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: 10217328
• 负责人: Susan Mengel Pinney
• 金额: $ 25.86万
• 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/10217328
• 关键词: Anatomy; Animal Experimentation; 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; Environmental Exposure; Environmental Health; Exposure to; Female; Female infertility; Fetal Weight; Fetus; Genetic; Germ Cells; Gonadal structure; Health; Hematoma; Hormonal; Hormones; Human; Infertility; Institutes; 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; Periodicity; 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 Gain; 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社区队列中生殖伙伴的铀暴露和不育 项目摘要 不育是一个具有国家和国际意义的公共卫生问题。除了遗传，解剖学外， 内分泌学以及医学原因，化学和金属暴露已被增加，因为 男性和女性不育的危险因素。该项目旨在调查与 Fernald社区队列（FCC）中的人类不孕症。该项目利用了〜9000人 FCC的成员住在一个从1951 - 1989年经历铀暴露的社区中 医疗监测计划的参与者。年度调查表数据收集和定期生物测试 自1991年以来，在铀加工设施关闭后进行了收集。前所未有的 FCC中的研究资源将为调查铀暴露及其的独特机会 对不孕症的贡献。我们假设长期暴露于铀 FCC中生殖伴侣的不孕风险增加，该协会由替代方案介导 生殖激素：抗肿瘤激素（AMH）和睾丸激素（T）。研究目的是：目标1： 调查铀和女性不孕症在蕨类植物中的关联 社区队列。在纵向队列设计中，我们将使用中心生成的铀剂量法 所有约9000名参与者的疾病控制与预防（CDC）检查与不育症的关联 队列中的男性和女性。目标2：确定复制激素水平的差异变化 弗纳德社区队列的成员通过铀暴露的不育和控制病例。在 使用在不孕期之前获得的血清，我们将在雌性中测量AMH，而男性则将t。 案例和对照，并在嵌套的病例对照方法中使用这些测量来检查该关联 在铀暴露和繁殖激素之间。这将阐明潜在的激素机制 与不育有关的铀。在特定性别的分析中，将检查骑马和铀的暴露 因为它们与不育的关系，然后将其纳入不育的调解分析中。项目 将由苏珊·普尼（Susan Pinney）博士与辛辛那提大学和大学的同事合作。 宾夕法尼亚州的生殖和发育毒性信息的重要数据差距 在环境暴露水平上暴露于U。可用的广泛问卷和临床数据 案例和对照组结合了Horsene分析数据，可以为改变的机制提供线索 生殖功能。这些发现将引起环境健康科学界和 监管机构。