Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after exposure to low doses of bisphenol A

Biochem Biophys Res Commun. 2008 Nov 21;376(3):563-7. doi: 10.1016/j.bbrc.2008.09.028. Epub 2008 Sep 17.


Bisphenol A (BPA) is one of endocrine disrupting chemicals, being distributed widely in the environment. We have been studying the low dose effects of BPA on murine forebrain development. Here, we have investigated the genome-wide effect of maternal exposure to BPA on the epigenome in mouse forebrain at E12.5 and at E14.5. We scanned CpG methylation status in 2500 NotI loci, representing 48 (de)methylated unique loci. Methylation status in most of them was primarily developmental stage-dependent. Each of almost all cloned NotI loci was located in a CpG island (CGI) adjacent to 5' end of the transcriptional unit. The mRNA expression of two functionally related genes changed with development as well as the exposure to BPA. In both genes, changes at the transcriptional level correlated well with the changes in NotI methylation status. Taken together, epigenetic alterations in promoter-associated CGIs after exposure to BPA may underlie some effects on brain development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants, Occupational / toxicity*
  • Animals
  • Benzhydryl Compounds
  • CpG Islands / drug effects
  • DNA Methylation / drug effects*
  • Epigenesis, Genetic / drug effects*
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Fetus / drug effects
  • Fetus / metabolism
  • Gene Expression / drug effects
  • Genome
  • Genomics
  • Major Histocompatibility Complex / genetics
  • Maternal Exposure*
  • Mice
  • Mice, Inbred ICR
  • Phenols / toxicity*
  • Promoter Regions, Genetic / drug effects
  • Prosencephalon / drug effects*
  • Prosencephalon / embryology
  • Prosencephalon / metabolism
  • Proteins / genetics
  • Vesicular Transport Proteins


  • Air Pollutants, Occupational
  • Benzhydryl Compounds
  • Estrogens, Non-Steroidal
  • Phenols
  • Proteins
  • Vesicular Transport Proteins
  • Vps52 protein, mouse
  • bisphenol A