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

Lizunkova, Polina ; Engdahl, Elin ; Borbély, Gábor ; Gennings, Chris ; Lindh, Christian LU orcid ; Bornehag, Carl Gustaf LU and Rüegg, Joëlle (2022) In International Journal of Molecular Sciences 23(4).
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipogenesis, Chemical mixtures, DNA methylation, EDC, Endocrine disrupting chemicals, Low birth weight, Mesenchymal stem cells
in
International Journal of Molecular Sciences
volume
23
issue
4
article number
2320
publisher
MDPI AG
external identifiers
  • pmid:35216435
  • scopus:85124884554
ISSN
1661-6596
DOI
10.3390/ijms23042320
language
English
LU publication?
yes
id
a3055cf4-2e5c-47f9-8609-464752d9aa78
date added to LUP
2022-04-13 10:39:53
date last changed
2024-05-22 13:23:21
@article{a3055cf4-2e5c-47f9-8609-464752d9aa78,
  abstract     = {{<p>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.</p>}},
  author       = {{Lizunkova, Polina and Engdahl, Elin and Borbély, Gábor and Gennings, Chris and Lindh, Christian and Bornehag, Carl Gustaf and Rüegg, Joëlle}},
  issn         = {{1661-6596}},
  keywords     = {{Adipogenesis; Chemical mixtures; DNA methylation; EDC; Endocrine disrupting chemicals; Low birth weight; Mesenchymal stem cells}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  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}},
  url          = {{http://dx.doi.org/10.3390/ijms23042320}},
  doi          = {{10.3390/ijms23042320}},
  volume       = {{23}},
  year         = {{2022}},
}