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The etiology of NTDs is complex, caused by interactions between genetic defects and environmental factors, but the exact mechanisms of this disease are still not fully understood. We herein employ a Seahorse Bioscience microplate\u2010based extracellular flux (XF) analyzer to determine mitochondrial function and quantify respiratory coupling to various bioenergetic functions using specific pharmacological inhibitors of bioenergetic pathways. We demonstrate that changes in coupling between ATP turnover and proton leak are correlated with NTDs. Further, we determined that the ATP content and oxidative stress levels in posterior spinal cords of rat embryos with NTDs between E11 and E14 was lower than that of normal controls. The present study reveals that mitochondrial dysfunction is associated with all\u2010trans retinoic acid (atRA)\u2010induced NTDs in rat embryos. Oxidative stress results from decreased antioxidant enzyme activity. This study provides a novel viewpoint for exploring the embryonic pathogenesis of atRA\u2010induced NTDs.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2018.04.003","type":"journal-article","created":{"date-parts":[[2018,4,22]],"date-time":"2018-04-22T20:56:16Z","timestamp":1524430576000},"page":"39-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mitochondrial dysfunction is implicated in retinoic acid\u2010induced spina bifida aperta in rat fetuses"],"prefix":"10.1002","volume":"68","author":[{"given":"Jia","family":"Xue","sequence":"first","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianshuai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1242\/jeb.203.23.3603","article-title":"Processes contributing to metabolic depression in hepatopancreas cells from the snail Helix aspersa","volume":"203","author":"Bishop T.","year":"2000","journal-title":"J. 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