High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations

Toxicology. 2012 Jun 14;296(1-3):73-82. doi: 10.1016/j.tox.2012.03.007. Epub 2012 Apr 3.


Bisphenol A (BPA) is used as a monomer during the manufacture of polycarbonate plastics and epoxy resins. However, BPA adversely affects reproductive organ growth and development, and it has been proposed that the detrimental effects of BPA could extend to future generations. The present study was conducted to evaluate the transgenerational effects of BPA on hippocampal neurogenesis and neurocognitive function. Pregnant female C57BL/6 mice (F0) were exposed to BPA (0.1-10 mg/kg) from gestation day 6 to 17, and female offspring (F2) from F1 generation mice were prepared. It was found that exposure of F0 mice to BPA at 10 mg/kg decreased the number of newly generated cells in the hippocampi of F2 female mice. Passive avoidance testing revealed that high-doses BPA (1 mg/kg and 10 mg/kg) decreased cross-over latency time in F2 mice, suggesting a BPA-mediated neurocognitive deficit in terms of memory retention. Furthermore, it was found that levels of phospho-ERK, brain-derived neurotrophic factor (BDNF), and phospho-CREB in hippocampi were significantly lower in F2 mice. Interestingly, the effects of BPA on hippocampal neurogenesis were found to be correlated with altered DNA methylation. In particular, high-dose BPA exposure increased DNA methylation of the CREB regulated transcription coactivator 1 (Crtc1) generated in F2 mice. These findings suggest that BPA exposure of pregnant mothers could adversely affect hippocampal neurogenesis and cognitive function in future generations by modulating the ERK and BDNF-CREB signaling cascades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Endocrine Disruptors / toxicity*
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Learning / drug effects
  • Maternal-Fetal Exchange
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis / drug effects*
  • Phenols / toxicity*
  • Pregnancy


  • Benzhydryl Compounds
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Endocrine Disruptors
  • Estrogens, Non-Steroidal
  • Phenols
  • bisphenol A