Effect of maternal diets enriched in sunflower or chia oil on mTOR pathway in the decidua of diabetic rats during early postimplantation

SABRINA LORENA ROBERTI; CINTIA ROMINA GATTI; ROMINA HIGA; ALICIA JAWERBAUM

Simposio; International Symposium on Reproductive Health 2021; 2021

Embryo development defects induced by maternal diabetes may start at early pregnancywhen histotrophic nutrition occurs through the decidua. Leukine inhibitor factor (LIF), insulingrowth factor binding protein 1 (IGFBP1) and matrix metalloproteinases (MMPs) participate indecidualization and development. Mammalian target of rapamycin (mTOR) pathway sensesnutrient availability and may be regulated by polyunsaturated fatty acids (PUFAs). Aim: Toevaluate the effect of diets enriched in sunflower and chia oil (enriched in n-6 and n-3 PUFAsrespectively) on mTOR pathway, LIF and IGFBP1 gene expression and MMPs activity in thedecidua of diabetic rats at day 9 of pregnancy. Methods: pregestational diabetes was inducedin Wistar rats by streptozotocin administration (50 mg/kg). On days 7,8 and 9 of pregnancydiabetic rats received a standard diet or diets enriched in 6% of sunflower or chia oil. In thedecidua of 9-days-pregnant rats we measured mRNA levels of LIF, IGFBP1 and mTOR byRT-qPCR, protein levels of 4EBP1, rpS6 and AKT (proteins downstream mTOR pathway) byWestern Blot and MMPs activity by in situ zymography. Results: The mRNA levels of LIF,IGFBP1 and mTOR were reduced in the decidua of diabetic rats (p<0.001, 71%; p<0.05,34%; p<0.05, 54%; respectively). Both diets prevented the reduced IGFBP1 mRNA levels.Sunflower-enriched diet prevented the reduced LIF expression. Phosphorylated protein levelsof 4EBP1, rpS6 and AKT were reduced in the diabetic group (p<0.05, 27%; p<0.05, 40%;p<0.05, 14%; respectively), with no changes in total protein levels. PUFA-enriched dietsrestored the phosphorylated/total levels ratio of these proteins. MMPs activity was reduced inthe decidua and ectoplacental cone in diabetic rats (p<0.05), an alteration prevented by thePUFAs-enriched diets. Conclusion: Our results suggest impairments in decidualization andhistotrophic nutrition regulation at early postimplantation in diabetic rats, which can beprevented by maternal diets enriched in PUFAs.