Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-D-aspartate receptors of hippocampus in male offspring mice

Horm Behav. 2010 Jul;58(2):326-33. doi: 10.1016/j.yhbeh.2010.02.012. Epub 2010 Mar 3.


Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24h after received footshock was obviously reduced by exposure to BPA at 5 and 50mg/kg/d (P<0.01) in the PND 21 offspring or at 50mg/kg/d in the PND 56 offspring (P<0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERbeta) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERbeta in hippocampus during postnatal development stage may be involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Animals, Newborn
  • Benzhydryl Compounds
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Estrogen Receptor beta / metabolism
  • Estrogens, Non-Steroidal / administration & dosage
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / metabolism
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / metabolism
  • Mice
  • Mice, Inbred ICR
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Random Allocation
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Benzhydryl Compounds
  • Estrogen Receptor beta
  • Estrogens, Non-Steroidal
  • Phenols
  • Receptors, N-Methyl-D-Aspartate
  • bisphenol A