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

• 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
• 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

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.

项目摘要 对我们进行了十多年的人类胎儿卵巢的减数分裂研究已经产生了最大的 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亲/胎儿 从2008年到2017年收集的每个样本的生物测量 频谱和内分泌破坏化学（EDC）污染物的水平。提出的研究 将检验以下假设，即人类女性的高度减数分裂错误率是由两者驱动的 先天性误差的倾向（例如，由于女性减数分裂的旷日持久性质和差异 细胞周期控制）和环境因素。我们假设环境引起的效果 将是可以辨别的，因为它们打扰了定义明确的减数分裂关系。我们将扩大我们的 该队列的减数分裂数据库并表征了人类的众所周知原因的特征 非整倍性，重组失败。每种情况下的减数分裂概况与暴露 轮廓将用于确定胎儿暴露是否以及如何影响女性的早期阶段 人类的种系发展。我们还将获得有关人类时间变化的数据 暴露于普通内分泌破坏化学（EDC）污染物并比较能力 不同的EDC从母体循环到发育中的胎儿。