Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses
Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses
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DOI：
10.1016/j.tox.2012.02.013
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发表时间：
2012-05-16
期刊：
影响因子：
4.5
通讯作者：
Nagao, Tetsuji
中科院分区：
文献类型：
--
作者：
Komada, Munekazu;Asai, Yasuko;Nagao, Tetsuji
双酚A（BPA）是一种内分泌干扰物，广泛用于塑料和树脂的生产。人类在围产期接触这种化学品被认为是对公共健康的一种潜在风险。动物研究表明，出生后暴露于BPA可能会影响胚胎的新皮层发育，加速神经发生，并导致神经元迁移缺陷。然而，详细的表型和发病机制，特别是关于神经干/祖细胞的增殖和分化，尚未阐明。从胚胎第8.5天（E）至第13.5天，经口给予C57 BL/6 J妊娠小鼠200 μ g/kg BPA，并在E14.5时对胎儿进行组织学观察。为了阐明组织学变化，特别是在神经发生、增殖和细胞周期方面，我们使用神经元/神经干细胞的特异性标记物进行组织学分析，并使用胸苷类似物进行细胞周期特异性标记实验。BPA暴露后皮质板增生，神经干/祖细胞数量减少。特别是，母体BPA口服剂量与对端脑背侧脑室下区（SVZ）中的中间祖细胞（IPC，神经祖细胞）的影响有关。BPA可促进SVZ区放射状胶质细胞（RGCs，neural stem cells）和IPC的细胞周期退出，延长IPC的细胞周期长度，抑制其增殖。我们的数据表明，母亲口服BPA与IPC细胞周期的破坏和发育中的新皮层神经发生的影响有关。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Bisphenol A (BPA), an endocrine-disruptor, is widely used in the production of plastics and resins. Human perinatal exposure to this chemical has been proposed to be a potential risk to public health. Animal studies indicate that postnatal exposure to BPA may affect neocortex development in embryos by accelerated neurogenesis and causing neuronal migration defects. The detailed phenotypes and pathogenetic mechanisms, especially with regard to the proliferation and differentiation of neural stem/progenitor cells, however, have not been clarified. C57BL/6J pregnant mice were orally administered BPA at 200 mu g/kg from embryonic day (E) 8.5 to 13.5, and the fetuses were observed histologically at E14.5. To clarify the histological changes, especially in terms of neurogenesis, proliferation and cell cycle, we performed histological analysis using specific markers of neurons/neural stem cells and cell cycle-specific labeling experiments using thymidine-analog substances. Cortical plate was hyperplastic and the number of neural stem/progenitor cells was decreased after the exposure to BPA. In particular, the maternal BPA oral dosing related to the effects on intermediate progenitor cells (IPCs, neural progenitor cells) in the subventricular zone (SVZ) of dorsal telencephalon. Exposure to BPA associated the promotion of the cell cycle exit in radial glial cells (RGCs, neural stem cells) and IPCs, and decreased the proliferation resulting from the prolong cell cycle length of IPCs in the SVZ. Our data show that maternal oral exposure to BPA related to the disruption of the cell cycle in IPCs and the effects of neurogenesis in the developing neocortex. (C) 2012 Elsevier Ireland Ltd. All rights reserved.