Department of Pathology & Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Neuropathology. 2012 Aug;32(4):447-57. doi: 10.1111/j.1440-1789.2011.01287.x. Epub 2012 Jan 12.
Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in various industries and the field of dentistry. The consequent increase in BPA exposure among humans has led us to some concerns regarding the potential deleterious effects on reproduction and brain development. The emphasis of this review is on the effects of prenatal and lactational exposure to low doses of BPA on brain development in mice. We demonstrated that prenatal exposure to BPA affected fetal murine neocortical development by accelerating neuronal differentiation/migration during the early embryonic stage, which was associated with up- and down-regulation of the genes critical for brain development, including the basic helix-loop-helix transcription factors. In the adult mice brains, both abnormal neocortical architecture and abnormal corticothalamic projections persisted in the group exposed to the BPA. Functionally, BPA exposure disturbed murine behavior, accompanied with a disrupted neurotransmitter system, including monoamines, in the postnatal development period and in adult mice. We also demonstrated that epigenetic alterations in promoter-associated CpG islands might underlie some of the effects on brain development after exposure to BPA.
双酚 A（BPA）是一种内分泌干扰化学物质，广泛应用于各个行业和牙科领域。由于人类接触 BPA 的情况不断增加，人们开始担忧其对生殖和大脑发育可能产生的有害影响。本篇综述的重点是围孕期和哺乳期低剂量 BPA 暴露对小鼠大脑发育的影响。我们发现，BPA 暴露会通过加速胚胎早期的神经元分化/迁移，影响胎儿鼠新皮质的发育，这与大脑发育相关的关键基因的上调和下调有关，包括碱性螺旋-环-螺旋转录因子。在成年小鼠的大脑中，暴露于 BPA 的小鼠的新皮质结构仍然异常，皮质-丘脑投射也异常。功能上，BPA 暴露会干扰小鼠的行为，伴随着神经递质系统的破坏，包括在出生后的发育阶段和成年小鼠中的单胺类神经递质。我们还表明，暴露于 BPA 后，启动子相关 CpG 岛的表观遗传改变可能是对大脑发育产生影响的部分原因。
