Paternal and Maternal Perfluoroalkyl Substance Exposure and Offspring health

项目摘要 全氟烷基和多氟烷基物质（PFAS）是一组人造持久性化学品， 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， 人类暴露于PFAS是普遍存在。动物研究提供了令人信服的数据，PFAS是 内分泌干扰物，并可诱导强烈的发育毒性。越来越多的人口 研究表明母体和胎儿暴露于PFAS与胎儿生长受损有关。一 PFAS研究的一个领域在很大程度上被忽视了父亲暴露于 PFAS对后代发育的影响。生物相容性在实验研究中已经提出， 父亲暴露于PFAS可能会影响胎儿发育的机制，如破坏 精子发生、增加精子DNA损伤和改变精子表观遗传特征。一些父亲 职业和人口统计学因素与选定的神经发育障碍有关， 关于父亲接触环境毒素的证据很少为了解决知识差距问题， 一组研究人员提出了这项新的研究，以确定父亲和母亲PFAS的影响， 在588对参加研究的父母-孩子对中， INUENDO出生队列。INUENDO是一项针对格陵兰父母的多国纵向队列研究， 哈尔科夫（乌克兰）和华沙（波兰）在2002-2004年期间入学。对后代进行了长达9年的随访 使用跨研究中心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，在母亲和父亲的血清样品中进行了测量 在怀孕期间收集。此外，还对父亲精液质量和精子形态进行了测量。 在588对父子中可用。我们的具体目标是确定父亲和 母体PFAS暴露单独和/或联合与（1）胎儿生长和出生结果相关， （2）5 ~ 9岁儿童的行为和运动功能。此外，我们还将研究 精液质量介导或改变可能的父亲PFAS对这些儿童健康结果的影响。 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 PFAS暴露对父母双方儿童发育的影响，并使用新的统计方法， 在分析中纳入精液质量指标。这项研究的结果将促进科学知识， 父亲PFAS暴露毒性和后代发育。该项目将提供关键数据，以评估 更广泛的后代健康与环境暴露在父母双方，和利用 复杂的遗传/表观遗传和代谢组学方法来理解疾病机制。

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.