Perinatal exposure to low-dose bisphenol A disrupts learning/memory and DNA methylation of estrogen receptor alpha in the hippocampus

摘要

Developmental exposure to bisphenol A (BPA) has been indicated to pose long-lasting effects on brain development and behaviors in adulthood. Previous studies have also shown that BPA may disrupt the epigenetic programming of genes in the brain. Here, we focused on investigating the effects of perinatal exposure to low-dose BPA on learning/memory function and emotional regulation, as well as the associated molecular events. Pregnant Sprague-Dawley (SD) rats were treated with control corn oil or BPA (40 μg kg^–1 per day) throughout gestation and lactation. Morris water maze (MWM) and elevated plus maze (EPM) were used to evaluate learning/memory and anxiety-like behaviors at postnatal day (PND) 60 and 85 respectively. The expression level of mRNA for estrogen receptors (ER), ERα and ERβ, in the hippocampus and the serum corticosterone level were determined, as well as the DNA methylation status of the ERα gene promoter. Perinatal exposure to BPA prolonged the escape latency independent of gender, and decreased the percentage of time spent in the target quadrant when examined in the MWM task. While no substantial alteration was observed in the EPM test, the serum corticosterone level was altered in a gender-specific manner. BPA also decreased the expression of mRNA for ERα in the hippocampus, along with elevated DNA methylation of the ERα gene promoter. These results suggest that perinatal exposure to BPA impairs learning/memory function and elevated DNA methylation of the ERα gene in the hippocampus may be involved.