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.

项目概要 据估计，全球约 15% 的夫妇受到不孕症的影响，其中 40% 的不孕症由男性因素造成 每年只有约 10% 的美国育龄女性怀孕，并且只有约 60% 的人能够怀孕。 尽管越来越多的夫妇使用医疗治疗，但预期怀孕的人数却在减少。 因此，确定可改变的因素，例如。 可能影响人类生育能力的环境暴露是一个重大的临床和公共卫生问题。 水果和蔬菜是美国普通人群接触非持久性污染物的主要来源 农药，与不同的不良健康影响有关，包括不孕不育、生殖障碍 疾病、妊娠和围产期并发症虽然已被证明与父亲的环境有关。 暴露可能会影响精子表观基因组和由此产生的后代健康，没有流行病学研究表明 迄今为止，已经探讨了父亲接触农药对怀孕和围产期的影响以及潜在的生物学影响 为了解决这些重要的知识差距，我们的目标是确定解释这些关联的机制。 男性尿液中农药生物标志物浓度（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（目标 1），与怀孕和 根据女性尿液农药生物标志物（目标 2）以及表观遗传衰老来调整围产期结局 精液和白细胞的表观遗传年龄或 DNA 甲基化衰老生物标志物最近出现。 与年龄相关的疾病（例如不孕症和生殖健康）的优秀生物标志物来检查这些。 为了实现新的目标，我们将利用两个前往生育中心的潜在夫妇群体：环境和 马萨诸塞州波士顿的生殖健康 (EARTH) 研究（主要研究）和精子环境表观遗传学 和发展研究（SEEDS），在马萨诸塞州斯普林菲尔德（验证研究）。 了解相对较少研究的男性生殖领域的非职业农药接触 健康，还将开辟一个重要的调查领域，以更好地了解父亲的环境如何 暴露会影响夫妇和后代的健康以及将父系关系联系起来的潜在生物机制 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）致力于推进环境健康科学，包括 我们目前正在收集对环境化学品的共同暴露和个人敏感性。 针对参与 EARTH 研究的夫妇所生孩子的详细健康措施 确定父亲和母亲受孕前环境暴露的相关程度 结合神经发育和代谢终点的评估。 农药类别将提供可在未来儿童健康结果研究中联系起来的数据。