Placental alterations in a new experimental model of gestational diabetes generated by intrauterine programming in the offpspring of mild diabetic rats

CAPOBIANCO E, FORNES D, PELESSON M, WHITE V, JAWERBAUM A

Paris

Congreso; International Federation of Placenta Associations 2014; 2014

IFPA

Gestational diabetes mellitus (GDM) is a prevalent disease that affects fetal and placental development and lacks appropriate experimental models for its study. In experimental models of pregestational mild diabetes both fetal and placental development are altered. Their offsprings are normoglucemic at birth and in young adults at reproductive age. We hypothesized that GDM can be developed in these offsprings if female are mated, providing a GDM experimental model with altered maternal and fetal serum parameters and placental alterations similar to those found in GDM patients. Methods: Pregestational diabetes was generated by neonatal streptozotocin administration. Female diabetic and control rats were mated with control males. Their offspring (first generation) was mated with control males and at day 21 of pregnancy, maternal and fetal serum was obtained and the placenta explanted. Glucose and insulin were measured in the sera, and lipoperoxidation (by TBARS) and the expression of PPARs (nuclear receptors involved in metabolic homeostasis and pro-oxidant/pro-inflammatory processes, by RT-PCR,) were determined in the placenta. Results: Although normoglucemic at the beginning of pregnancy, the offspring of diabetic rats develop gestational diabetes, showing hyperglycemia (p lower than 0.05) and hyperinsulinemia (p lower than 0.05) at day 21 of pregnancy. The female (p lower than 0.01) and more markedly the male (p lower than 0.001) fetuses also showed hyperglycemia (p lower than 0.05) and hyperinsulinemia. The placenta from both female and male fetuses showed increased lipoperoxidation (p lower than 0.05) and reduced expression of PPARgamma and PPARalpha, although no changes in the expression of PPARdelta and PPARgamma coactivator -1 were detected. Conclusions: Experimental pregestational diabetes can program GDM in their offsprings. This GDM model presents hyperglycemia and hyperinsulinemia and affects both the fetus and the placenta. The GDM placenta showed increased oxidative stress and reduced expression of PPARalpha and PPARgamma, therefore providing a new GDM model that shows similar alterations that those evident in GDM patients, which is now available for further studies of this disease.