Laboratory of Biochemistry and Immunology, Republic of Korea.
Laboratory of Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Reprod Toxicol. 2020 Aug;95:75-85. doi: 10.1016/j.reprotox.2020.05.010. Epub 2020 May 23.
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.
围产期母亲吸烟与不良新生儿结局有关，如低出生体重和出生缺陷。许多研究表明，香烟烟雾或尼古丁暴露对胎儿神经发育有广泛影响。然而，对于胚胎干细胞 (ESCs) 在分化为神经细胞的过程中持续暴露于香烟烟雾时细胞水平上发生的具体变化，人们还缺乏了解。我们之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。使用化学定义的培养基诱导 mESCs 分化为神经祖细胞 (NPCs) 或神经嵴细胞 (NCCs)，并在神经分化和发育过程中持续暴露于 CSE 或尼古丁。在 NPCs 中观察到多能状态的平衡失调，随后抑制了神经突生长和胶质纤维酸性蛋白 (Gfap) 的表达。这些抑制与涉及 Notch-1 信号通路的蛋白质表达的改变相关。CSE 或尼古丁暴露显著降低了 NCCs 的迁移能力，这与迁移相关蛋白的表达减少有关。总之，我们得出结论，CSE 和尼古丁抑制 mESCs 分化为 NPCs 或 NCCs，并可能破坏神经细胞的功能发育。这些结果表明，围产期吸烟可能会抑制 ESCs 细胞的神经分化和发育，导致新生儿大脑发育异常和行为异常。
