Epigenetic Implications of Chronic PFOA Exposure: A Shanghai Birth Cohort Study

Abstract

PFAS are widespread and persistent environmental toxins of growing concern in China. PFOA was the primary compound found in blood samples from the Shanghai Birth Cohort, a large scale prospective longitudinal project emphasizing the Developmental Origin of Health and Diseases (DOHaD) hypothesis, which states that perinatal and early life exposures to toxins largely impact determine lifetime health outcomes. The present study aims to determine if aberrant placental DNA methylation is present in subjects highly exposed to PFOA. Subjects (n = 10, 5 with high PFOA concentrations in their blood and 5 with low concentrations) contributed a placental tissue sample, from which DNA was extracted. This DNA underwent Guide Positioning Sequencing, a recently developed whole-genome DNA methylation profiling method acclaimed for having more definitive mapping than traditional methods. Differential methylation regions (DMRs) were defined as 1,000 base pair sections with average methylation varying ≥10% between the low and high PFOA groups. Most DMRs (64%) were mapped to distal intergenic regions, and somatic chromosomes 1, 8, 13, and 22, were most impacted. The biological processes with highest number of differentially methylated contributory genes were related to sensory perception, smell, axon development, and synapse organization. The number of differentially methylated genes annotated to each biological process ranged from 8 to 159 (median = 48.5, mean = 53). Many biological processes and genes experiencing differential methylation are instrumental in neurological functioning, so going forward, it is important for Shanghai Birth Cohort facilitators to monitor the neurodevelopment of offspring born to highly exposed mothers. Additional studies with larger sample sizes are needed to further elucidate how placental DNA methylation mediates the impact of PFOA on pregnancy outcomes.