[Recent advances in the pathogenesis of diabetic embryopathy]

The congenital malformations in the off spring of diabetic mothers are the result of a multifactorial process. Susceptibility to the effects of maternal diabetes in the pathogenesis of these anomalies is influenced by the genetic background, indicating that there are polymorphic genes that modify the cellular response to hyperglycemia. The modifier genes for the teratogenic effect of maternal diabetes are yet unknown. An excessive glucose supply to embryonic tissues leads to a state of oxidative stress, which affects the expression of genes encoding scavenging enzymes such as super oxide dismutase (SOD) and catastases and activates development genes such as PAX3, involved in neural tube defects. Cell proliferation and cell death are important mechanisms underlying malformations in infants born to diabetic mothers. There is an increase of apoptotic Bax and caspase-3 proteins and a low expression of Bcl-Z ant apoptotic protein in embryos exposed to a diabetic environment. Hyperglycemia decreases intracellular levels of reduced GSH, prostaglandin EZ (PGEZ) and DNA synthesis in embryo's tissues. Understanding the molecular pathogenesis of diabetic embryopathy will allow the use of effective therapies for the prevention of teratogenic effects in diabetic mothers.