Disease relevance of Dep1

• Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy [1].
• Although there are data to suggest that hyperglycemia itself is teratogenic, few mechanisms have been proposed to explain diabetic embryopathy [2].
• A sustained exposure of the fetus to such an environment (ie, elevated concentration of glucose), during the first 6 to 8 weeks of gestation in humans may result in diabetic embryopathy, which is characterized by a multitude of congenital birth defects, including those of the nervous, cardiovascular, skeletal, and urogenital systems [3].
• Maternal diabetes during pregnancy is responsible for the occurrence of diabetic embryopathy, a spectrum of birth defects that includes heart abnormalities, neural tube defects, and caudal dysgenesis syndromes [4].

High impact information on Dep1

• Glucose transporter-1-deficient mice exhibit impaired development and deformities that are similar to diabetic embryopathy [5].
• Thus, Pax3 haploinsufficiency in this murine model of diabetic embryopathy is associated with caudal but not cranial NTDs [6].
• The arachidonic acid cascade leading to prostaglandins has been implicated in diabetic embryopathy [7].
• These data suggest that the failure of neural tube fusion seen in diabetic embryopathy is mediated through a mechanism involving abnormalities in both the myo-inositol and arachidonic acid pathways, resulting in a functional deficiency of prostaglandins at a critical time of neural tube fusion [8].
• Investigation into the signaling mechanisms by which excess glucose metabolism exhibits toxic effects on embryo gene expression will explain how diabetic embryopathy occurs on a molecular and cellular level, as well as increase our understanding of the role of metabolic homeostasis in proper embryonic development [9].

Chemical compound and disease context of Dep1

• Arachidonic acid (AA) prevents neural tube/defects, cleft palate, and micrognathia in the rat models of diabetic embryopathy and neural tube defects in the mouse embryo culture model [10].

Biological context of Dep1

• Identification of Dep-1, a new gene regulated by the transcription factor Pax-3, as a marker for altered embryonic gene expression during diabetic pregnancy [11].
• Diabetic embryopathy in C57BL/6J mice. Altered fetal sex ratio and impact of the splotch allele [6].
• Impaired embryo gene expression resulting from oxidative stress, and consequent apoptosis or disturbed organogenesis, may be a general mechanism to explain diabetic embryopathy [12].
• The hypothesis that the hyperglycemia-induced decrease in glucose transport triggers apoptosis is presented and discussed as a novel mechanism to explain preimplantation diabetic embryopathy [13].
• Genotoxicity and diabetic embryopathy: impaired expression of developmental control genes as a cause of defective morphogenesis [9].

Anatomical context of Dep1

• Immunostimulation by complete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, or interferon-gamma reduces severity of diabetic embryopathy in ICR mice [14].

Analytical, diagnostic and therapeutic context of Dep1

• This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabetic rat and the in vitro hyperglycemic mouse embryo culture [15].

References