A novel rat model of gestational diabetes induced by intrauterine programming is associated with alterations in placental signaling and fetal overgrowth

EVANGELINA CAPOBIANCO; DAIANA FORNES; IVANA LINENBERG; THERESA L POWELL; THOMAS JANSSON; ALICIA JAWERBAUM

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 vol. 422 p. 221 - 232

0303-7207

A family history of diabetes predisposes to gestational diabetes mellitus (GDM). We hypothesized that female offspring of rats with pre-gestational diabetes will develop GDM, a pathology associatedwith fetal overgrowth and altered placental signaling. We found normal glycemia and insulinemia in the offspring from pre-gestational diabetic rats at three months of age. However, consistent with GDM, maternal hyperglycemia and hyperinsulinemia and increased fetal weight were evident when compared to controls. In this intrauterine programmed GDM model, the placentas showed alterations in mTOR pathway: unchanged phosphorylation of 4EBP-1 and PKCalpha despite reduced total expression of4EBP-1 and PKCalpha, and increased phosphorylation of SGK1. GDM placentas also showed reduced expression of PPARalpha and PPARgamma, and increased lipoperoxidation, nitric oxide production and peroxynitrite-induced damage. We conclude that exposure of maternal diabetes in utero programs GDM in the female offspring, leading to a GDM model associated with impaired placental signaling pathways, increased pro-oxidant/proinflammatory environment and fetal overgrowth.