PMID- 31272017 OWN - NLM STAT- MEDLINE DCOM- 20200225 LR - 20200225 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 130 DP - 2019 Sep TI - Maternal exposures to persistent organic pollutants are associated with DNA methylation of thyroid hormone-related genes in placenta differently by infant sex. PG - 104956 LID - S0160-4120(19)30559-8 [pii] LID - 10.1016/j.envint.2019.104956 [doi] AB - 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. CI - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Kim, Sujin AU - Kim S AD - Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea; Institute of Environmental Technology, Department of Environmental Engineering, Seoul National University of Science & Technology, Seoul 01811, Republic of Korea. FAU - Cho, Yoon Hee AU - Cho YH AD - Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, University of Montana, Missoula, MT, 59812, USA. FAU - Won, Sungho AU - Won S AD - Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea. FAU - Ku, Ja-Lok AU - Ku JL AD - Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. FAU - Moon, Hyo-Bang AU - Moon HB AD - Department of Marine Science and Convergence Engineering, Hanyang University, Ansan, 15588, Republic of Korea. FAU - Park, Jeongim AU - Park J AD - College of Natural Sciences, Soonchunhyang University, Asan 31538, Republic of Korea. FAU - Choi, Gyuyeon AU - Choi G AD - Department of Obstetrics and Gynecology, College of Medicine, Soonchunhyang University Hospital, Seoul, 04401, Republic of Korea. FAU - Kim, Sungkyoon AU - Kim S AD - Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea. FAU - Choi, Kyungho AU - Choi K AD - Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: kyungho@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190701 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Environmental Pollutants) RN - 0 (Flame Retardants) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Hydrocarbons, Chlorinated) RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (Pesticides) RN - 0 (SLC16A2 protein, human) RN - 0 (Symporters) RN - 0 (Thyroid Hormones) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 1.11.1.- (iodothyronine deiodinase type III) RN - EC 1.11.1.8 (Iodide Peroxidase) SB - IM MH - Adult MH - *DNA Methylation MH - Environmental Pollutants/*blood MH - Epigenesis, Genetic MH - Female MH - Flame Retardants/analysis MH - Halogenated Diphenyl Ethers/blood MH - Humans MH - Hydrocarbons, Chlorinated/blood MH - Infant, Newborn MH - Iodide Peroxidase/*genetics MH - Male MH - *Maternal Exposure MH - Monocarboxylic Acid Transporters/*genetics MH - Pesticides/blood MH - Placenta/*metabolism MH - Polychlorinated Biphenyls/blood MH - Pregnancy MH - *Sex Characteristics MH - Symporters/*genetics MH - Thyroid Hormones/blood OTO - NOTNLM OT - Developmental origins of health and disease (DOHaD) OT - Epigenetics OT - Multipollutant approach OT - Persistent organic pollutant OT - Placenta OT - Thyroid hormone EDAT- 2019/07/05 06:00 MHDA- 2020/02/26 06:00 CRDT- 2019/07/05 06:00 PHST- 2019/02/20 00:00 [received] PHST- 2019/06/21 00:00 [revised] PHST- 2019/06/21 00:00 [accepted] PHST- 2019/07/05 06:00 [pubmed] PHST- 2020/02/26 06:00 [medline] PHST- 2019/07/05 06:00 [entrez] AID - S0160-4120(19)30559-8 [pii] AID - 10.1016/j.envint.2019.104956 [doi] PST - ppublish SO - Environ Int. 2019 Sep;130:104956. doi: 10.1016/j.envint.2019.104956. Epub 2019 Jul 1.