The horse as a sentinel for human reproductive and neurodevelopmental disorders associated with environmental chemical exposures

 描述(由申请人提供)：非常规天然气开发(UNGD)的快速发展速度超过了我们对其健康和环境影响的理解。居住在联合国国家工作队行动附近的个人和牲畜患有皮肤、上呼吸道、肌肉骨骼、胃肠道、生殖和中枢神经系统疾病。研究报告称，产妇居住在靠近UNGD手术的地方与先天缺陷、出生体重减轻和APGAR评分之间存在正相关。同样令人担忧的是，与UNGD相关的许多化学物质和金属与儿童的发育、学习和行为障碍有关。然而，缺乏将同时定性和定量环境化学物质暴露、孕产妇和胎儿/新生儿组织化学物质浓度与健康结果联系起来的研究。利用马动物模型作为人类健康的哨兵，我们将检验暴露在环境化学品中与新生儿神经缺陷和母亲生殖功能受损有关的假设。第一个具体目标是在两个独立的设施中，在18个月的繁殖周期中，对空气、水和牧草产生的环境化学物质进行量化，其中一个设施靠近联合国国家森林机构的作业，另一个(对照)设施位于未暴露的较远地点。 自然资源开采活动。使用战略部署在整个设施(空气、水)并由哨兵动物佩戴的被动采样装置(PSD)，将检测到多环和含氧芳香烃、挥发性有机化合物和杀虫剂。将对水和土壤抓取样本进行金属和微量元素分析；对牧草样本进行挥发性有机化合物分析；对饲料样本进行真菌毒素分析。第二个具体目标是量化动物组织中的环境化学品(在目标1中检测到)，并将它们的存在与器官功能障碍的发生联系起来，包括神经缺陷和生殖问题。在为期18个月的研究期间，将获取相关组织样本，以检测全身炎症、器官功能障碍、氧化应激、激素合成变化、新生儿神经发育异常和新生儿繁殖异常，以及新生儿出生体重和生长率下降的证据。我们的研究结果将建立环境化学品暴露与不良健康后果之间的联系，将为未来环境化学品暴露的病理生理机制的研究奠定基础。由于马非常适合作为人类疾病的动物模型，我们的研究结果和结论对在UNGD行动附近生活或工作的个人具有相关性。

 DESCRIPTION (provided by applicant): The rapid rate of unconventional natural gas development (UNGD) development is outpacing our understanding of its health and environmental impacts. Individuals and livestock residing in close proximity to UNGD operations experience disorders involving the skin, upper respiratory tract, the musculoskeletal, gastrointestinal, reproductive and central nervous systems. Studies report a positive association between maternal residential proximity to UNGD operations and the presence of congenital defects, reduced birth weights and APGAR scores. Equally worrisome is the finding that many of the chemicals and metals associated with UNGD are associated with developmental, learning and behavioral disabilities in children. Yet studies that have linked concurrent qualitative and quantitative environmental chemical exposures, maternal and fetal/neonatal tissue chemical concentrations and health outcomes are lacking. Utilizing an equine animal model as a sentinel for human health, we will test the hypothesis that exposure to environmental chemicals is associated with the development of neonatal neurological deficits and impaired maternal reproductive function. The first specific aim is to quantitate air-, water- and pasture forage-born environmental chemicals during an 18-month reproduction cycle at two separate facilities, one in close proximity to a UNGD operation and the other (control) facility at distant site not exposed to natural resource mining activities. Using passive sampling devices (PSDs) strategically deployed throughout the facilities (air, water) and worn by sentinel animals, polycyclic and oxygenated aromatic hydrocarbons, volatile organic compounds and pesticides will be detected. Water and soil grab samples will be analyzed for metals and trace elements; pasture forage samples will be analyzed for VOCs; feed samples will be analyzed for mycotoxins. The second specific aim is to quantitate environmental chemicals (detected in Aim 1) within animal tissues and correlate their presence with the development of with organ dysfunction, including neurological deficits and reproductive problems. Over the 18- month study period, relevant tissue samples will be obtained to detect evidence of systemic inflammation, organ dysfunction, oxidative stress, alterations in hormone synthesis, abnormalities in neonatal neural development and dam reproduction, and reduced neonatal birth weights and growth rates. The results of our study, which will establish a link between environmental chemical exposure-adverse health outcomes, will serve as the foundation of future investigations of the pathophysiological mechanisms of environmental chemicals exposure. Because the horse is well-suited as an animal model for human diseases, the results and conclusions of our study have relevance to individuals living or working in close proximity to UNGD operations.