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However, its protective role on the neural tube defects (<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg\/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (<jats:styled-content style=\"fixed-case\">NSC<\/jats:styled-content>s) under hyperglycemic condition through the extracellular regulated protein kinases (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of <jats:styled-content style=\"fixed-case\">NSC<\/jats:styled-content>s exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy.<\/jats:p>","DOI":"10.1111\/jpi.12282","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T13:03:48Z","timestamp":1444223028000},"page":"508-517","source":"Crossref","is-referenced-by-count":42,"title":["Melatonin prevents neural tube defects in the offspring of diabetic pregnancy"],"prefix":"10.1111","volume":"59","author":[{"given":"Shangming","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Pathophysiology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology Department of Histology and Embryology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2337\/diab.28.4.292","article-title":"Malformations in infants of diabetic mothers occur before the seventh gestational week. 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