Prenatal Perfluoroalkyl Substance Exposure in Association with Global Histone Post-Translational Methylation in 2-Year-Old Children

Abstract

Perfluoroalkyl substances (PFASs) have elimination half-lives in years in humans and are persistent in the environment. PFASs can cross the placenta and impact fetal development. Exposure to PFASs may lead to adverse effects through epigenetic mechanisms. This study aimed to investigate whether prenatal exposure to perfluorooctyl sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) was associated with global histone methylation level changes among the 130 2-year-old children followed-up in a birth cohort study in Taiwan. PFOS, PFOA, PFNA, and PFUA were measured by UHPLC/MS/MS in cord blood. Global histone methylation levels were measured from the blood leukocytes of 2-year-old children by Western blotting. Multivariable regression analyses were applied to adjust for potential confounding effects. Among the 2-year-old children, an IQR increase in the natural log-transformed PFUA exposure was associated with an increased H3K4me3 level by 2.76-fold (95%CI = (0.79, 4.73), p = 0.007). PFOA and PFNA exposures was associated with a decreased H3K27me3 level by 2.35-fold (95%CI = (-4.29, -0.41), p = 0.01) and 2.01-fold (95%CI = (-4.00, -0.03), p = 0.04), respectively. Our findings suggest that prenatal PFAS exposure affected histone post-translational modifications.

Keywords: birth cohort study; epigenetics; histone post-translational modifications; perfluoroalkyl substances; prenatal exposure.