In Vivo Investigation of Perinatal PFAS Exposure through Drinking Water on Birth Outcomes and Neurodevelopment in Offspring

Abstract

Pittsboro, North Carolina, has been burdened by exceptionally high concentration of per- and polyfluoroalkyl substances (PFAS) contamination in drinking water. Our previous study reported that perinatal exposure to a PFAS mixture mimicking the PFAS levels in Pittsboro, NC drinking water led to gestational hypertension and lower fetal weights in rabbits. However, there has been significant gaps in literature uncovering the toxicity and biological processes and physiological mechanisms affected by this PFAS mixture, which hindered researchers and policy makers articulate the harm of PFAS chemicals to communities like Pittsboro, NC. This study, therefore, aims to supply evidence that helps establish a causal relationship between in utero exposure to this PFAS mixture and birth outcomes, focusing on the neurodevelopment of offspring in rats. Various neurobehavioral tests, molecular, and pathological examinations have been accomplished to uncover physiological alterations associated with maternal PFAS mixture exposure and underlying mechanisms. Our research discovered that maternal PFAS exposure led to a significant delay in pup locomotor development in a sex-specific manner and reduced brain volume in postnatal day 1 (PND 1) pups. Transcriptome analysis identified 564 differentially expressed genes (DEGs) in cerebellum samples collected from the low-dose PFAS group. The DEGs are enriched in mitochondrial and metabolic pathways or pathogenetic ontologies suggest abnormal neurodevelopment including locomotor signals.