simposio: Novel model of GDM induced by intrauterine programming

JAWERBAUM A

Manchester

Congreso; International Federation of Placenta Associations 2017 (IFPA 2017); 2017

Maternal diabetes programs metabolic and cardiovascular diseases in the offspring. In our laboratory, by evaluating the offspring of mild diabetic pregnant rats, we have found increased markers of a pro-oxidant/proinflammatorystate in the heart from the neonatal stage and increased triglyceridemia from weaning. We have also found that the offspring of mild diabetic rats develop type 2 diabetes from the fifth month of age. As it is well known that a family history of GDM predisposes to type 2 diabetes, we hypothesized that the offspring of diabetic rats, which are normoglycemic at 3 months of age, would develop GDM if mated with normal males.This led us to obtain a GDM model through intrauterine programming in the offspring of mild diabetic rats. This GDM rat model is characterized byhyperglycemia and hyperinsulinemia in both mothers and fetuses. Fetuses from GDM mothers are increased in weight, although no changes in weightare evident in the placenta. Markers of a pro-oxidant/proinflammatory state are evident in the placenta, which shows reduced PPAR signaling andincreased mTOR signaling. Maternal treatments in the F0 generation with diets enriched in unsaturated fatty acids, which stimulate PPAR pathways,ameliorate the pro-oxidant/proinflammatory state in the placenta of the F1 generation. Antioxidant/anti-inflammatory effects on F1 placentas ofGMD mothers are also evidenced when the F0 mothers are treated with mitochondrial antioxidants during pregnancy. In conclusion, in a novelGDM model obtained through intrauterine programming, we have identified the ability of maternal F0 treatments to prevent the increased prooxidant/proinflammatory state in GDM rat placentas, which highlights the role of oxidative stress in the intrauterine programming of the placental alterations in a next generation.