Effect of perinatal exposure to Bisphenol-A on DNA methylation and histone acetylation in cerebral cortex and hippocampus of postnatal male mice.

Abstract

Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the production of polycarbonate plastics and epoxy resins. Recently we have reported that perinatal BPA exposure impaired spatial memory through upregulation of synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism is a key regulator of memory, we hypothesized that BPA might influence memory through epigenetic regulation of gene expression. Here we provide evidence that perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice. BPA exposure also increased mRNA levels of DNMT1 and DNMT3a in cerebral cortex of 3 and 8 weeks; whereas in hippocampus DNMT1 mRNA increased in 3 weeks but decreased in 8 weeks and DNMT3a showed no change. Further, HDAC2 mRNA and protein increased in cerebral cortex of both ages and in hippocampus it increased in 3 weeks but decreased in 8 weeks. Altogether, our results demonstrate that the perinatal BPA exposure induces epigenetic changes that possibly underlie the enduring effect of BPA on brain function and behavior.