A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells

Polina Lizunkova, Elin Engdahl, Gábor Borbély, Chris Gennings, Christian Lindh, Carl Gustaf Bornehag, Joëlle Rüegg

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

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.

Original languageEnglish
Article number2320
JournalInternational Journal of Molecular Sciences
Volume23
Issue number4
DOIs
Publication statusPublished - 2022 Feb

Subject classification (UKÄ)

  • Public Health, Global Health, Social Medicine and Epidemiology
  • Environmental Health and Occupational Health

Keywords

  • Adipogenesis
  • Chemical mixtures
  • DNA methylation
  • EDC
  • Endocrine disrupting chemicals
  • Low birth weight
  • Mesenchymal stem cells

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