Paternal Residential Exposure to Unconventional Oil and Gas Drilling (UOG) - Unconventional oil and natural gas (UOG) extraction combines directional drilling and hydraulic fracturing or “fracking.” Over 1000 UOG chemicals (UOGCs) are used across the industry, and the waste water contains an additional 599 chemicals. Hundreds of these are known or suspected endocrine disrupting chemicals (EDCs). UOG operations cause air pollution and contamination of surface and ground water, exposing nearby humans by inhalation, dermal contact, and/or ingestion. Approximately 18 million Americans (5% of the population) live within 1 mile of a UOG site. Robust studies have reported birth defects in newborns with mothers residing near UOG activities, but failed to separate maternal and paternal exposure. A systematic review found only six high quality articles evaluating male occupational exposure to petroleum operations; none included exposure to UOG. Recent work has highlighted the importance of paternal exposures not only to fertility but also to pregnancy outcomes and offspring health. Environmentally relevant concentrations of chemicals detected in surface and ground water near UOG sites acted as EDCs in a human cell line in vitro, in adult female mice, and in prenatally exposed male and female mice. This prior work suggests the potential for adverse reproductive outcomes in humans exposed to UOGCs, and serves as the rationale for the hypothesis: residential proximity of men to UOG operations is associated with urinary biomarkers of exposure, disruption of reproductive hormones, decreased sperm production, and damage to sperm chromosomes. In a pilot study, UOGCs were elevated in the urine of residentially exposed humans. For example, trans,trans-muconic acid (ttMA), a benzene metabolite, was detected at levels almost 5 times higher than seen in the general population, and higher than prior reports for occupational petroleum exposure. In this proposed study, 240 men of reproductive age will be recruited, half in areas rich in UOG operations (< 5 miles) and half in nearby areas devoid of these activities (> 25 miles). Participants will collect urine and semen, and will complete questionnaires to assess demographics and exposures. Urine will be evaluated for UOGCs, their metabolites and reproductive hormones using high-resolution mass spectrometry. Participants will measure sperm motility using an FDA-approved phone app, and sperm count, morphology, DNA integrity and histone methylation will be measured in the laboratory. Outcomes: UOGC levels, hormone levels, and sperm measures, adjusted for questionnaire-derived factors, will be compared between exposed and unexposed men. Exposure will be calculated from home and work addresses, time spent at each location, and geocoded UOG well locations using inverse distance weighted well counts. Multivariable models will evaluate relationships between exposure and outcomes, adjusting for confounding variables. Completion of the proposed study will dramatically increase the understanding of UOGC exposure and male reproductive health; and will inform both healthcare providers and the UOG industry residential exposure and toxicity.
