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

费尔纳德社区队列中生殖伴侣的铀暴露与不孕症 项目摘要 不孕不育是一个具有国家和国际意义的公共卫生问题。除了基因，解剖学， 内分泌和医学原因、化学和金属暴露越来越多地被调查为 男性和女性不孕不育的危险因素。该项目旨在调查与以下物质有关的铀暴露 费尔纳德社区队列中的人类不孕不育(FCC)。该项目利用了约9000人的优势 FCC，其成员生活在1951-1989年经历过铀暴露的社区， 医疗监测项目的参与者。年度问卷数据收集和定期生物检疫 在铀加工设施关闭后，自1991年以来进行了收集。史无前例的 FCC的研究资源将提供一个独特的机会来调查铀暴露及其 对不孕不育的贡献。我们假设在环境中长期暴露于铀与 FCC中生殖伴侣不孕不育风险增加，这种关联是由交替调节的 生殖激素：抗苗勒氏激素(AMH)和睾酮(T)。研究目标为：目标1： 费尔南德地区铀暴露与男女不孕症的关系 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学用于 在所有约9000名参与者中进行疾病控制和预防(CDC)，以检查#年不孕症的相关性 队列中的男性和女性。目的2：确定生殖激素水平的不同变化 费尔纳德社区队列成员中的不孕不育和铀暴露对照病例。在……里面 为了达到这个目的，我们将使用不孕期前获得的血清，测定女性的AMH和男性的T 病例和对照，并在嵌套病例对照方法中使用这些测量来检查相关性 铀暴露和生殖激素之间的关系。这将阐明可能的激素机制。 铀与不孕症的关系。在针对性别的分析中，激素和铀暴露都将被检查。 对于它们与不孕不育的关系，然后将其纳入不孕不育的调解分析。该项目 将由苏珊·平尼博士与辛辛那提大学和该大学的同事合作领导 将填补生殖和发育毒性信息的一个重要数据空白 在环境暴露水平下暴露于铀。网站上提供的大量问卷和临床数据 病例和对照，结合激素分析数据，可能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的极大兴趣 监管机构。

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.