Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size

DNA methylation is one potential mechanism for the effects of gestational exposure to perfluoroalkyl substances (PFASs) on fetal growth. We investigated 180 pregnant women who participated in a cohort study conducted in Tangshan City, Northern China, and determined the concentrations of 11 PFASs and the methylation of two genes re-lated to fetal growth [insulin-like growth factor 2 (IGF2) and nuclear receptor subfamily 3 group C member 1 (NR3C1)] and one surrogate marker for global methylation [long interspersed nuclear element-1 (LINE-1)] in placenta tissue. Multiple linear regression analysis was performed to examine the associations of log transformed PFASs with the DNA methylation and birth size. Weighted quantile sum regression was used to determine the mixture effect of PFASs. After adjusting for potential confounders, perfluorooctane sulfonate (PFOS) was negatively associated with the overall methylation of LINE-1. PFASs mixture was negatively associated with the methylation of all CpG loci of LINE-1 and overall methylation of NR3C1. Perfluorootanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and the PFASs mixture showed negative associations with head circumference. After stratified by newborns' sex, PFOA, PFNA and the PFASs mixture was negatively associated with overall methyl-ation of LINE-1 only in the male subgroup and the methylation of all CpG loci of LINE-1 was negatively associated with ponderal index only in the female subgroup. The interaction of newborns' sex with PFOS and PFOA on overall methylation of IGF2 was statistically significant and so was the interaction of sex with PFOS on overall methylation of LINE-1. These findings suggested that intrauterine exposure to PFASs affected placental DNA methylation and reduced fetal growth, which might be modified by sex.

Automated summary

This study investigated the effects of gestational exposure to PFASs on fetal growth by examining DNA methylation in placenta tissue of pregnant women. The results showed that PFOS was negatively associated with LINE-1 methylation, and the mixture of PFASs was negatively associated with LINE-1 methylation and NR3C1 methylation. PFOA, PFNA, PFDA, and the PFASs mixture were negatively associated with head circumference. Stratified analysis by newborns' sex found that PFOA, PFNA, and the PFASs mixture were negatively associated with LINE-1 methylation in males, and LINE-1 methylation was negatively associated with ponderal index in females. Interactions between newborns' sex and PFOS/PFOA on IGF2 and LINE-1 methylation were statistically significant. These findings suggest that intrauterine exposure to PFASs affects placental DNA methylation and reduces fetal growth, which may be modified by sex.