Perinatal PFAS Impact Children's Development: Examining the Roles of Placental Functional Multiomics and Protection by Maternal Exercise

PROJECT SUMMARY Endocrine-disrupting chemicals (EDC), particularly environmentally ubiquitous per- and polyfluoroalkyl substances (PFAS), are thought to contribute to obesity and other chronic diseases. The prenatal period is recognized as a critical window for EDC exposures, including PFAS, that have been associated with alterations in neonatal epigenetic regulation, as well as with children’s growth and development. While prenatal PFAS exposures have been the focus of multiple recent and ongoing studies, the effects of early postnatal PFAS exposure on children’s health and development are largely uncharacterized. This is a critical gap in the field since numerous organ systems are undergoing substantial growth and programming during these early years of life and are likely extremely susceptible to PFAS exposure then. Additionally, while the importance of prenatal PFAS exposures is increasingly recognized, the mechanisms that confer this toxicity to the offspring are still largely unknown. Additional research is required to address these key gaps in the field: (1) whether biological mechanisms can explain some of the relationships between prenatal PFAS exposure and children’s health outcomes, and (2) whether postnatal PFAS exposures also confer risk for children’s health and development. Additionally, given that PFAS contamination is ubiquitous and exposure avoidance is difficult, the identification of lifestyle and behavioral changes that can reduce the PFAS burden or alleviate the risk for adverse effects has the potential for substantial public health impact. Here, we aim to characterize PFAS serum levels at 12 and 24 months of age and relate these to growth and neurodevelopment in a richly phenotyped cohort with 11 points for follow-up through the 24-month visit. Aim 1 will characterize the placental multi-omic responses to PFAS in multi-cohort analyses. We hypothesize that prenatal exposure to PFAS will perturb the activity of a network of epigenomic, micro-RNA, and mRNA features, particularly among genes related to growth and neurodevelopment. Aim 2 will test whether associations between prenatal PFAS exposure and birth outcomes or placental molecular activity are modified by maternal exercise during pregnancy. We hypothesize that the associations between prenatal PFAS and birth outcomes will be attenuated among mothers who exercise; we will also examine whether the associations that are identified in Aim 1 are modified by maternal exercise during pregnancy. Aim 3 will then test the associations between postnatal PFAS levels with children''s growth and development. We hypothesize that postnatal PFAS burden as measured by infant PFAS serum concentrations will significantly affect offspring WLZ-score and fat mass as well as cognitive and language scores. Our transdisciplinary team will produce novel data about mechanisms of disease and dysfunction associated with perinatal PFAS exposure, environmental contaminants suspected to impact children’s health. Additionally, we will leverage a randomized controlled trial to determine whether maternal exercise can mitigate the negative effects of perinatal PFAS exposures. Such results will generate novel avenues to design future interventions to mitigate the PFAS burden for future generations.