Uranium Exposure and Infertility in Reproductive Partners in the Fernald Community Cohort

Fernald 社区队列中生殖伴侣的铀暴露和不孕症

• 批准号: 10666344
• 负责人: Susan Mengel Pinney
• 金额: $ 20.26万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10666344
• 关键词: Anatomy; Animals; Apoptosis; Biological; Birth; Cadmium; Cell Density; Centers for Disease Control and Prevention (U.S.); Chemical Exposure; Chemicals; Chromosomal Instability; Chronic; Cleft Palate; Clinical Data; Collaborations; Collection; Communities; Congenital Abnormality; Data; Data Analyses; Data Collection; Department of Energy; Developmental Process; Digestion; Endocrinology; Environmental Exposure; Environmental Health; Exposure to; Female; Female infertility; Fetal Weight; Fetus; Genetic; Germ Cells; Gonadal structure; Health; Hematoma; Hormonal; Hormones; Human; Infertility; International; Knowledge; Lesion; Longitudinal cohort; Male Infertility; Maternal Exposure; Measurement; Measures; Mediating; Mediation; Medical; Metal exposure; Metals; Mining; Monitor; Mus; Navajo; Necrosis; Nitrates; Nuclear Reactors; Outcome; Ovarian Follicle; Participant; Pennsylvania; Periodicals; Persons; Physiologic Ossification; Policy Making; Population; Pregnancy Rate; Prevention; Process; Production; Public Health; Questionnaires; Radial; Rattus; Reporting; Research; Resources; Risk; Risk Factors; Sampling; Serum; Site; Source; Spermatocytes; Tail; Testis; Testosterone; Toxicology; Universities; Uranium; Weight; Woman; bone; case control; cohort; cranium; design; developmental toxicity; dosimetry; experience; experimental study; fetal; high risk; human study; interest; male; malformation; member; men; mullerian-inhibiting hormone; novel; offspring; operation; programs; reproductive; reproductive function; reproductive hormone; reproductive toxicity; sex; uranyl acetate; wasting

Uranium Exposure and Infertility in Reproductive Partners in the Fernald Community Cohort Project Summary Infertility is a public health issue with national and international significance. Besides genetic, anatomical, endocrinological, and medical causes, chemical and metal exposures have been increasingly investigated as risk factors for both male and female infertility. This project aims to investigate uranium exposure in relation to human infertility in the Fernald Community Cohort (FCC). The project takes advantage of the ~9000-person FCC, whose members lived in a community that experienced uranium exposure from 1951-1989 and were participants in a medical monitoring program. Yearly questionnaire data collection and periodic biospecimen collection were conducted since 1991, after the closure of the uranium processing facility. The unprecedented research resource in the FCC will provide a unique opportunity to investigate uranium exposure and its contribution to infertility. We hypothesize that chronic environmental exposure to uranium is associated with increased risk of infertility in reproductive partners in the FCC, and the association is mediated by alternations of reproductive hormones: anti-müllerian hormone (AMH) and testosterone (T). The research aims are: Aim 1: To investigate the association between uranium exposure and male and female infertility in the Fernald Community Cohort. In a longitudinal cohort design, we will use uranium dosimetry generated by Centers for Disease Control and Prevention (CDC) in all ~9000 participants to examine the association with infertility in males and females in the cohort. Aim 2: To identify differential changes in reproductive hormone levels in cases of infertility and controls, by uranium exposure, in members of the Fernald Community Cohort. In this Aim, using serum obtained prior to the period of infertility, we will measure AMH in female and T in male cases and controls, and use those measurements in a nested case-control approach to examine the association between uranium exposure and reproductive hormones. This will elucidate potential hormonal mechanisms of uranium in relation to infertility. In sex-specific analyses, both hormones and uranium exposure will be examined for their relationship to infertility, and then will be incorporated into mediation analyses of infertility. The project will be led by Dr. Susan Pinney in collaboration with colleagues at the University of Cincinnati and the University of Pennsylvania and will fill an important data gap of information in reproductive and developmental toxicity from exposure to U at environmental exposure levels. The extensive questionnaire and clinical data available on cases and controls, combined with the hormone analysis data, may provide clues to the mechanism of altered reproductive function. The findings will be of great interest to the environmental health science community and regulatory agencies.

Fernald社区队列中生殖伴侣的铀暴露和不孕症 项目摘要 不孕症是一个具有国家和国际意义的公共卫生问题。除了遗传学解剖学 内分泌和医疗原因，化学和金属暴露越来越多地被调查， 男性和女性不育的危险因素。该项目旨在调查与以下方面有关的铀暴露： Fernald社区队列（FCC）中的人类不育症。该项目利用约9000人的 FCC的成员生活在一个社区，从1951年到1989年经历了铀暴露， 参与医疗监测项目。年度问卷数据收集和定期生物样本 自1991年铀加工设施关闭以来，一直在进行收集工作。前所未有的 FCC的研究资源将提供一个独特的机会来调查铀暴露及其 对不孕症的贡献。我们假设长期环境暴露于铀与 FCC中生殖伴侣不孕不育的风险增加，并且这种关联是通过改变来介导的 生殖激素：抗苗勒管激素（AMH）和睾酮（T）。研究目的是：目的1： 探讨Fernald人群中铀暴露与男性和女性不育之间的关系， 社区队列在一个纵向队列设计中，我们将使用由中心产生的铀剂量， 疾病控制和预防中心（CDC）在所有约9000名参与者中检查了不孕症的相关性， 男性和女性在队列中。目的2：确定生殖激素水平的差异变化， Fernald社区队列成员中铀暴露的不孕症病例和对照。在 本研究的目的是利用不孕症前期的血清，检测女性AMH和男性T 病例和对照，并在嵌套的病例对照方法中使用这些测量来检查关联 铀暴露和生殖激素之间的关系这将阐明潜在的激素机制， 铀与不孕症的关系在性别特异性分析中，将检查激素和铀暴露 它们与不孕症的关系，然后将被纳入不孕症的调解分析。项目 将由Susan Pinney博士与辛辛那提大学和大学的同事合作领导 并将填补生殖和发育毒性信息的重要数据空白， 环境暴露水平的铀暴露。广泛的问卷调查和临床数据， 病例和对照，结合激素分析数据，可能提供改变的机制的线索， 生殖功能这些发现将引起环境健康科学界的极大兴趣， 监管机构。