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

• 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
• 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' s group; metabolomics; multidisciplinary; neurodevelopment; novel; offspring; persistent organic pollutants; prenatal; prenatal exposure; recruit; reproductive tract; sperm cell; sperm morphology

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.

项目摘要 每种和多氟烷基物质（PFA）是一组人造的持续化学物质， 自1950年代以来广泛应用于商业产品。通常应用的PFA非常持久，并且 人类对PFA的暴露无处不在。动物研究提供了令人信服的数据，即PFA是 内分泌破坏者并可能诱导强烈的发育毒性。越来越多的基于人群的 研究表明，母体和胎儿暴露于PFA与胎儿生长受损有关。一 PFAS研究的领域很大程度上忽略了 PFA关于后代发展的PFA。在实验研究中已经提出了生物合理性 父亲暴露于PFA可能会通过诸如中断的机制影响胎儿发育 精子发生，对精子DNA的损害增加，并改变精子表观遗传学特征。一些父亲 职业和人口因素已与选定的神经发育障碍有关，但是研究 在父亲接触环境毒素上，稀疏。为了解决知识差距，一个多学科 研究人员团队提出了这项新研究，以确定父亲和母亲PFA的影响 胎儿生长和神经发育结果的暴露在588个亲子对中 Inuendo出生队列。 Inuendo是一项多国家的纵向队列研究，来自格陵兰的父母 2002 - 2004年在乌克兰的哈尔基夫（乌克兰）和华沙（波兰）入学。后代随访长达9年 使用跨研究站点的标准数据收集程序旧。环境污染物的面板， 包括六种类型的普通PFA，在母亲和父亲血清样品中均已测量 在怀孕期间收集。此外，父亲的精液质量和精子形态的度量也是 可在588个父子对中提供。我们的具体目的是确定父亲和 母体PFAS暴露与（1）胎儿生长和出生结局相关， （2）5至9岁的儿童行为和运动功能。而且，我们将研究父亲是否 精液质量介导或修改可能对这些儿童健康结果的父亲PFA影响。 该项目的创新包括利用Inuendo队列创造一个独特的机会来研究 PFA暴露对父母双方儿童发育的影响，并使用新颖的统计方法 将精液质量度量纳入分析。这项研究的结果将提高科学知识 父亲PFA的暴露毒性和后代发展。该项目将提供关键数据来评估 与父母双方的环境暴露有关的更广泛的后代健康和利用率 复杂的遗传/表观遗传学和代谢组学方法，以了解暴露症机制。