WEI-HSUAN YUYI-LWUN HOPo-Tsang HuangShian-Ling ChuHuai-Jen TsaiHORNG-HUEI LIOU2020-02-062020-02-0620161530-7905https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953365625&doi=10.1007%2fs12012-015-9316-0&partnerID=40&md5=1efff9099fc3c40933e62fb641e77a4ahttps://scholars.lib.ntu.edu.tw/handle/123456789/454694https://pubmed.ncbi.nlm.nih.gov/25724324/The effects of the phosphorylation state of the glycogen synthase kinase 3β involved in the cardiac myocytes (jelly-like cells) epithelial-mesenchymal transition-associated migration during heart-valve formation were examined through the valproic acid-induced cardiac teratogenicity of transgenic line A34 of Tg in a the Brachydanio rerio embryo model. Valproic acid is an effective anti-epileptic drug; however, when taken by pregnant women to treat epilepsy, it can produce cardiac developmental defects in fetuses. In this study, the role of glycogen synthase kinase 3β in valproic acid-induced cardiac teratogenicity was investigated. Transgenic line A34 of zebrafish embryos was used at 3 days postfertilization. The results show that 78% (18/23) of the embryos treated with 0.10 mM valproic acid (group A) had incomplete chamber formation with normal looping and 22 % (5/23) had abnormal looping. Bradycardia was also found in comparison with control embryos (P < 0.001). For the embryos treated with 0.25 mM valproic acid (group B), 92% (22/24) demonstrated chamber formation failure and looping abnormality. Pericardial effusion, noncontracting ventricles, and enlarged, slowly beating atriums were observed at 6 days postfertilization. Valproic acid inhibited phosphorylation of serine 9 in glycogen synthase kinase 3β in a dose-dependent manner. According to immunochemical staining results, valproic acid was shown to inhibit the mass migration and proliferation of cardiomyocytes in the development of the heart-valve region through inhibition of the GSK3β Ser 9 phosphorylation. Folic acid rescued the GSK3β Ser 9 phosphorylation and reversed the valproic acid-induced cardiac morphological, functional, and biochemical defects.[SDGs]SDG3journal article10.1007/s12012-015-9316-02-s2.0-84953365625