Prenatal arsenic speciation and thyroid hormone levels during pregnancy and adolescence

This study aimed to evaluate the association between prenatal exposure to inorganic arsenic (iAs) and maternal and offspring thyroid hormone levels, assessed during pregnancy and at 15 years of age. We also evaluated the role of genetic polymorphisms in the DIO1 and DIO2 genes in this association. The study population comprised pregnant women-offspring pair participants in the INMA project in Spain. Free thyroxine (FT4), total triiodothyronine (TT3) and thyroid-stimulating hormone (TSH) were measured in serum samples collected during the first trimester and at 15 years of age. iAs and its metabolites (DMA, MMA) were measured in urine samples collected during the first trimester. The sum of iAs and its metabolites (SumAs) and the iAs methylation efficiency (%iAs, %DMA, %MMA) were calculated. Covariates were obtained through questionnaires. Two SNPs in the DIO1 (rs2235544) and DIO2 (rs12885300) genes were genotyped in maternal and offspring DNA. The association between maternal As exposure and thyroid hormone levels measured at both time points (n = 981 and n = 330) was evaluated using multivariable linear regression models. Interaction terms were included in the models in order to evaluate effect modification. A lower methylation efficiency of maternal iAs (denoted as higher %MMA) was directly associated with maternal FT4, and maternal SumAs concentrations were directly associated with adolescent TSH levels. Additionally, these associations seemed to be modified by two SNPs in the DIO1 and DIO2 genes. Our results suggest that prenatal exposure to iAs could disrupt thyroid function during both pregnancy and adolescence, and that deiodinase enzymes may play a role.