Valproic acid (VPA), a widely prescribed antiepileptic drug and an effective treatment for psychiatric disorders, is teratogenic causing neural tube defects (NTDs) and other defects in the exposed embryo. Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is activated via tyrosine phosphorylation. Stat3, as well as its active form (pYStat3), is expressed during neural tube closure in murine development. This study investigated the effects of in utero VPA exposure on embryonic Stat3 mRNA and protein expression during the critical period of neural tube closure in CD‐1 mouse embryos. Following the exposure of CD‐1 pregnant mice to the teratogenic dose of 400 mg/kg VPA or saline on gestational day (GD) 9, embryos were harvested at 1, 3, 6, or 24 hr and on GD13. Stat3 mRNA levels remained unchanged at all time points. Total Stat3 protein levels were significantly (p < .05) increased in GD9 embryos at 1 and 6 hr post‐exposure and in GD13 exposed nonexencephalic and exencephalic embryo heads. In contrast, phosphorylated Stat3 levels were significantly (p < .05) downregulated in GD9 embryos at the 3 and 6 hr time points with an overall trend of downregulation in the GD10 and GD13 groups. Total and phosphorylated Stat3 protein levels remained unchanged in nuclear extracts of the exposed nonexencephalic and exencephalic GD13 embryo heads. The reported significant downregulation of phosphorylated Stat3 levels suggests its possible role in VPA‐induced NTDs in mouse embryos.

中文翻译：

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妊娠期暴露于丙戊酸上调总 Stat3 蛋白表达，同时下调具有神经管缺陷的 CD-1 小鼠胚胎中的磷酸化 Stat3

丙戊酸 (VPA) 是一种广泛使用的抗癫痫药物，也是治疗精神疾病的有效药物，它会导致神经管缺陷 (NTD) 和暴露胚胎的其他缺陷。信号转导和转录激活因子 3 (Stat3) 是一种通过酪氨酸磷酸化激活的转录因子。Stat3 及其活性形式 (pYStat3) 在小鼠发育的神经管闭合期间表达。本研究调查了 CD-1 小鼠胚胎神经管闭合关键时期子宫内 VPA 暴露对胚胎 Stat3 mRNA 和蛋白质表达的影响。在妊娠第 9 天 (GD) 将 CD-1 妊娠小鼠暴露于 400 mg/kg VPA 或生理盐水的致畸剂量后，在 1、3、6 或 24 小时和 GD13 收获胚胎。Stat3 mRNA 水平在所有时间点保持不变。总 Stat3 蛋白水平显着 (p  < .05) GD9 胚胎在暴露后 1 小时和 6 小时以及 GD13 暴露的无脑和无脑胚胎头中增加。相比之下， GD9 胚胎在 3 小时和 6 小时时间点磷酸化 Stat3 水平显着下调( p < .05)，GD10 和 GD13 组总体呈下调趋势。在暴露的非脑和外脑 GD13 胚胎头的核提取物中，总和磷酸化的 Stat3 蛋白水平保持不变。报道的磷酸化 Stat3 水平的显着下调表明它可能在 VPA 诱导的小鼠胚胎 NTD 中发挥作用。