A Maternal Diet Enriched In Extra Virgin Olive Oil Does Not Prevent Reduced Uteri Weight and Decidual PPAR Levels in The Offspring of Diabetic Rats.

GATTI, CINTIA R; ROBERTI SABRINA L; GOMEZ RIBOT DALMIRO; HIGA ROMINA; JAWERBAUM ALICIA

Congreso; Latin American DOHaD chapter 2020; 2020

Background and Aim: Maternal diabetes increases the risks of maternal, fetal and placentalcomplications and leads to the programming of metabolic and cardiovasculardiseases in the offspring. These alterations are in part related to a maternaldiabetes-induced prooxidant-proinflammatory intrauterine environment, which mayalter the uterus in the female offspring. Our recent studies have shown that adietary supplementation with extra virgin olive oil (EVOO) is able to reducemarkers of the prooxidant-proinflammatory state in the placenta and differentfetal organs in experimental models of diabetes and pregnancy. EVOO is highlyenriched in oleic acid, a monounsaturated fatty acid that activates PeroxisomeProliferator Activated Receptors (PPARs). PPARs are involved in decidualizationand anti-inflammatory processes. The aim of this work was to evaluate the uterusof the offspring of diabetic rats that receive or not an EVOO enriched dietduring pregnancy, evaluating the weight of decidualized and not-decidualizeduteri at a prepubertal age, as well as addressing PPARs expression in thedecidua at a postimplantation stage. Methods: A mild pregestational diabetic rat model was induced in F0 females byneonatal administration of streptozotocin (90 mg/kg sc). Control and diabeticfemales were mated with healthy males and were fed or not with a 6% olive oilenriched diet from day 1 of pregnancy until parturition. The offspring were feda standard diet and the uteri of the female offspring (F1) were evaluated a) ata prepuberal stage: 30 day postnatal, with or without induction ofdecidualization with PMSG (50 UI) and hCG (50 UI) and b) on day 9 of pregnancy.At the prepuberal stage non-decidualized and decidualized uteri were weighted,and on day 9 of pregnancy, the expression of PPARalpha, PPARgamma and PPARdeltawas evaluated in the decidua. Results: At a prepubertal stage, the offspring of diabetic rats(Diabetic Group) showed a reduction in weight in the non-decidualized uteri(36%, p<0.05 vs. Control Group). This alteration was not prevented by theEVOO enriched diet (27%, p<0.05 EVOO-Diabetic Group vs. EVOO-Control Group).The induction of decidualization increased the weight of the uteri of thediabetic rat offspring compared to the non-decidualized Diabetic Group (60%,p<0.001). The maternal diet enriched in EVOO did not change the weight ofthe uteri in the decidualized groups. At the postimplantation stage evaluated (day9 of pregnancy), there were no changes in the number of implantations and resorptionsin the evaluated groups. In the decidua, we found reduced protein expression ofPPARalfa, PPARgamma y PPARdelta (60%, 40%, 51% reduction respectively,p<0.05 vs. Control). The maternal EVOO diet did not change PPARs expressionin the evaluated groups. Conclusion: Maternal diabetes led to a reduced uteri weight in the prepubertaloffspring of female diabetic rats, an alteration that was not prevented by theEVOO enriched diet. The reduction in weight is not observed in the decidualizeduteri, suggesting an overstimulation of the decidual process in the diabeticgroup. During pregnancy, no changes were observed in the number ofimplantations and resorptions, but the expression of the three PPAR isotypesare reduced, which may affect the decidual function. The EVOO-supplemented dietdid not change PPAR levels in the evaluated groups, and further worksaddressing PPAR target genes are needed to address the putative capacity ofEVOO-supplemented diet to activate PPARs despite their reduced levels.