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.

项目总结 据估计，全世界约15%的夫妇受到不孕症的影响，40%的不孕症是由男性因素造成的 在情侣之间。每年只有10%的美国育龄妇女怀孕，只有60%的人怀孕 有意怀孕。尽管患有癌症的夫妇越来越多地接受医疗治疗，但 繁殖力、活产成功率保持稳定。因此，确定可修改的因素，如 环境暴露会影响人类生育能力，这是一个重大的临床和公共卫生问题。摄入量 美国普通人群中的水果和蔬菜是接触非持久性 杀虫剂与不同的不良健康影响有关，包括不孕、生殖 疾病、妊娠和围产期并发症。虽然事实表明，父亲的环境 暴露可能会影响精子表观基因组，从而影响后代健康，没有流行病学研究 Date研究了父亲接触杀虫剂对怀孕和围产期的影响以及潜在的生物学效应 解释这些关联的机制。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(目标1)，与妊娠和 女性尿中农药生物标志物的围产儿结局调整(目标2)，也与表观遗传年龄有关 精液和白细胞。表观遗传年龄或DNA甲基化老化生物标记物最近出现为 与年龄有关的疾病，如不孕不育和生殖健康的极佳生物标志物。来研究这些 新的目标，我们将利用两个预期的夫妇队列去生育中心：环境和 马萨诸塞州波士顿生殖健康(地球)研究(主要研究)和精子环境表观遗传学 和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 对相对缺乏研究的男性生殖领域非职业性农药暴露的了解 并将开启一个重要的调查领域，以更好地了解父亲的环境 暴露可能会影响夫妇和子女的健康，并可能影响与父亲相关的生物机制 环境对他的孩子的健康有好处。最重要的是，该项目解决了国家 环境健康科学研究所(NIEHS)促进环境健康科学，包括 评估联合暴露和个人对环境化学品的敏感性。我们目前正在收集 对参与地球研究的夫妇所生子女的详细健康措施 确定父亲和母亲的先入为主的环境暴露之间的关联程度 神经发育和新陈代谢的终点。纳入对暴露于几种环境的评估 杀虫剂的类别将提供数据，这些数据可以在未来关于儿童健康结果的研究中联系起来。