Maternal exposures to persistent organic pollutants are associated with DNA methylation of thyroid hormone-related genes in placenta differently by infant sex. (September 2019)

• Record Type: Journal Article
• Authors: Kim, Sujin; Cho, Yoon Hee; Won, Sungho; Ku, Ja-Lok; Moon, Hyo-Bang; Park, Jeongim; Choi, Gyuyeon; Kim, Sungkyoon; Choi, Kyungho
• Is Part Of: Environment international. Volume 130(2019)
• Publication Date: 2019-09
• Subjects: BMI body mass index -- CI confidence interval -- DF detection frequency -- DIO3 deiodinase type 3 -- HCH hexachlorocyclohexane -- IQR interquartile range -- LOQ limit of quantification -- MCT8 monocarboxylate transporter 8 -- OCPs organochlorine pesticides -- PBDEs polybrominated diphenyl ethers -- PCBs polychlorinated biphenyls -- POPs persistent organic pollutants -- PCA principal component analysis -- DDE dichlorodiphenyldichloroethylene -- DDT dichlorodiphenyltrichloroethane -- SD standard deviation -- tNonaCHD trans-nonachlordane -- TSH thyroid stimulating hormone -- TTR transthyretin -- T3 triiodothyronine -- T4 thyroxine; Developmental origins of health and disease (DOHaD) -- Epigenetics -- Persistent organic pollutant -- Thyroid hormone -- Multipollutant approach -- Placenta; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2019.104956
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Exposure to persistent organic pollutants (POPs) during pregnancy is associated with a disruption in thyroid hormone balance. The placenta serves as an important environment for fetal development and also regulates thyroid hormone supply to the fetus. However, epigenetic changes of thyroid regulating genes in placenta have rarely been studied. This study was conducted to evaluate the association between several POP concentrations in maternal serum and DNA methylation of thyroid hormone-related genes in the placenta. The placenta samples were collected from 106 Korean mother at delivery, and the promoter methylation of the placental genes was measured by a bisulfite pyrosequencing. The deiodinase type 3 ( DIO3 ), monocarboxylate transporter 8 ( MCT8 ), and transthyretin ( TTR ) genes were selected as the target genes as they play an important role in the regulation of fetal thyroid balance. Because people are exposed to multiple chemicals at the same time, a multiple-POP model using principal component analysis (PCA) was applied to evaluate the association between the multiple POPs exposure and the epigenetic change in placenta. In addition, a single-POP model which includes one chemical each in the statistical model for association was conducted. Based on the single-POP models, serum concentrations of p, p ′-dichlorodiphenyldichloroethylene ( p, p ′-DDE) and brominated diphenyl ether-47 (BDE-47) were significantly associated with an increase in placental DIO3 methylation, but only among female infants. Among male infants, a positive association between serum p, p ′-DDT and MCT8 methylation level was found. According to the multiple-POP models, serum DDTs were positively associated with DIO3 methylation in the placenta of female infants, while a positive association with MCT8 methylation was observed in those of the male infants. Our observation showed that in utero exposure to DDTs may influence the DNA methylation of DIO3 and MCT8 genes in the placenta, in a sexually dimorphic manner. These alterations in placental epigenetic regulation may in part explain the thyroid hormone disruption observed among the newborns or infants followed by in utero exposure to POPs. Highlights: Promoter DNA methylation of placental genes related to thyroid hormone was measured. Some maternal serum POPs were associated with methylation of these placental genes. DNA methylation of DIO3 and MCT8 genes by maternal POP was differed by infant sex.