Time- and dose-dependent effects of ethanol on mouse embryonic stem cells

Reprod Toxicol. 2015 Nov:57:157-64. doi: 10.1016/j.reprotox.2015.06.044. Epub 2015 Jun 11.

Abstract

Ethanol is a common solvent used with mouse embryonic stem (mES) cells in protocols to test chemicals for evidence of developmental toxicity. In this study, dose-response relationships for ethanol toxicity in mES cells were examined. For cells maintained in an undifferentiated state, ethanol significantly reduced viable cell numbers with estimated half maximal inhibitory concentrations of 1.5% and 0.8% ethanol after 24 and 48h, respectively, observations which correlated with significantly increased expression of apoptotic markers. For cells cultured to induce cardiomyocyte formation, up to 0.5% ethanol during the first two days failed to alter the outcome of differentiation, whereas 0.3% ethanol for 11 days significantly reduced the fraction of cultures containing contracting areas, an observation that correlated with significantly reduced cell numbers. These results suggest that ethanol is not an inert solvent at concentrations that might be used for developmental toxicity testing.

Keywords: Apoptosis; Cardiomyocyte; Cytotoxicity; Differentiation; Embryonic stem cell; Ethanol.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Ethanol / toxicity*
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects*
  • Myocytes, Cardiac / cytology
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Time Factors

Substances

  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Ethanol