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THE INFLUENCE OF HYPERGLYCEMIA ON EMBRYONIC GENE EXPRESSION IN DIABETIC MICE

Maternal diabetes increases the rate of congenital malformations in embryos, causing diabetic embryopathy. Although the cellular and molecular mechanisms of diabetic embryopathy are poorly understood, it was shown that maternal hyperglycemia increases oxidative stress in embryos. In our study, we have employed non-obese diabetic (NOD) mouse strain as a model of diabetic embryopathy. We analyzed embryo morphology from non-diabetic and alloxan-induced diabetic pregnancies, as well as expression of genes related to metabolism of reactive oxygen species (ROS) and neurogenesis, by RT-PCR and whole mount in situ hybridization. Maternal diabetes induced neural tube defects (NTDs) in 11% of NOD embryos, with exencephaly as the most prevailing defect. We have detected significant, more than twofold down-regulation of Bmp8b, Cdk5rap2, Hdac4, Hey2, Pou4f1 and Sox3 genes in embryos with exencephaly. In contrast, hyperglycemia did not influence the expression of ROS-scavenging genes. Therefore, maternal diabetes in NOD strain acts by altering the expression of transcription regulators which are involved in proliferation and differentiation of neural stem cells, thus influencing the neural tube closure according to multifactorial “threshold” model.

NOD; diabetic embryopathy; exencephaly; NTDs

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