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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 Publisher



Zarei R1 ; Aboutorabi R1 ; Rashidi B1 ; Eskandari N2 ; Nikpour P3, 4
Authors

Source: International Journal of Reproductive BioMedicine Published:2020


Abstract

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. © Zarei et al.
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