERRY J HASSOLD
金额：
$ 48.91万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-22 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584398
关键词：
Adult Affect Aneuploidy Biological Monitoring Blood Circulation Cell Cycle Regulation Characteristics Chemical Exposure Chemicals Chromatin Chromosome Pairing Chromosome abnormality Chromosomes Cohort Analysis Conceptions Congenital Abnormality Data Databases Development Endocrine Disruptors Endogenous Factors Environmental Exposure Environmental Risk Factor Event Exhibits Exogenous Factors Exposure to Failure Female Fetal Development Fetus Frequencies Generations Genetic Genetic Nondisjunction Genetic Recombination Genetic Variation Genotype Human Incidence Individual Laboratories Length Maternal Age Maternal Exposure Meiosis Meiotic Recombination Metabolic Methods Nature Oocytes Oogenesis Ovary Pathway interactions Phenotype Placenta Pregnancy Prophase Resources Sampling Serum Spontaneous abortion Synaptonemal Complex Testing Urine Variant Work base bisphenol A cohort design egg exposed human population fascinate fetal human female insight inter-individual variation phthalates placental transfer prenatal exposure stem

项目摘要

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.

项目概要我们对人类胎儿卵巢进行的减数分裂研究十多年来产生了最大的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 2008年至2017年收集的每个样本的生物样本，这是一个生物样本快速变化的时期内分泌干扰化学 (EDC) 污染物的光谱和水平。拟议的研究将检验以下假设：人类女性的高减数分裂错误率是由天生的错误倾向（例如，由于雌性减数分裂的长期性和雌性减数分裂的差异）细胞周期控制）和环境因素。我们假设环境引起的影响将会被辨别出来，因为它们扰乱了明确的减数分裂关系。我们将扩大我们的该群体的减数分裂数据库并描述了人类已知原因的特征非整倍体，重组失败。每个病例的减数分裂曲线与暴露相结合概况将用于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。我们还将获得有关人类时间变化的数据暴露于常见内分泌干扰化学 (EDC) 污染物并比较能力不同的 EDC 从母体循环转移到发育中的胎儿。