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Nevertheless, how these two factors might interact in the development of NTDs remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In specific mouse models and embryo culture systems, we assessed the effects of combining maternal diabetes with mutations in genes involved in folate transport and metabolism (methylenetetrahydrofolate reductase [<jats:italic>Mthfr<\/jats:italic>] and folic acid receptor 1 [<jats:italic>Folr1<\/jats:italic>]). When maternal hyperglycemia is combined with alterations in folic acid metabolism, there appears to be an increase in the incidence of congenital malformations in the offspring, with NTDs representing the majority of the malformations detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The teratogenic effects of diabetes during pregnancy are exacerbated when combined with altered embryonic folate metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.92","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T11:48:46Z","timestamp":1564487326000},"page":"900-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The interaction of maternal diabetes with mutations that affect folate metabolism and how they affect the development of neural tube defects in mice"],"prefix":"10.1002","volume":"248","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-1830","authenticated-orcid":false,"given":"Beatriz","family":"L\u00f3pez\u2010Escobar","sequence":"first","affiliation":[{"name":"Neurodevelopment Research Group Institute of Biomedicine of Seville\/Hospital Virgen del Rocio\/US\/CSIC  Sevilla Spain"},{"name":"Department of Nutritional Sciences Dell Pediatric Research Institute, The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan J.","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Dell Pediatric Research Institute, The University of Texas at Austin  Austin Texas USA"},{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-3485","authenticated-orcid":false,"given":"Jose","family":"Caro\u2010Vega","sequence":"additional","affiliation":[{"name":"Neurodevelopment Research Group Institute of Biomedicine of Seville\/Hospital Virgen del Rocio\/US\/CSIC  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Dell Pediatric Research Institute, The University of Texas at Austin  Austin Texas USA"},{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Dell Pediatric Research Institute, The University of Texas at Austin  Austin Texas USA"},{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-2659","authenticated-orcid":false,"given":"Patricia","family":"Ybot\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Neurodevelopment Research Group Institute of Biomedicine of Seville\/Hospital Virgen del Rocio\/US\/CSIC  Sevilla Spain"},{"name":"Department of Neurology and Neurofisiology Hospital Virgen de Macarena  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.93"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01174.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2014.08.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1155"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788453069"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20056"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.017723"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-274"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/13861"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20680"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K07-117"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.85.1.1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20704"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1974.tb03442.x"},{"key":"e_1_2_7_16_1","first-page":"980","article-title":"Etiologic heterogeneity of neural tube defects. 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