Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation
Abstract
Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) , perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 μM DES, BPA, TCDD, BDE-47, PCB-153 and 1 μM HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5-25 μM). Adipocyte differentiation was also enhanced by TBT (≥ 10 nM) and BPA (>10 μM) and inhibited by TCDD (≥ 0.1 nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 μM; PCB-153, 3.4 μM and HCB, 1 μM). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.
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The DNA hypomethylating effects of PCB 153 were not observed in the human SK-N-AS neuroblastoma cell line.
“However, the latter finding may be unique to mouse cell lines since the DNA hypomethylating effects of PCB 153 were not observed in the human SK-N-AS neuroblastoma cell line [ 31 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [31]
PCB 153 decreases global DNA methylation levels in the N2A murine neuroblastoma cell line.
“Exposure to the NDL congener PCB 153 decreases DNMT activity in preimplantation mouse blastocytes [ 30 ], and decreases global DNA methylation levels in the N2A murine neuroblastoma cell line [ 31 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [31]
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- Authors
- Bastos Sales, L., Kamstra, J. H., Cenijn, P. H., van Rijt, L. S., Hamers, T., & Legler, J.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Legler, J.
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 27
- Issue
- 6
- Pages
- 1634-1643
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2015008373
- Cited by
- 181
- References
- 48
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 27 · 2023: 7 · 2022: 13 · 2021: 14 · 2020: 14 · 2019: 10 · 2018: 21 · 2017: 18 · 2016: 15 · 2015: 10 · 2014: 23 · 2013: 1
- FWCI
- 11.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- VU Research Portal (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- endocrine disruptors, global DNA methylation, adipogenesis, obesity, epigenetic regulation, bisphenol A, diethylstilbestrol, tributyltin, 2,3,7,8-tetrachlorodibenzo-p-dioxin, BDE-47, hexabromocyclododecane, PCB 153, hexachlorobenzene
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Caprylates, Cell Differentiation, Diethylstilbestrol, Environmental Pollutants, Fluorocarbons, Humans, Hydrocarbons, Brominated, Hydrocarbons, Chlorinated, Phenols, Trialkyltin Compounds, Adipocytes, Alkanesulfonic Acids, DNA Methylation, 3T3-L1 Cells, Cell Line, Tumor, Mice, Endocrine Disruptors, Halogenated Diphenyl Ethers
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