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.