Paternal and Maternal Perfluoroalkyl Substance Exposure and Offspring health

父亲和母亲全氟烷基物质暴露与后代健康

基本信息

批准号：
10287991
负责人：
Zeyan Liew
金额：
$ 8.38万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-21 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10287991
关键词：
9 year old Address Adverse effects Affect Age Animals Area Behavior Behavioral Biological Birth Birth Weight Birth length Chemicals Child Child Development Child Health Childbirth Childhood Chlorinated Hydrocarbons Complex Country DNA DNA Damage Data Data Collection Data Sources Data Store Demographic Factors Development Developmental Coordination Disorders Diet Disease Endocrine Disruptors Enrollment Environment Environmental Exposure Environmental Pollution Epigenetic Process Exposure to Fathers Fertility Study Fetal Development Fetal Growth Fetal Growth Retardation Fetus General Population Genetic Gestational Age Goals Greenland Growth and Development function Head circumference Health Human Individual Industrial Product Joints Knowledge Lead Link Longitudinal cohort Longitudinal cohort study Maternal Exposure Measures Mediating Mediation Modernization Molecular Morphology Mothers Motor Neurodevelopmental Disorder Newborn Infant Occupational Outcome Outcome Measure Parents Paternal Exposure Pathway interactions Poland Poly-fluoroalkyl substances Polychlorinated Biphenyls Population Study Pregnancy Procedures Public Health Questionnaires Reporting Research Research Personnel Role Sampling Scientific Advances and Accomplishments Second Pregnancy Trimester Seminal Seminal fluid Serum Site Spermiogenesis Third Pregnancy Trimester Toxic Environmental Substances Toxic effect Toxicology Ukraine biobank cell motility cohort critical developmental period data standards developmental toxicity epidemiology study experience experimental study exposed human population follow-up innovation men&apos s group metabolomics multidisciplinary neurodevelopment novel offspring persistent organic pollutants prenatal prenatal exposure recruit reproductive tract sperm cell sperm morphology

项目摘要

Project Summary Per- and poly-fluoroalkyl substances (PFAS) are a group of man-made persistent chemicals, which have been widely applied in commercial products since the 1950s. Commonly applied PFAS are extremely persistent and human exposure to PFAS are ubiquitous. Animal studies have provided compelling data that PFAS are endocrine disruptors and can induce strong developmental toxicity. An increasing number of population-based studies have indicated maternal and fetal exposure to PFAS was associated with impaired fetal growth. One area of PFAS research that has been largely overlooked is the possible adverse effect of paternal exposure to PFAS on offspring development. Biological plausibility has been suggested in experimental studies that paternal exposure to PFAS could affect fetal development via mechanisms such as the disruption of spermiogenesis, increasing damage to sperm DNA, and modifying sperm epigenetic profiles. Some paternal occupational and demographic factors have been linked to selected neurodevelopmental disorders, but studies on paternal exposure to environmental toxins are sparse. To address the knowledge gap, a multidisciplinary team of investigators propose this novel study to determine the impact of paternal and maternal PFAS exposure on fetal growth and neurodevelopmental outcomes among 588 parent-child pairs enrolled in the INUENDO birth cohort. INUENDO is a multi-country longitudinal cohort study of parents from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) enrolled during 2002-2004. The offspring were followed up to 9 years old using standardized data collection procedures across study sites. A panel of environmental contaminants, including six types of common PFAS, have been measured in both maternal and paternal serum samples collected during pregnancy. In addition, measures of paternal seminal quality and sperm morphology are also available in the 588 father-child pairs. Our specific aims are to determine the extent to which paternal and maternal PFAS exposures are individually and/or jointly associated with (1) fetal growth and birth outcomes, and (2) child behavioral and motor functions at ages 5 to 9 years. Moreover, we will study whether paternal semen quality mediates or modifies the possible paternal PFAS effects on these child health outcomes. Innovations of this project include leveraging the INUENDO cohort to create a unique opportunity to study the effects of PFAS exposure on child development in both parents, and to use novel statistical approaches to incorporate semen quality measures in analyses. Findings from this study will advance scientific knowledge of paternal PFAS exposure toxicity and offspring development. This project will provide critical data to evaluate a broader range of offspring health associated with environmental exposures in both parents, and the utilization of complex genetic/epigenetic and metabolomics approaches to understand exposure-disease mechanisms.

项目概要全氟烷基物质和多氟烷基物质 (PFAS) 是一组人造持久性化学品，已被自20世纪50年代以来广泛应用于商业产品。常用的 PFAS 具有极强的持久性和人类接触 PFAS 的现象无处不在。动物研究提供了令人信服的数据，表明 PFAS 内分泌干扰物，可引起强烈的发育毒性。以人口为基础的数量不断增加研究表明，母体和胎儿接触 PFAS 与胎儿生长受损有关。一 PFAS 研究中被广泛忽视的领域是父亲接触 PFAS 可能产生的不利影响 PFAS 对后代发育的影响。实验研究表明生物学的合理性父亲接触 PFAS 可能会通过破坏胎儿发育等机制影响胎儿发育。精子发生、增加精子 DNA 损伤以及改变精子表观遗传特征。一些父辈的职业和人口因素与某些神经发育障碍有关，但研究关于父亲接触环境毒素的情况很少。为了解决知识差距，需要多学科研究小组提出这项新颖的研究，以确定父亲和母亲 PFAS 的影响参与该研究的 588 对亲子对胎儿生长和神经发育结果的暴露 INUENDO 出生队列。 INUENDO 是一项针对格陵兰岛父母的多国纵向队列研究，哈尔科夫（乌克兰）和华沙（波兰）于 2002 年至 2004 年期间入学。后代被随访长达9年旧使用跨研究地点的标准化数据收集程序。一组环境污染物，包括六种常见的 PFAS，已在母体和父体血清样本中检测到怀孕期间收集的。此外，还对父亲精液质量和精子形态进行测量共有588对父子对。我们的具体目标是确定父亲和母亲在多大程度上母亲接触 PFAS 与 (1) 胎儿生长和出生结果单独和/或共同相关， (2) 5 至 9 岁儿童的行为和运动功能。此外，我们还将研究父亲是否精液质量调节或改变父亲 PFAS 对这些儿童健康结果可能产生的影响。该项目的创新包括利用 INUENDO 群体创造一个独特的机会来研究 PFAS 暴露对父母双方儿童发育的影响，并使用新的统计方法来将精液质量测量纳入分析中。这项研究的结果将促进科学知识的发展父亲 PFAS 暴露毒性和后代发育。该项目将提供关键数据来评估与父母双方环境暴露相关的更广泛的后代健康以及利用复杂的遗传/表观遗传和代谢组学方法来了解暴露疾病机制。