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Nonspecific stimulation of the mother's immune system has been shown to reduce various teratogen\u2010induced fetal malformations including<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s in rodents. This present study investigated the role of reduced apoptosis by maternal immune stimulation in prevention of<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010induced<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s in<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\u20101 mice. Prevention of<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010induced<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s by nonspecific maternal immune stimulation using<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b3 was employed to evaluate the role of reduced apoptosis by<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b3 in this protective mechanism. Apoptosis was quantified using flow cytometry. Terminal Transferase d<jats:styled-content style=\"fixed-case\">UTP<\/jats:styled-content>Nick End Labeling assay was used to localize the apoptosis. Increased apoptosis, suggesting involvement in<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>teratogenicity, was observed along the neural tube in both normal and abnormal embryos from<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010exposed dams. Increased apoptosis in normal<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010exposed embryos suggests that<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>may alter other cellular processes such as cell proliferation and differentiation in addition to apoptosis. Apoptotic levels in embryos with closed neural tubes from<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b3 +<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>dams were similar to controls indicating resistance to<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010induced apoptosis and protection against teratogenicity of<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>. In<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b3 +<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>exposed embryos with open neural tubes, maternal immune stimulation failed to regulate apoptosis resulting in an<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>. Overall, these results suggest that<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>alters several biological processes including apoptosis in the developing embryos to induce fetal malformations. Resistance to<jats:styled-content style=\"fixed-case\">VA<\/jats:styled-content>\u2010induced apoptosis in embryos resulting from maternal immune stimulation may be involved in protective mechanism.<\/jats:p>","DOI":"10.1002\/bdrb.21018","type":"journal-article","created":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T01:56:43Z","timestamp":1341539803000},"page":"296-303","source":"Crossref","is-referenced-by-count":12,"title":["Reduction in Valproic Acid\u2013Induced Neural Tube Defects by Maternal Immune Stimulation: Role of Apoptosis"],"prefix":"10.1002","volume":"95","author":[{"given":"Mural","family":"Mallela","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yale University New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Hrubec","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences E. 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