{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:40:46Z","timestamp":1785181246146,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MPO115188"],"award-info":[{"award-number":["MPO115188"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u20101 mouse embryos. Following the exposure of CD\u20101 pregnant mice to the teratogenic dose of 400\u2009mg\/kg VPA or saline on gestational day (GD) 9, embryos were harvested at 1, 3, 6, or 24\u2009hr and on GD13. Stat3 mRNA levels remained unchanged at all time points. Total Stat3 protein levels were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) increased in GD9 embryos at 1 and 6 hr post\u2010exposure and in GD13 exposed nonexencephalic and exencephalic embryo heads. In contrast, phosphorylated Stat3 levels were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) 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\u2010induced NTDs in mouse embryos.<\/jats:p>","DOI":"10.1002\/bdr2.1666","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T12:15:07Z","timestamp":1583410507000},"page":"555-568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gestational exposure to valproic acid upregulates total Stat3 protein expression while downregulating phosphorylated Stat3 in CD\u20101 mouse embryos with neural tube defects"],"prefix":"10.1002","volume":"112","author":[{"given":"Sidra","family":"Shafique","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University  Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1088-5538","authenticated-orcid":false,"given":"Louise M.","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University  Kingston Ontario K7L 3N6 Canada"},{"name":"School of Environmental Studies Queen's University  Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23147"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2013.06.015"},{"key":"e_1_2_7_4_1","unstructured":"Bricker J. K.(2016). Examination of the effects of valproic acid exposure or p300 protein inhibition on the balance of apoptosis and proliferation in P19 embryonal carcinoma cells. 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