Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants
Prenatal exposure to organophosphate esters (OPEs) and polybrominated diphenyl ethers (PBDEs) has been linked to disrupted fetal thyroid hormone (TH), though the underlying mechanisms remain unclear. Based on the S-MBCS cohort, we analyzed OPE metabolite concentrations in maternal urine during early...
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325011856 |
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| author | Min Luan Haijun Zhu Fen Yang Hong Liang Xiuxia Song Longmei Jin Honglei Ji Wei Yuan Qihan Wu Xiujuan Su Maohua Miao |
| author_facet | Min Luan Haijun Zhu Fen Yang Hong Liang Xiuxia Song Longmei Jin Honglei Ji Wei Yuan Qihan Wu Xiujuan Su Maohua Miao |
| author_sort | Min Luan |
| collection | DOAJ |
| description | Prenatal exposure to organophosphate esters (OPEs) and polybrominated diphenyl ethers (PBDEs) has been linked to disrupted fetal thyroid hormone (TH), though the underlying mechanisms remain unclear. Based on the S-MBCS cohort, we analyzed OPE metabolite concentrations in maternal urine during early pregnancy and PBDE levels in cord plasma. Methylation of five TH regulatory genes, namely deiodinase type 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), was quantified in the placenta. We investigated the associations between prenatal exposure to PBDEs and OPEs and DNA methylation of placental TH-related genes, using samples from 240 and 327 mother–newborn pairs, respectively. We further examined sex-specific differences in these associations and assessed whether the observed epigenetic alterations mediated the relationship between exposures and TH disruption. Mediation analyses were conducted in a subset of mother–newborn pairs with available TH measurements in cord plasma. BDE-47 and ΣPBDE showed sex-specific relationships with DIO3 and SLC16A2 methylation, with a significant positive association in females and a non-significant inverse association in males. Both BDE-47 and ΣPBDEs were linked to SLCO1C1 hypermethylation. OPE metabolites were positively associated with DIO3 and TTR methylation, predominantly in females. Mediation analyses suggested that SLCO1C1 hypermethylation mediated 6.5–7.0 % of the association between ΣPBDE exposure and reduced free triiodothyronine. These findings highlight sex-specific epigenetic changes in placental TH-related genes in relation to PBDE and OPE exposure, providing novel insights into fetal thyroid disruption pathways. |
| format | Article |
| id | doaj-art-e7cf260d275b4e3488aa5597fde068e3 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-e7cf260d275b4e3488aa5597fde068e32025-08-20T03:41:31ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130311884010.1016/j.ecoenv.2025.118840Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardantsMin Luan0Haijun Zhu1Fen Yang2Hong Liang3Xiuxia Song4Longmei Jin5Honglei Ji6Wei Yuan7Qihan Wu8Xiujuan Su9Maohua Miao10Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaMinhang Maternal and Child Health Hospital, Shanghai 201100, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, ChinaClinical Research Centre, Shanghai Key Laboratory of Maternal Foetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China; Correspondence to: Clinical Research Centre, Shanghai Key Laboratory of Maternal Foetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No.2699, West Gaoke Road, Shanghai 200120, China.Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China; Correspondence to: Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, 779 Lao Hu Min Road, Shanghai 200237, China.Prenatal exposure to organophosphate esters (OPEs) and polybrominated diphenyl ethers (PBDEs) has been linked to disrupted fetal thyroid hormone (TH), though the underlying mechanisms remain unclear. Based on the S-MBCS cohort, we analyzed OPE metabolite concentrations in maternal urine during early pregnancy and PBDE levels in cord plasma. Methylation of five TH regulatory genes, namely deiodinase type 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), was quantified in the placenta. We investigated the associations between prenatal exposure to PBDEs and OPEs and DNA methylation of placental TH-related genes, using samples from 240 and 327 mother–newborn pairs, respectively. We further examined sex-specific differences in these associations and assessed whether the observed epigenetic alterations mediated the relationship between exposures and TH disruption. Mediation analyses were conducted in a subset of mother–newborn pairs with available TH measurements in cord plasma. BDE-47 and ΣPBDE showed sex-specific relationships with DIO3 and SLC16A2 methylation, with a significant positive association in females and a non-significant inverse association in males. Both BDE-47 and ΣPBDEs were linked to SLCO1C1 hypermethylation. OPE metabolites were positively associated with DIO3 and TTR methylation, predominantly in females. Mediation analyses suggested that SLCO1C1 hypermethylation mediated 6.5–7.0 % of the association between ΣPBDE exposure and reduced free triiodothyronine. These findings highlight sex-specific epigenetic changes in placental TH-related genes in relation to PBDE and OPE exposure, providing novel insights into fetal thyroid disruption pathways.http://www.sciencedirect.com/science/article/pii/S0147651325011856Organophosphate estersPolybrominated diphenyl ethersPlacentaThyroid hormoneDNA methylation |
| spellingShingle | Min Luan Haijun Zhu Fen Yang Hong Liang Xiuxia Song Longmei Jin Honglei Ji Wei Yuan Qihan Wu Xiujuan Su Maohua Miao Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants Ecotoxicology and Environmental Safety Organophosphate esters Polybrominated diphenyl ethers Placenta Thyroid hormone DNA methylation |
| title | Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| title_full | Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| title_fullStr | Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| title_full_unstemmed | Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| title_short | Sex-specific DNA methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| title_sort | sex specific dna methylation changes in placental thyroid hormone regulatory genes following prenatal exposure to flame retardants |
| topic | Organophosphate esters Polybrominated diphenyl ethers Placenta Thyroid hormone DNA methylation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325011856 |
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