Effect of Diabetes and omega-3 Polyunsaturated Fatty Acids on the Quality of the Uterus in Mice (P09-007-19)

To evaluate the effect of diabetes and dietary supplementation with fish oil, rich in ω-3 PUFA, on the quality of the uterus in female C57Bl/6J mice. Forty female C57bl/6J mice with eight-week old were divided into four experimental groups: control (C), control treated with fish oil (CF), diabetic (D) and diabetic treated with fish oil (DF). Groups C and CF were fed a standard diet and the diabetic groups D and DF received a hyperlipidic diet. CF and DF groups received 3.5g/kg of fish oil 3 times a week for 10 weeks. At the end of the fourth feeding week, groups D and DF received streptozotocin (40mg/kg/day) for 5 consecutive days, and after one week another streptozotocin dose (100 mg/kg) was injected. The animals were submitted to the glucose and insulin tolerance tests and after were mated and the uterus collected 3,5 days after mating. Body mass gain, energy, food and water intake, serum levels of triglycerides and total cholesterol (TC), insulinemia, protein expression of proteins related to apoptosis, reticulum stress and autophagy, and uterine tissue histology were analyzed. The diabetic animals had increased fasting glucose, insulin resistance, glucose intolerance, reduced serologic levels of insulin, reduction of food consumption without alteration in energy consumption and increase of water consumption and TC. In the diabetic animals, there was also a reduction of activated caspase-3, LC3A/B, ubiquitin and endometrial and uterus areas. Treatment with fish oil improved insulin sensitivity, increased levels of these proteins and the areas of the endometrium and uterus. These data suggest that the decrease in the proteins related to apoptosis, autophagy and protein degradation in the uterus of diabetic animals may be one of the mechanisms by which DM decreases the endometrial thickness and consequently the success of the embryo implantation and additionally that the fish oil treatment can improve these parameters. Dietary supplementation with ω-3 PUFA may improve uterine quality and probably also female fertility, compromised in diabetic animals. Foundation for Research Support of the State of São Paulo (FAPESP); National Council for Scientific and Technological Development (CNPQ); Coordination of Improvement of Higher Level Personnel (CAPES).