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

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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.