Evaluation of vascular endothelial growth factor A and leukemia inhibitory factor expressions at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone

Implantation requires intimate crosstalk between the embryo and uterus for a successful establishment of pregnancy. Type 2 diabetes mellitus may lead to implantation failure. The effect of diabetes and its therapeutic drugs on implantation is still largely unclear. To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone. Twenty-eight 6-8-wk-old Wistar female rats weighing 200-250 gr were divided into four groups (n = 7/each). Type 2 diabetes was induced and Metformin and Pioglitazone were applied for 4 wk. The expression of VEGFA and LIF was measured by real-time reverse transcription-polymerase chain reaction and Western blot. The relative expression of VEGFA transcript was higher in the diabetic (p = 0.02) and Metformin-treated (p = 0.04) rats compared to the control group. Furthermore, the VEGFA transcript level significantly reduced in Pioglitazone-treated diabetic rats (p = 0.03). LIF expression was elevated in the Metformin- and the Pioglitazone-treated rats and reduced in the diabetic group in comparison with the control group. Compared to the diabetic rats, the expression of LIF was significantly elevated in the Metformin- (p = 0.01) and Pioglitazone-treated (p = 0.03) groups. The expressions of LIF and VEGFA were altered in diabetic rats during implantation which may be associated with diabetic-related infertility. Pioglitazone is able to restore the VEGFA and LIF expressions to their baseline levels more efficiently than Metformin.