Human Pesticide Exposure and Epigenetic Changes in Sperm DNA

人类农药暴露与精子 DNA 的表观遗传变化

• 批准号: 9302776
• 负责人: TIMOTHY D HOWARD
• 金额: $ 35.71万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302776
• 关键词: 2,4-Dichlorophenoxyacetic Acid; Acids; Address; Adverse effects; Affect; Agriculture; Andrology; Area; Binding Proteins; Biological; Biological Markers; Centers for Disease Control and Prevention (U.S.); Chlorpyrifos; Chronic; Clinic; Controlled Study; DNA; DNA Methylation; Data; Environmental Impact; Environmental and Occupational Exposure; Epidemiology; Epigenetic Process; Exposure to; Family member; Fertility; Genes; Genome; Goals; Health; Health Policy; Herbicides; Human; Immigrant; Impairment; Individual; Infertility; Insecticides; Laboratory Animal Models; Latino; Methods; Methylation; Morphology; Occupational; Occupational Exposure; Occupations; Pattern; Pesticides; Population; Precipitation; Prevention strategy; Public Health; Publishing; Reporting; Reproductive Health; Research; Review Literature; Risk; Route; Seasons; Seminal fluid; Site; Sperm Count Procedure; Spermatogenesis; Time; United States; agricultural pesticide; base; case control; cell motility; clinically relevant; design; dichlorodiphenyltrichloroethane; epigenomics; experience; exposed human population; farm worker; genome wide methylation; genome-wide; imprint; longitudinal design; male; male health; men; men' s group; methylation pattern; next generation sequencing; pesticide exposure; public health relevance; pyrethroid; reproductive; socioeconomics; sperm cell; sperm function; sperm quality; urinary

 DESCRIPTION (provided by applicant): Human populations are exposed to a variety of pesticides. Much of the research documenting the detrimental effects of pesticide exposure on sperm quality has been extrapolated on laboratory and animal models with limited results from studies of direct human pesticide exposure. Many of the human studies focus on the use of persistent pesticides, such as DDT (dichlorodiphenyltrichloroethane), whose use is thankfully decreasing in the developed world. However, increasing studies suggest deleterious effects of contemporary, non-persistent pesticides on human semen parameters, including decreased sperm concentration and motility. Latino immigrant farmworkers, most of whom are men, are a health disparate population with direct and frequent exposure to pesticides. These men provide an opportunity to examine the mechanisms and effects of exposure to contemporary, non-persistent pesticides on human sperm quality. A promising new area of reproductive research relates the epigenetic state of spermatozoa to sperm quality. In humans, clinic-based studies indicate that levels of DNA methylation are abnormal in spermatozoa of men with reduced fertility. A significant gap exists in our understanding of the genes that are epigenetically alterd following exposure to non-persistent pesticides. Data documenting the association of exposure to contemporary, non-persistent pesticides on the reproductive health of male farmworkers is needed to inform prevention strategies and public health policy surrounding the use of agricultural pesticides. The goal of this project is to document the association of pesticide exposure with epigenetic changes in spermatogenesis. We will compare 50 male immigrant Latino farmworkers, a group that experiences repeated pesticide exposure, with 50 immigrant Latinos living in urban, non-agricultural communities, without occupational exposure to pesticides. The proposed project will address three specific aims: 1. Methylation binding protein precipitation will be used to enrich imprinted DNA and Next Generation sequencing will be used for genome wide annotation of spermatozoa genes in high- (farmworkers) and low- (non-farmworker) pesticide exposed Latino men. 2. We will correlate biomarkers of non-persistent pesticide exposure (urinary metabolites of organophosphorus pesticides [3,5,6-trichloropyridinol, TCPy/chlorpyrifos], pyrethroid insecticides [3-phenoxybenzoic acid, 3PBA], and herbicides [2,4- dichlorophenoxyacetic acid, 2,4-D]) with the methylation status of spermatozoa genes. 3. Associations among clinically relevant semen parameters (sperm concentration, motility and morphology), urinary pesticide metabolite concentrations and DNA methylation patterns within spermatozoa genes in both groups of men will be determined. This research will combine epidemiology, andrology and epigenomics. The unique longitudinal design of this study will allow us to evaluate cross-sectional differences between high- and low-exposure groups, and changes within populations and individuals across an agricultural season.

 描述（由适用提供）：人口暴露于各种农药。记录了农药暴露对精子质量的有害影响的许多研究已在实验室和动物模型上推断出，从直接人类农药暴露的研究中进行了有限的结果。许多人类研究的重点是使用持续农药，例如DDT（二氯二苯基三氯乙烷），其在发达国家中的使用正在减少。然而，越来越多的研究表明，当代，非持久农药对人类精液参数的微妙影响，包括改善精子浓度和运动性。拉丁裔移民农民工人（其中大多数是男性）是健康的人口，直接且经常接触农药。这些人提供了一个机会，可以检查暴露于当代，非持久农药对人类精子质量的机制和影响。生殖研究的新领域将精子的表观遗传状态与精子质量联系起来。在人类中，基于诊所的研究表明，DNA甲基化水平在生育力降低的男性的精子中是异常的。我们对暴露于非持久农药的基因改变基因的理解存在很大的差距。数据记录需要在男性农民的复制健康方面与当代，非持久农药的接触，以告知预防策略和围绕农业农药使用的公共卫生政策。该项目的目的是记录农药暴露与精子发生的表观遗传变化的关联。我们将比较50名男性移民拉丁裔农场工人，该群体经历了重复的农药暴露，有50名移民拉丁裔生活在城市，非农业社区中，而没有占据农药。拟议的项目将针对三个具体目的：1。甲基化结合蛋白沉淀将用于富集烙印的DNA，下一代测序将用于在高（农场工人）和低（非农业工人）和低（非农业工人）中的精子基因的基因组广泛注释。 2。我们将与非持久性农药暴露的生物标志物（有机磷农药的尿代谢产物[3,5,6-三氯吡啶醇，TCPY/CHORPYPYRIFOS]，甲状腺动物杀虫剂，3-苯氧基苯甲酸，3pba酸酸，3pba，3pba和berbicopher [2,4--dichacicoren [2,4--dichycren， 2,4-d]）具有精子基因的甲基化状态。 3。将确定两组男性中精子基因内的临床相关精液参数（精子浓度，运动和形态），尿农药代谢物浓度和DNA甲基化模式之间的关联。研究将结合流行病学，雄激素和表观基因组学。这项研究的独特纵向设计将使我们能够评估高暴露组和低曝光群体之间的横断面差异，以及在农业季节的人群和个人内部的变化。