Early life environmental influences on gonadal health

About This Grant

PROJECT SUMMARY/ABSTRACT A growing body of evidence suggests that environmental exposures experienced early in life can cause a range of reproductive disorders later in life, such as those described in the ovarian and testicular dysgenesis syndrome hypotheses. Despite strong biological plausibility, very few human studies have evaluated how early life exposures to environmental factors may influence adult gonadal function. Moreover, the few existing studies have only focused on the earliest markers of gonadal health such as puberty and only examined the health effects associated with one environmental exposure at a time, ignoring the reality that individuals are exposed to multiple exposures simultaneously. This proposal takes a comprehensive approach to understanding the impact of a wide range of environmental factors on a variety of related but distinct gonadal health endpoints measured in adulthood. Our hypothesis is that higher cumulative exposure to chemical stressors (such as air pollution), physical stressors (such as temperature, noise and light at night, and ultraviolet radiation), and some aspects of the built environment (such as roadway proximity), and lower exposure to other features of the built and natural environment (such as greenness and walkability) during in utero and throughout early childhood will be associated with 1) disrupted menstrual cycle function in women and erectile dysfunction in men, 2) higher risk of infertility (time to pregnancy >12 months) in women and men, and 3) faster reproductive aging as assessed by a steeper decline in anti-Müllerian hormone levels in women and free testosterone levels in men. To test this hypothesis, we will use the unique resources of the Growing Up Today Study (GUTS). GUTS is a prospective cohort study of 27,706 children whose mothers are participants in the ongoing Nurses' Health Study II. They were first enrolled in 1996 (GUTS I) and 2004 (GUTS II) when the children were 9-15 years and all participants are currently 27-42 years. We will append information on multiple chemical stressors (particulate matter (PM2.5, PM10, PM2.5-10), NO2, ozone), physical stressors (temperature, humidity, noise, light at night, ultraviolet radiation), features of the built and natural environments (proximity to roadways, greenness, walkability) to the residential addresses of each participant from in utero throughout childhood. We will combine the environmental factors with time-varying data collected on social- (e.g. demographics, family and neighborhood socioeconomic status) and health-related behaviors (e.g. smoking, diet, physical activity, mental health) as well as inherent characteristics of the child (e.g. age, sex, race) and mother (e.g. smoking and multivitamin use during pregnancy) to comprehensively evaluate how environmental exposures experienced during early life impact gonadal function. We expect our findings to provide valuable information for individual- and population-level prevention, future risk assessments and policy decisions, having long-term impact on reducing adverse reproductive outcomes, and by extension other chronic health effects, in men and women.