Male pesticide exposure, reproductive health and epigenetics

男性农药接触、生殖健康和表观遗传学

• 批准号: 10733537
• 负责人: Lidia Minguez Alarcon
• 金额: $ 73.31万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733537
• 关键词: 2,4-Dichlorophenoxyacetic Acid; Acceleration; Acids; Address; Affect; Age; Aging; Agriculture; Alzheimer' s Disease; Area; Asthma; Biological; Biological Markers; Boston; Child; Child Health; Clinic; Clinical; Cohort Studies; Conceptions; Consumption; Couples; DNA Methylation; DNA copy number; Data; Development; Diabetes Mellitus; Disease; Eating; Environment; Environmental Exposure; Environmental Health; Epigenetic Process; Exposure to; Female; Female infertility; Fertility; Fertilization; Fertilization in Vitro; Fetal Growth; Fetal Reduction; Food; Future; General Population; Genomics; Health; Herbicides; High-Risk Pregnancy; Human; Individual; Infertility; Insecticides; Intake; Knowledge; Length; Leukocytes; Link; Live Birth; Low Birth Weight Infant; Male Infertility; Measures; Medical; Metabolic; Mitochondria; Mitochondrial DNA; Modification; Morphology; National Institute of Environmental Health Sciences; Nitrophenol; Organophosphates; Outcome; Parkinson Disease; Paternal Exposure; Perinatal; Pesticide Residues; Pesticides; Play; Predisposition; Pregnancy; Pregnancy loss; Prospective cohort; Public Health; Publications; Regulation; Reproductive Health; Research; Route; Sampling; Seminal fluid; Serum; Source; Tissues; United States Environmental Protection Agency; Urine; Woman; age related; cancer type; cell motility; cohort; dietary; environmental chemical; epidemiology study; epigenome; experience; food quality; fruits and vegetables; hydroxypyridine; implantation; male; men; molecular marker; novel; offspring; perinatal complications; perinatal outcomes; pesticide exposure; pregnant; prospective; pyrethroid; reproductive; reproductive system disorder; sperm cell; success; surveillance data; urinary; validation studies

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.

项目摘要 估计不育会影响全球所有夫妇的约15％，而男性因素占不育的40％ 在夫妻中。每年只有约10％的美国生殖年龄妇女怀孕，只有约60％是 打算怀孕。尽管越来越多地在夫妻中使用医疗 繁殖力，活产成功率保持稳定。那，确定可修改的因素，例如 环境暴露，可能影响人类生育能力是主要的临床和公共卫生问题。摄入量 美国一般人群中的水果和蔬菜是暴露于非持久性的主要来源 农药与不同的不良健康影响有关，包括不育，生殖 疾病，怀孕和围产期并发症。虽然已经表明父亲环境 暴露可能会影响精子的表观基因组和后代健康，没有流行病学研究 日期探索了父亲农药暴露和潜在生物学的怀孕和围产期作用 解释关联的机制。为了解决这些重要的知识差距，我们旨在确定 雄性尿液浓度的农药生物标志物（单独和作为混合物）与 精液参数，精子DNA甲基化和线粒体DNA生物标志物（AIM 1），怀孕和 调整女性尿尿农药生物标志物（AIM 2）的围产期结局（AIM 2），并且表观遗传衰老 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为 与年龄有关的疾病（例如不育和生殖健康）的出色生物标志物。检查这些 新颖的目的，我们将利用参加生育中心的两对前瞻性夫妇：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 与马萨诸塞州斯普林菲尔德的发展研究（种子）（验证研究）。拟议的研究将增加我们的 了解相对了解的男性生殖区域的非占有农药暴露 健康，还将为更好地理解父亲环境开辟一个重要的调查领域 暴露会影响夫妻和后代的健康和潜在的生物学机制 环境他的孩子的健康。最重要的是，该项目解决了国家的战略重点 环境健康科学研究所（NIEHS），用于推进环境健康科学，包括 评估共有和个人对环境化学物质的敏感性。我们目前正在收集 对参加地球研究的夫妇出生的儿童的详细健康措施 确定父亲和孕妇统一的环境暴露的程度 具有神经发育和代谢终点。结合了几个接触的评估 种类的农药将提供可以在未来有关儿童健康结果的研究中链接的数据。