Background: 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. Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. Key words: Embryo implantation, Leukemia inhibitory factor, Vascular endothelial growth factor A, Metformin, Pioglitazone, Rats.
Background:Diabetes, a major metabolic disorder, seems to affect the fertility rates of women in various ways. Due to the uncertainty of the effects of diabetes along with superovulation treatment on the infertility, we investigate the effects of ovulation induction treatment as therapeutic approach on the expression of leukemia inhibitory factor (LIF) and vascular endothelial growth factor A (VEGFA) as two main factors which are involved in the implantation in the streptozotocin (STZ)-induced type 1 diabetic rats.Materials and Methods:Type 1 diabetes was induced by injections of STZ in Wistar rats. The animals were kept in diabetic conditions for 4 weeks, while some were treated with insulin for treatment. After treatment, the ovulation was induced by human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). The rats were then sacrificed and the expression of LIF and VEGFA was checked by immunohistochemistry staining method, and the relative expression of LIF and VEGFA was measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting methods.Results:It was observed that diabetes and insulin treatment for diabetes altered the expression of Lif and VEGFA in both mRNA and protein levels. However, superovulation treatment seems to ameliorate this alternation for both factors.Conclusion:According to our results, diabetes and insulin therapy could alter the expression of Lif and VEGFA genes and proteins that are effective in endometrial receptivity and implantation process. It seems in diabetic cases, the effect of hCG and hMG therapy by itself could regulate the level of expression and presence of these two genes and proteins.
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