Methylparaben and butylparaben alter multipotent mesenchymal stem cell fates towards adipocyte lineage

Toxicol Appl Pharmacol. 2017 Aug 15;329:48-57. doi: 10.1016/j.taap.2017.05.019. Epub 2017 May 17.

Abstract

Paraben esters and their salts are widely used as preservatives in cosmetics, personal care products, pharmaceuticals, and foods. We previously reported that parabens promoted adipocyte differentiation in vitro and increased adiposity but suppressed serum marker of bone formation in vivo. Here, we investigated the effects of parabens (methylparaben and butylparaben) on modulating cell fate of multipotent stem cell line C3H10T1/2. Both parabens modulated adipogenic, osteogenic, and chondrogenic differentiation of C3H10T1/2 cells in vitro. Butylparaben markedly promoted adipogenic differentiation, but suppressed osteogenic and chondrogenic differentiation whereas methylparaben showed similar but less pronounced effects. Moreover, butylparaben, but not methylparaben, was shown to activate peroxisome proliferator-activated receptor (PPAR) γ whereas neither of the paraben was shown to activate glucocorticoid receptor (GR) responsive reporter in C3H10T1/2 cells. The adipogenic effects of butylparaben were significantly attenuated by PPARγ knockdown, but not by GR knockdown. In contrast, paraben's effects on osteoblast differentiation were affected by both knockdowns. Collectively, the results demonstrate opposing effects of parabens on adipogenic and osteoblastogenic/chondrogenic differentiation of multipotent stem cells. In light of the recent findings that parabens are detected in human placenta and milk, our studies provide rationales to study paraben exposure during early development of life in the future.

Keywords: Adiposity; C3H10T1/2; Endocrine disrupting chemicals; Multipotent mesenchymal stem cell; Obesity; Parabens.

Publication types

  • Comparative Study

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipogenesis / drug effects*
  • Animals
  • Cell Line
  • Cell Lineage*
  • Chondrogenesis / drug effects
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Mice, Inbred C3H
  • Osteogenesis / drug effects
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Parabens / toxicity*
  • Phenotype
  • RNA Interference
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Risk Assessment
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection

Substances

  • PPAR gamma
  • Parabens
  • Receptors, Glucocorticoid
  • butylparaben
  • methylparaben