Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

Biochem Biophys Res Commun. 2012 Jan 13;417(2):747-52. doi: 10.1016/j.bbrc.2011.12.028. Epub 2011 Dec 16.

Abstract

Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects*
  • Animals
  • Benzhydryl Compounds
  • Cell Line
  • Diethylhexyl Phthalate / pharmacology*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects*
  • Endocrine Disruptors / pharmacology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mice
  • Phenols / pharmacology*
  • Trialkyltin Compounds / pharmacology*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Trialkyltin Compounds
  • tributyltin
  • Diethylhexyl Phthalate
  • bisphenol A