Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A

Toxicol Lett. 2015 Jan 5;232(1):293-300. doi: 10.1016/j.toxlet.2014.10.021. Epub 2014 Oct 17.


Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000μg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000μg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.

Keywords: Bisphenol A; Bisulfite pyrosequencing; DNA methylation; DREAM assay; Developmental programming; Epigenetics.

MeSH terms

  • Age Factors
  • Animals
  • Benzhydryl Compounds / toxicity*
  • Chromatography, High Pressure Liquid
  • Computational Biology
  • CpG Islands
  • DNA Methylation / drug effects*
  • Databases, Genetic
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Environmental Pollutants / toxicity*
  • Female
  • Gestational Age
  • Liver / drug effects*
  • Liver / metabolism
  • Maternal Exposure
  • Mice, Inbred C57BL
  • Phenols / toxicity*
  • Phenotype
  • Polymerase Chain Reaction
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Sex Factors


  • Benzhydryl Compounds
  • Environmental Pollutants
  • Phenols
  • bisphenol A