Maternal per- and polyfluoroalkyl substance concentrations and placental DNA methylation of thyroid hormone-related genes.

Studies suggested that per- and polyfluoroalkyl substances (PFAS) may have adverse effects on fetus by altering placental DNA methylation. In the study, we explored associations of maternal PFAS concentrations with placental DNA methylation of thyroid hormone (TH)-related genes and the potential mediating role of DNA methylation levels in PFAS-fetal TH associations. We measured PFAS concentrations in maternal plasma in early pregnancy and levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in cord plasma. We assessed DNA methylation in 345 placental samples for five TH-related genes, i.e., iodothyronine deiodinase 3 (DIO3), solute carrier family 16 member 2 (SLC16A2), solute carrier organic anion transporter family member 1C1 (SLCO1C1), thyrotropin-releasing hormone (TRH), and transthyretin (TTR). We found the associations of PFDA with increased SLC16A2 methylation, PFOA with decreased SLCO1C1 methylation, PFOS with increased TRH methylation, and PFDoA with decreased TRH methylation, and these associations showed sex-specific patterns. Mediation analyses suggested placental SLCO1C1 and SLC16A2 methylation as potential mediators in the associations of PFOA with FT3 and PFUdA with TT4, respectively. These findings provided evidence for associations between prenatal PFAS exposure and epigenetic changes in placental TH-related genes.