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

IVANA LINENBERG, STUDENT; ALICIA JAWERBAUM ; DAIANA FORNÉS, PHD STUDENT; THOMAS JANSSON ; EVANGELINA CAPOBIANCO, PHD; THERESA L POWELL, PHD

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 gestationaldiabetes mellitus (GDM). We hypothesized that female offspring of ratswith pre-gestational diabetes will develop GDM, a pathology associatedwith fetal overgrowth and altered placental signaling. We found normalglycemia and insulinemia in the offspring from pre-gestational diabeticrats at three months of age. However, consistent with GDM, maternalhyperglycemia and hyperinsulinemia and increased fetal weight wereevident when compared to controls. In this intrauterine programmed GDMmodel, the placentas showed alterations in mTOR pathway: unchangedphosphorylation of 4EBP-1 and PKCα despite reduced total expression of4EBP-1 and PKCα, and increased phosphorylation of SGK1. GDM placentasalso showed reduced expression of PPARα and PPARγ, and increasedlipoperoxidation, nitric oxide production and peroxynitrite-induceddamage. We conclude that exposure of maternal diabetes in utero programsGDM in the female offspring, leading to a GDM model associated withimpaired placental signaling pathways, increased pro-oxidant/proinflammatoryenvironment and fetal overgrowth.