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Gestational exposure to valproic acid upregulates total Stat3 protein expression while downregulating phosphorylated Stat3 in CD‐1 mouse embryos with neural tube defects
Author(s) -
Shafique Sidra,
Winn Louise M.
Publication year - 2020
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1666
Subject(s) - neural tube , stat3 , embryo , downregulation and upregulation , stat protein , biology , phosphorylation , valproic acid , andrology , endocrinology , embryogenesis , in utero , medicine , fetus , pregnancy , microbiology and biotechnology , biochemistry , genetics , epilepsy , neuroscience , gene
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.