{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:26:42Z","timestamp":1790533602918,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007123","name":"Stanley Medical Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007123","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":[[2019,8,15]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The anticonvulsant valproic acid (VPA) has a known teratogenic effect capable of inducing major congenital malformations and developmental disorders. A comparative teratogenicity study of VPA and its analog valnoctamide (VCD), which is a new generation candidate antiepileptic drug, was carried out using Swiss Vancouver (SWV) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant SWV dams were treated with either a single intraperitoneal injection of VPA (1.8 and 2.7 mmol\/kg), VCD (1.8 and 2.7 mmol\/kg), or vehicle on E8:12 (gestational day:hour). The numbers of implantation and resorption, viable and dead fetuses, and the presence of gross fetal visceral and skeletal abnormalities were determined (E18). Real\u2010time Polymerase chain reaction (RT\u2010PCR) arrays were used to analyze the expression of 84 genes related to the processes of neurogenesis and neural stem cell differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant decreases in pregnancy weight gain and the number of live fetuses were observed when VPA was administered at the high dose, whereas the percentage of exencephalic fetuses was significantly increased in VPA treated compared with an equivalent VCD dosage group. There was a dose\u2010related increase in visceral defects in the VPA\u2010exposed fetuses. Missing skull bones and fused vertebrae in fetuses occurred at the high dose of VPA. Three genes (<jats:italic>Mtap2<\/jats:italic>, <jats:italic>Bmp8b<\/jats:italic>, and <jats:italic>Stat3<\/jats:italic>) were significantly upregulated and one (<jats:italic>Heyl<\/jats:italic>) was downregulated in samples from VPA\u2010treated dams.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The study demonstrates that the teratogenicity of VPA was significantly greater than that of an equimolar dose of VCD. Four genes (<jats:italic>Mtap2<\/jats:italic>, <jats:italic>Bmp8b<\/jats:italic>, <jats:italic>Stat3<\/jats:italic>, and <jats:italic>Heyl<\/jats:italic>) represent candidate target genes for the underlying teratogenic mechanism responsible for VPA\u2010induced malformations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1406","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T13:05:44Z","timestamp":1539695144000},"page":"1013-1023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Teratogenicity of valproic acid and its constitutional isomer, amide derivative valnoctamide in mice"],"prefix":"10.1002","volume":"111","author":[{"given":"Ying Linda","family":"Lin","sequence":"first","affiliation":[{"name":"Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meir","family":"Bialer","sequence":"additional","affiliation":[{"name":"Institute of Drug Research, School of Pharmacy The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-5832","authenticated-orcid":false,"given":"Bogdan J.","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132814Y.0000000438"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90235-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071809"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199120020-00003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.11.006"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315032"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12004"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.10.027"},{"key":"e_1_2_6_10_1","first-page":"ID479364","article-title":"Molecular and therapeutic potential and toxicity of Valproic acid","author":"Chateauvieux S.","year":"2010","journal-title":"Journal of Biomedicine & Biotechnology"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001893"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1258\/jmb.2007.007042"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.058602"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06886.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420140302"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.10.023"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(94)90202-X"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198612000-00021"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1117"},{"key":"e_1_2_6_20_1","first-page":"753","article-title":"Clinical study of Valnoctamide on 70 neuropsychiatric clinic patients undergoing ambulatory treatment","volume":"72","author":"Harl F. 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