P7 The addition of polyunsaturated fatty acids in the early postimplantation period prevents embryo resorptions and decidual anomalies in pregnant rats with diabetes

Abstract

Introduction: Pregestational diabetes increases the risk of embryo resorptions and impairs embryo development, which in turn may lead to fetal programming. The function of the decidua is crucial for the early postimplantation development, but little is known about possible anomalies in the decidua in maternal diabetes. Previously, we evidenced that the mTOR pathway in the decidua is relevant for the embryo growth and development. We also evidenced that the mTOR pathway interacts with the PPAR pathway, whose agonists have lipid nature and include polyunsaturated fatty acids (PUFAs).

Objective: To determine the resorption rate and to evaluate the mTOR pathway, as well as functional and tissue remodeling markers in the decidua of rats with pregestational diabetes that were fed or not with diets enriched in PUFAs exclusively during the early postimplantation period.

Methods: Control rats and rats with diabetes were mated with healthy males. Diabetes was induced before mating by streptozotocin injection (50 mg/kg). On days 7, 8 and 9 of pregnancy rats were fed a diet enriched or not in 6% sunflower oil or 6% chia oil (enriched in n-6 or n-3 PUFAs, respectively). On day 9 of pregnancy, the embryo resorption rate was determined and the decidua was collected to study the mTOR pathway, the expression of FoxO1, the levels of microRNA-21 (miR-21), as well as markers of decidual function and tissue remodeling (LIF and IGFBP1 expression and gelatinolytic activity of matrix metalloproteinases (MMPs).

Results: Maternal diabetes increased the embryo resorption rate (11%, p<0.01 v. control). Both diets enriched in PUFAs prevented the diabetes-induced increased in embryo resorption rate despite no changes in maternal glycemia. In the decidua from rats with diabetes, the mTOR pathway (evaluated by the mTOR expression and the
phosphorylation of proteins downstream mTOR signaling) was found reduced (p<0.05 v. control). The diets enriched in sunflower or chia oil prevented these anomalies. In the decidua from rats with diabetes, the expression of FoxO1 (negative regulator of mTOR) was increased (p<0.05 v. control) and the expression of miR-21 (negative regulator of FoxO1) was reduced (p<0.05 v. control). These alterations in FoxO1 expression and miR-21 levels were prevented by the diets enriched in PUFAs. The PUFAs-enriched
diets were also able to prevent the reduced LIF and IGFBP1 expression as well as the reduced MMPs activity in the decidua of rats with diabetes.

Conclusions: We identified the relevance of the early postimplantation period in the processes of embryo resorption induced by maternal diabetes. We evidenced the capacity of maternal diets enriched in PUFAs to prevent embryo resorptions, anomalies in decidual mTOR signaling and altered functional and remodeling markers in the decidua. These results suggest a putative benefit of diets enriched in PUFAs administrated during early postimplantation for the embryo development in maternal diabetes.