PMID- 28011154 OWN - NLM STAT- MEDLINE DCOM- 20170726 LR - 20181202 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 40 DP - 2017 Apr TI - Persistent organic pollutants alter DNA methylation during human adipocyte differentiation. PG - 79-87 LID - S0887-2333(16)30267-3 [pii] LID - 10.1016/j.tiv.2016.12.011 [doi] AB - Ubiquitous persistent organic pollutants (POPs) can accumulate in humans where they might influence differentiation of adipocytes. The aim of this study was to investigate whether DNA methylation is one of the underlying mechanisms by which POPs affect adipocyte differentiation, and to what extent DNA methylation can be related to gene transcription. Adipocyte differentiation was induced in two human cell models with continuous exposure to different POPs throughout differentiation. From the seven tested POPs, perfluorooctanesulfonic acid (PFOS) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreased lipid accumulation, while tributyltin (TBT) increased lipid accumulation. In human mesenchymal stem cells (hMSCs), TCDD and TBT induced opposite gene expression profiles, whereas after PFOS exposure gene expression remained relatively stable. Genome-wide DNA methylation analysis showed that all three POPs affected DNA methylation patterns in adipogenic and other genes, possibly related to the phenotypic outcome, but without concomitant gene expression changes. Differential methylation was predominantly detected in intergenic regions, where the biological relevance of alterations in DNA methylation is unclear. This study demonstrates that POPs, at environmentally relevant levels, are able to induce differential DNA methylation in human differentiating adipocytes. CI - Copyright (c) 2017 Wageningen University. Published by Elsevier Ltd.. All rights reserved. FAU - van den Dungen, Myrthe W AU - van den Dungen MW AD - Division of Human Nutrition, Wageningen University, The Netherlands; Marine Animal Ecology group, Wageningen University, The Netherlands. Electronic address: Myrthe.vandenDungen@wur.nl. FAU - Murk, Albertinka J AU - Murk AJ AD - Marine Animal Ecology group, Wageningen University, The Netherlands. Electronic address: Tinka.Murk@wur.nl. FAU - Kok, Dieuwertje E AU - Kok DE AD - Division of Human Nutrition, Wageningen University, The Netherlands. Electronic address: Dieuwertje.Kok@wur.nl. FAU - Steegenga, Wilma T AU - Steegenga WT AD - Division of Human Nutrition, Wageningen University, The Netherlands. Electronic address: Wilma.Steegenga@wur.nl. LA - eng PT - Journal Article DEP - 20161220 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Alkanesulfonic Acids) RN - 0 (Environmental Pollutants) RN - 0 (Fluorocarbons) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (Trialkyltin Compounds) RN - 4XDX163P3D (tributyltin) RN - 9H2MAI21CL (perfluorooctane sulfonic acid) SB - IM MH - Adipocytes/cytology/*drug effects/metabolism MH - Adipogenesis/genetics MH - Alkanesulfonic Acids/toxicity MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - DNA Methylation/*drug effects MH - Environmental Pollutants/*toxicity MH - Fluorocarbons/toxicity MH - Humans MH - Mesenchymal Stem Cells/cytology/*drug effects/metabolism MH - Polychlorinated Dibenzodioxins/toxicity MH - Transcriptome/drug effects MH - Trialkyltin Compounds/toxicity OTO - NOTNLM OT - Adipocytes OT - DNA methylation OT - Gene expression OT - Human mesenchymal stem cells OT - Infinium 450K BeadChip OT - Persistent organic pollutants (POPs) EDAT- 2016/12/25 06:00 MHDA- 2017/07/27 06:00 CRDT- 2016/12/25 06:00 PHST- 2016/07/02 00:00 [received] PHST- 2016/10/17 00:00 [revised] PHST- 2016/12/18 00:00 [accepted] PHST- 2016/12/25 06:00 [pubmed] PHST- 2017/07/27 06:00 [medline] PHST- 2016/12/25 06:00 [entrez] AID - S0887-2333(16)30267-3 [pii] AID - 10.1016/j.tiv.2016.12.011 [doi] PST - ppublish SO - Toxicol In Vitro. 2017 Apr;40:79-87. doi: 10.1016/j.tiv.2016.12.011. Epub 2016 Dec 20.