Regulation of mTOR pathway in the decidua from diabetic rats by maternal diets enriched in sunflower and chia oil during early organogenesis

SATO HUGO; ROBERTI SABRINA L; HIGA ROMINA; GATTI CINTIA R; JAWERBAUM ALICIA

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Embryo development defects induced by maternal diabetes may start at early pregnancy when histotrophic nutrition occurs through the decidua. Leukine inhibitor factor (LIF) and insulin growth factor binding protein 1 (IGFBP1) participate in decidualization and development. Mammalian target of rapamycin (mTOR) pathway senses nutrient availability and is regulated by polyunsaturated fatty acids (PUFAs). Aim: evaluate mTOR pathway, LIF and IGFBP1 gene expression in the decidua of diabetic rats at day 9 of pregnancy and the effect of diets enriched in sunflower and chia oil (enriched in n-6 and n-3 PUFAs respectively) at early postimplantation on these parameters. Methods: diabetes was induced by streptozotocin (50 mg/kg) in female Wistar rats 2 weeks before mating. On days 7,8 and 9 of pregnancy diabetic rats received a standard diet or diets enriched in 6% of sunflower or chia oil. In the decidua of 9-days-pregnant rats mRNA levels of LIF, IGFBP1 and mTOR were measured by RT-qPCR and protein levels of 4EBP1, rpS6 and AKT (proteins downstream mTOR pathway) were measured by Western Blot. 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). PUFA-enriched diets prevented the reduced IGFBP1 mRNA levels and sunflower enriched diet also prevented the reduced LIF and IGFBP1 gene expression. Phosphorylated protein levels of 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 diets restored the phosphorylated/total levels ratio of these proteins. Conclusion: the inhibition of the mTOR pathway and the low expression of LIF and IGFBP1 suggest impairments in decidualization and regulation of histotrophic nutrition at early postimplantation in diabetic rats. These alterations were prevented by PUFA-enriched diets suggesting benefits of these dietary treatments for early postimplantation development in maternal diabetes.