Prenatal exposure to POPs mixtures and DNA methylation alterations in multiple tissues at birth

Background/Aim: Prenatal exposure to persistent organic pollutants (POPs) has been linked to adverse health conditions in the offspring. However, little is known about the underlying mechanisms. Growing literature suggests epigenetics may play a role. We aimed to evaluate the associations of prenatal exposure to individual POPs exposure and POP mixtures with global and site-specific DNA methylation (DNAm) changes in cord blood and placenta in the Early Autism Risk Longitudinal Investigation (EARLI) study. Methods: We leveraged existing data on maternal serum POPs collected during early pregnancy and cord blood (n=122) and placenta DNAm (n=80) measured on the Illumina 450K platform at birth. Concentrations of 11 polychlorinated biphenyls (PCBs), 4 polybrominated diphenyls (PBDEs), and 2 persistent pesticides were measured. We examined global DNAm in 5 genomic regions (genome wide, open sea, shelf, shore, and island regions) and site-specific DNAm at 261 loci previously identified to be associated with POPs. Linear regression and quantile g-computation models were performed to evaluate the single pollutant effect and joint effect of POP mixtures on DNAm adjusted for surrogate variables and confounders. Results: Prenatal exposure to PCB 28 was associated with decreased placental DNAm levels at sites located in shelf regions (p=0.04). There was an inverse linear relationship observed between POP mixtures and placental DNAm in open sea regions. POP mixtures were associated with a decrease in methylation levels at 5 sites in cord blood and 14 sites in placenta and an increase in methylation levels at 4 sites in cord blood at nominal level. None of these associations was significant after FDR adjustment. Conclusions. We observed global DNAm changes in placenta associated with prenatal exposure to PCB 28 and POP mixtures. The findings suggest DNAm involvement in response to prenatal environmental exposures in developmentally relevant tissues. Keywords: Persistent organic pollutants, chemical mixtures, DNA methylation, quantile g-computation