Male pesticide exposure, reproductive health and epigenetics

项目摘要 据估计，全世界约15%的夫妇患有不孕症，男性因素占不孕症的40 在夫妻之间。每年只有约10%的美国育龄妇女怀孕， 有意怀孕。尽管越来越多的夫妇使用医疗， 生育率、活产成功率保持稳定。因此，确定可修改的因素，如 环境暴露可能影响人类生育能力，是一个重大的临床和公共卫生问题。摄入 水果和蔬菜是美国普通人群接触非持久性有机污染物的主要来源。 农药，它已与不同的不利健康影响，包括不育，生殖 以及妊娠和围产期并发症。虽然已经表明，父亲的环境 暴露可能会影响精子表观基因组，从而影响后代的健康，没有流行病学研究， 日期已经探讨了怀孕和围产期的影响，父亲农药暴露和潜在的生物 解释关联的机制。为了解决这些重要的知识差距，我们的目标是确定 男性尿中农药生物标志物浓度（单独和混合）与 精液参数，精子DNA甲基化和线粒体DNA生物标志物（目的1），妊娠和 调整女性尿农药生物标志物（aim 2）的围产期结局，以及 精液和白细胞表观遗传年龄或DNA甲基化衰老生物标志物最近出现， 与年龄有关的疾病，如不孕症和生殖健康的优秀生物标志物。审查这些 新的目标，我们将利用两个前瞻性队列的夫妇参加生育中心：环境和 马萨诸塞州波士顿的生殖健康（地球）研究（主要研究）和精子环境表观遗传学 和开发研究（SEEDS）（验证研究）。建议的研究将增加我们的 对男性生殖健康研究相对不足的非职业性农药暴露的理解 健康，也将打开一个重要的调查领域，以更好地了解如何父亲的环境 暴露可能会影响夫妇和后代的健康，以及将父亲与母亲联系在一起的潜在生物机制。 环境对孩子的健康。最重要的是，该项目涉及国家战略优先事项， 环境健康科学研究所（NIEHS），促进环境健康科学，包括 评估共同接触和个人对环境化学品的敏感性。我们目前正在收集 对参加地球研究的夫妇所生子女的详细健康措施， 确定父亲和母亲孕前环境暴露的相关程度 神经发育和代谢终点。对接触几种有害物质的评估 各类杀虫剂将提供数据，可用于今后有关儿童健康结果的研究。

PROJECT SUMMARY Infertility is estimated to affect ~15% of all couples worldwide and male factors account for 40% of infertility among couples. Only ~10% of U.S. reproductive age women get pregnant each year and only ~60% are intended pregnancies. Despite the increasing use of medical treatment among couples with decreased fecundity, success rates of live birth have remained stable. Thus, identifying modifiable factors, such as environmental exposures, that can impact human fertility is a major clinical and public health matter. Intake of fruits and vegetables in the U.S. general population is the primary source of exposure to non-persistent pesticides, which has been associated with different adverse health effects, including infertility, reproductive disorders, and pregnancy and perinatal complications. While it has been shown that paternal environmental exposures may impact the sperm epigenome and consequently offspring health, no epidemiological studies to date have explored pregnancy and perinatal effects of paternal pesticide exposure and potential biological mechanisms that explain the associations. To address these important knowledge gaps, we aim to determine the association of male urinary concentrations of pesticide biomarkers (individually and as a mixture) with semen parameters, sperm DNA methylation and mitochondrial DNA biomarkers (aim 1), with pregnancy and perinatal outcomes adjusting for female urinary pesticide biomarkers (aim 2), and also with epigenetic aging in semen and leukocytes. Epigenetic age or DNA methylation aging biomarkers have recently emerged as excellent biomarkers of age-related diseases such as infertility and reproductive health. To examine these novel aims, we will leverage two prospective cohorts of couples attending fertility centers: the Environment and Reproductive Health (EARTH) Study in Boston, MA (main study), and the Sperm Environmental Epigenetics and Development Study (SEEDS) in Springfield, MA (validation study). The proposed study will increase our understanding of non-occupational pesticide exposure for a relatively understudied area of male reproductive health and will also open an important area of inquiry into better understanding of how paternal environmental exposures can impact couples’ and offspring’s health and potential biologic mechanisms linking the paternal environment to his children’s health. Most importantly, this project addresses strategic priorities of the National Institute of Environmental Health Sciences (NIEHS) for advancing environmental health sciences, including assessing coexposures and individual susceptibility to environmental chemicals. We are currently collecting detailed health measures on children who were born to couples who participated in the EARTH Study to determine the extent to which paternal and maternal preconception environmental exposures are associated with neurodevelopmental and metabolic endpoints. Incorporating the assessment of exposure to several classes of pesticides will provide data that can be linked in future studies on children’s health outcomes.