Paternal and Maternal Perfluoroalkyl Substance Exposure and Offspring health

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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.