Maternal smoking during the perinatal period is linked to adverse neonatal outcomes such as low birth weight and birth defects. Numerous studies have shown that cigarette smoke or nicotine exposure has a widespread effect on fetal nerve development. However, there exists a lack of understanding of what specific changes occur at the cellular level on persistent exposure to cigarette smoke during the differentiation of embryonic stem cells (ESCs) into neural cells. We previously investigated the effects of cigarette smoke extract (CSE) and its major component, nicotine, on the neural differentiation of mouse embryonic stem cells (mESCs). Differentiation of mESCs into neural progenitor cells (NPCs) or neural crest cells (NCCs) was induced with chemically defined media, and the cells were continuously exposed to CSE or nicotine during neural differentiation and development. Disturbed balance of the pluripotency state was observed in the NPCs, with consequent inhibition of neurite outgrowth and glial fibrillary acidic protein (Gfap) expression. These inhibitions correlated with the altered expression of proteins involved in the Notch-1 signaling pathways. The migration ability of NCCs was significantly decreased by CSE or nicotine exposure, which was associated with reduced protein expression of migration-related proteins. Taken together, we concluded that CSE and nicotine inhibit differentiation of mESCs into NPCs or NCCs, and may disrupt functional development of neural cells. These results imply that cigarette smoking during the perinatal period potentially inhibits neural differentiation and development of ESCs cells, leading to neonatal abnormal brain development and behavioral abnormalities.

围产期的孕妇吸烟与不良的新生儿结局有关，例如低出生体重和出生缺陷。大量研究表明，香烟烟雾或尼古丁暴露对胎儿神经发育有广泛影响。但是，对于在胚胎干细胞（ESC）分化为神经细胞过程中持续接触香烟烟雾，在细胞水平上会发生什么具体变化尚缺乏了解。我们以前研究了香烟烟雾提取物（CSE）及其主要成分尼古丁对小鼠胚胎干细胞（mESCs）神经分化的影响。化学定义的培养基可诱导mESC分化为神经祖细胞（NPC）或神经rest细胞（NCC），在神经分化和发育过程中，细胞连续暴露于CSE或尼古丁。在NPC中观察到多能状态的平衡紊乱，从而抑制了神经突的生长和神经胶质纤维酸性蛋白（Gfap）的表达。这些抑制作用与Notch-1信号通路中涉及的蛋白质表达的改变有关。NSE的迁移能力因CSE或尼古丁暴露而显着降低，这与迁移相关蛋白的蛋白表达降低有关。两者合计，我们得出结论，CSE和尼古丁会抑制mESC分化为NPC或NCC，并可能破坏神经细胞的功能发育。