The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis

Environ Health Perspect. 2005 Jun;113(6):675-9. doi: 10.1289/ehp.7633.


Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 microg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.

Publication types

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

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Dendritic Spines / drug effects*
  • Dendritic Spines / ultrastructure
  • Estradiol
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Ovariectomy
  • Phenols / toxicity*
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / drug effects*
  • Synapses / ultrastructure


  • Benzhydryl Compounds
  • Estrogens, Non-Steroidal
  • Phenols
  • Estradiol
  • bisphenol A