Nuclear factor kappa B (NF-κB) is a heterodimer of protein subunits p65 and p50, that regulates the expression of a large number of genes related to cell growth and proliferation. The p65 subunit is activated after phosphorylation by Pim-1, while the p50 subunit is the cleaved product of its precursor molecule p105. Valproic acid (VPA), an antiepileptic drug, is a known teratogen and its exposure during pregnancy is associated with 1–2% of neural tube defects in the offspring. The current study aimed at investigating the effects of in utero VPA exposure on the key components of the NF-κB signaling pathway including p65, p50, and Pim-1 in CD-1 mouse embryos during the critical period of neural tube closure. Here we report that p65, Pim-1 and p105/p50 mRNA were significantly (p < 0.05) downregulated at 1 and 3 h following in utero exposure to a teratogenic dose (400 mg/kg) of VPA in gestational day (GD)9 exposed embryos. At GD13 heads of control, non-exencephalic and exencephalic embryos were used for analysis and we found significant upregulation of p65 protein expression in non-exencephalic GD13 heads while p50 protein levels were significantly downregulated in both non-exencephalic and exencephalic groups. On the other hand, p65 and p50 protein levels remained unchanged in the nuclear extracts of the VPA-exposed non-exencephalic and exencephalic GD13 embryo heads. The reported results suggest that VPA exposure perturbates p65, p105/p50, Pim-1 transcript and p65/p50 protein levels in mouse embryos.

核因子 kappa B (NF-κB) 是蛋白质亚基 p65 和 p50 的异二聚体，可调节与细胞生长和增殖相关的大量基因的表达。p65 亚基在被 Pim-1 磷酸化后被激活，而 p50 亚基是其前体分子 p105 的裂解产物。丙戊酸 (VPA) 是一种抗癫痫药，是一种已知的致畸剂，妊娠期间暴露于其与 1-2% 的后代神经管缺陷有关。目前的研究旨在调查子宫内VPA 暴露对神经管闭合关键时期 CD-1 小鼠胚胎中 NF-κB 信号通路的关键成分（包括 p65、p50 和 Pim-1）的影响。在这里我们报告 p65、Pim-1 和 p105/p50 mRNA 显着（p < 0.05)在妊娠第 9 天 (GD) 暴露的胚胎在子宫内暴露于致畸剂量 (400 mg/kg) 的 VPA后 1 和 3 小时下调。在对照的 GD13 头部，使用非外脑和外脑胚胎进行分析，我们发现非外脑 GD13 头中 p65 蛋白表达显着上调，而 p50 蛋白水平在非外脑和外脑组中均显着下调。另一方面，在暴露于 VPA 的非外脑和外脑 GD13 胚胎头的核提取物中，p65 和 p50 蛋白水平保持不变。报告的结果表明，VPA 暴露会扰乱小鼠胚胎中的 p65、p105/p50、Pim-1 转录物和 p65/p50 蛋白水平。