Differential methylation of genes in the human placenta associated with bisphenol A exposure

Abstract

Prenatal exposure to bisphenol A (BPA) is associated with numerous adverse health outcomes among offspring. Although DNA methylation is considered one of the underlying causes of these associations, few studies have focused on the association between prenatal BPA exposure and DNA methylation in the human placenta. In this study, we examined the association between prenatal BPA exposure and DNA methylation in the placenta of 146 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study. BPA concentrations in maternal urine samples were measured using high-performance liquid chromatography. Six placenta samples were selected for whole-genome methylation analysis using Infinium Human Methylation 450K Beadchip, followed by pyrosequencing-based methylation analysis of three selected genes in 146 placentas. Among 282 differentially methylated CpGs, representing 208 genes, 127 were hypermethylated, and 155 were hypomethylated in the BPA exposure group. Prenatal BPA exposure was associated with a higher methylation level of HLA-DRB6 in individuals as determined using pyrosequencing, which was consistent with the whole-genome methylation analysis results. Compared with that subjects with low BPA exposure, the methylation level (ln-transformed) of HLA-DRB6 in placentas from those with high BPA exposure increased by 0.29% (95% confidence interval[CI]: 0.02%, 0.56%) at the CpG2 site, and the average methylation level (ln-transformed) of the three CpG sites increased by 0.30% (95%CI: -0.03%, 0.63%). Our findings provide evidence that prenatal BPA exposure might alter DNA methylation levels in the placenta.

Keywords: 450K; Bisphenol A; DNA methylation; Placenta.