Kumar Dhiraj, Thakur Mahendra Kumar
Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Institute of Science, Department of Zoology, Banaras Hindu University, India.
J Toxicol Sci. 2017;42(3):281-289. doi: 10.2131/jts.42.281.
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.
双酚A（BPA）是一种具有雌激素活性的内分泌干扰物，主要用于生产聚碳酸酯塑料和环氧树脂。最近我们报道，围产期暴露于双酚A会通过上调雄性小鼠突触蛋白Neurexin1和Neuroligin3来损害空间记忆。由于表观遗传机制是记忆的关键调节因子，我们推测双酚A可能通过基因表达的表观遗传调控来影响记忆。在此，我们提供证据表明，围产期暴露于双酚A会降低出生后3周和8周雄性小鼠大脑皮层和海马体中的5-甲基胞嘧啶DNA（5-mC DNA）水平，但会增加组蛋白H3乙酰化水平。双酚A暴露还会增加3周和8周龄小鼠大脑皮层中DNMT1和DNMT3a的mRNA水平；而在海马体中，DNMT1 mRNA在3周龄时增加，但在8周龄时降低，DNMT3a则无变化。此外，HDAC2的mRNA和蛋白在两个年龄段的大脑皮层中均增加，在海马体中，其在3周龄时增加，但在8周龄时降低。总之，我们的结果表明，围产期暴露于双酚A会诱导表观遗传变化，这可能是双酚A对脑功能和行为产生持久影响的潜在原因。
