Paternal Residential Exposure to Unconventional Oil and Gas Drilling (UOG)

非常规石油和天然气（UOG）开采结合了定向钻井和水力压裂， “水力压裂”整个行业使用超过1000种UOG化学品（UOGC），废水中含有 599化学品其中数百种是已知或疑似的内分泌干扰物（EDCs）。 UOG作业造成空气污染以及地表水和地下水污染，使附近的人类暴露 通过吸入、皮肤接触和/或摄入。约1800万美国人（占人口的5%） 居住在UOG站点1英里范围内。强有力的研究报告说， 居住在UOG活动附近，但未能区分母亲和父亲的暴露。一项系统性综述发现， 只有6篇高质量的文章评价男性职业暴露于石油作业;没有包括 暴露于UOG。最近的研究强调了父亲接触的重要性，不仅对生育率， 也会影响怀孕结果和后代健康。与环境相关的化学品浓度 在UOG站点附近的地表水和地下水中检测到的内分泌干扰物在体外人体细胞系中起作用，在成人中 雌性小鼠以及产前暴露的雄性和雌性小鼠。这项先前的工作表明， 暴露于UOGC的人类的不良生殖结果，并作为假设的基本原理： 男性与UOG操作的住宅接近度与暴露的尿生物标志物相关， 生殖激素紊乱，精子生成减少，精子受损 染色体在一项初步研究中，居民接触者尿液中的UOGC升高。为 例如，反式，反式粘康酸（ttMA），一种苯代谢物，被检测到的水平几乎高出5倍 高于一般人群，也高于以往报告的职业性石油暴露。 在这项拟议的研究中，将招募240名育龄男性，其中一半在UOG业务丰富的地区（< 5 英里），一半在附近没有这些活动的地区（> 25英里）。参与者将收集尿液和精液， 并将完成问卷调查，以评估人口统计学和暴露。将对尿液进行UOGC评价， 他们的代谢物和生殖激素使用高分辨率质谱。参与者将 使用FDA批准的手机应用程序测量精子活力，以及精子计数、形态、DNA完整性和 将在实验室中测量组蛋白甲基化。结局：UOGC水平、激素水平和精子 将对暴露和未暴露的测量值进行比较， 男人暴露将根据家庭和工作地址、在每个地点花费的时间和地理编码进行计算 使用反距离加权井数的UOG井位置。多变量模型将评估 暴露和结果之间的关系，调整混杂变量。完成 拟议的研究将大大增加对UOGC暴露和男性生殖健康的理解; 并将告知医疗保健提供者和UOG行业的住宅暴露和毒性。

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.