title: Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy.
abstract: Maternal diabetes increases the risk for neural tube, and other, structural defects. The mother may have either type 1 or type 2 diabetes, but the diabetes must be existing at the earliest stages of pregnancy, during which organogenesis occurs. Abnormally high glucose levels in maternal blood, which leads to increased glucose transport to the embryo, is responsible for the teratogenic effects of maternal diabetes. Consequently, expression of genes that control essential developmental processes is disturbed. In this review, some of the biochemical pathways by which excess glucose metabolism disturbs neural tube formation are discussed. Research from the author's laboratory has shown that expression of Pax3, a gene required for neural tube closure, is significantly reduced by maternal diabetes, and this is associated with significantly increased neural tube defects (NTD). Pax3 encodes a transcription factor that has recently been shown to inhibit p53-dependent apoptosis. Evidence in support of this model, in which excess glucose metabolism inhibits expression of Pax3, thereby derepressing p53-dependent apoptosis of neuroepithelium and leading to NTD will be discussed.
authors.affiliation: Section on Developmental and Stem Cell Biology at Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. mary.loeken@joslin.harvard.edu
authors.forename: Mary R
authors.initials: MR
authors.lastname: Loeken
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D048909:Diabetes Complications; D047108:Embryonic Development; D005260:Female; D009436:Neural Tube Defects / Q000209:etiology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse