孕产妇的肥胖会诱导激活蛋白1介导的炎症反应,从而损害胚胎神经发生
Li-Wei Chen1, Md Nazmul Hossain1, Yao Gao1
1Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, Washington, USA.
The Journal of physiology
|March 13, 2026
概括
孕产妇肥胖 (MO) 通过创造有利于炎症的环境来抑制早期胚胎神经发生. 这项研究揭示了MO损害胎儿大脑发育,并确定了将炎症与减少神经生成联系起来的分子机制.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 孕产妇肥胖 (MO) 是一个全球性的健康问题,与不良后代神经发育结果有关.
- 摩托罗拉对胎儿大脑发育的影响的精确分子机制在很大程度上是未知的.
研究的目的:
- 研究由母亲肥胖引起的胎儿神经发育障碍背后的分子机制.
- 为了确定暴露在孕产妇肥胖的发育大脑中的特定细胞和分子变化.
主要方法:
- 在怀孕期间使用一种高脂肪饮食 (HFD) 诱导的孕产妇肥胖的小鼠模型.
- 在胚胎样本上使用单细胞RNA测序 (scRNA-seq) 和单细胞ATAC测序 (scATAC-seq).
- 进行了体外实验,用瘤亡因子-α (TNF-α) 治疗神经细胞.
主要成果:
- scRNA-seq在肥胖母亲的胚胎中发现了神经元和神经元原始体的比例降低.
- 观察到关键的神经发生转录因子 (Neurod1,Neurog2,Ascl1) 的下调和炎症标志物 (TNF-α,Cxcl2) 的上调.
- scATAC-seq显示MO胚胎中的炎症基因位点 (Tnf,Cd68) 的染色质可访问性和AP-1转录因子活性增加.
- 在体外TNF-α治疗抑制了神经性基因表达,证实了炎症和神经发生障碍之间的直接联系.
结论:
- 孕产妇的肥胖会形成一种促炎性子宫内环境,从而显著扰乱胎儿的神经发生.
- 这项研究阐明了分子通路,包括AP-1介导的炎症基因激活,导致肥胖母亲后代的神经发育缺陷.
- 这些发现为与母亲肥胖相关的神经发育障碍的病因提供了关键的见解.
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