1210-P: Maternal Diets Enriched in Olive Oil Prevent Altered Regulation of mTOR Pathways in the Decidua of the Prepubertal Offspring of Diabetic Rats

Introduction & Objective: Maternal diabetes can program offspring´s diseases. mTOR pathway is crucial in decidualization, needed for properly early embryo development. In a rat model of pregestational diabetes, the female offspring showed reduced decidual levels of microRNA-21 (miR21), a microRNA involved in decidualization, an alteration prevented by a maternal diet enriched in olive oil. Here, we aim to evaluate targets of miR21 related to mTOR pathway regulation in the decidualized uteri of prepubertal offspring of diabetic rats fed or not with an olive oil-enriched diet.

Methods: A mild pregestational diabetic rat model was induced in F0 females by neonatal administration of streptozotocin (90 mg/kg sc). Control and diabetic females, mated with healthy males, received or not a 6% olive oil-enriched diet from day 1 of pregnancy until parturition. Female offspring (F1) were evaluated on postnatal day 30, after induction of decidualization (PMSG 50 UI- hCG 50 UI). MiR-21 targets PTEN and FOXO1, mTOR pathway negative regulators, were evaluated by RT-qPCR and mTOR pathway activity was evaluated by Western Blot.

Results: The offspring of diabetic rats showed increased PTEN and FOXO1 gene expression in the decidualized uteri (1.54 and 1.68 fold-change respectively, p<0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet. They also showed altered activity of mTOR pathway: reduced phosphorylated-rpS6/total rpS6 ratio (-75%) and phosphorylated-4EBP1/total 4EBP1 ratio (-56%) (p<0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet.

Conclusions: In the decidualized uteri of diabetic rat offspring, increased expression of miR21 target genes that negatively regulate mTOR activity and reduced mTOR activity suggest diabetes-induced programming of dysregulation of a signaling pathway relevant for decidualization, that can be prevented by a maternal olive oil-enriched diet.