A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells
Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2320 |
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| author | Polina Lizunkova Elin Engdahl Gábor Borbély Chris Gennings Christian Lindh Carl-Gustaf Bornehag Joëlle Rüegg |
| author_facet | Polina Lizunkova Elin Engdahl Gábor Borbély Chris Gennings Christian Lindh Carl-Gustaf Bornehag Joëlle Rüegg |
| author_sort | Polina Lizunkova |
| collection | DOAJ |
| description | Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes. |
| first_indexed | 2024-03-09T21:44:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:44:38Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ff7e884e89ff4521a176a6513ea006722023-11-23T20:23:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234232010.3390/ijms23042320A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem CellsPolina Lizunkova0Elin Engdahl1Gábor Borbély2Chris Gennings3Christian Lindh4Carl-Gustaf Bornehag5Joëlle Rüegg6Department of Organismal Biology, Uppsala University, 75236 Uppsala, SwedenDepartment of Organismal Biology, Uppsala University, 75236 Uppsala, SwedenThe Swedish Toxicology Sciences Research Center (Swetox), 15257 Södertälje, SwedenDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAOccupational and Environmental Medicine, Lund University, 22363 Lund, SwedenDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Organismal Biology, Uppsala University, 75236 Uppsala, SwedenEndocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes.https://www.mdpi.com/1422-0067/23/4/2320Endocrine Disrupting ChemicalsEDCchemical mixturesmesenchymal stem cellsadipogenesisDNA methylation |
| spellingShingle | Polina Lizunkova Elin Engdahl Gábor Borbély Chris Gennings Christian Lindh Carl-Gustaf Bornehag Joëlle Rüegg A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells International Journal of Molecular Sciences Endocrine Disrupting Chemicals EDC chemical mixtures mesenchymal stem cells adipogenesis DNA methylation |
| title | A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells |
| title_full | A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells |
| title_fullStr | A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells |
| title_full_unstemmed | A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells |
| title_short | A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells |
| title_sort | mixture of endocrine disrupting chemicals associated with lower birth weight in children induces adipogenesis and dna methylation changes in human mesenchymal stem cells |
| topic | Endocrine Disrupting Chemicals EDC chemical mixtures mesenchymal stem cells adipogenesis DNA methylation |
| url | https://www.mdpi.com/1422-0067/23/4/2320 |
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