Evaluation of Muc1 Gene Expression at The Time of implantation in Diabetic Rat Models Treated with Insulin, Metformin and Pioglitazone in The Normal Cycle and Ovulation Induction Cycle

Abstract

Background: Mucin-1(Muc1) is one of the first molecules in the endometrium that confronts implanting embryos. There is insufficient knowledge about the impacts of diabetes and drugs developed for diabetes treatment on expression of this molecule at the time of implantation. Therefore, this study aimed to investigate the impacts of diabetes and insulin, metformin and pioglitazone on Muc1 expression at the time of implantation. Materials and Methods: This experimental study was conducted on a total of 63 female Wistar rats divided into 9 groups. To induce type ldiabetes, streptozotocin (STZ) and for induction of type 2 diabetes, nicotinamide (NA) and STZ were injected intraperitoneally. For superovulation, human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) were used. Insulin, metfonnin and pioglitazone were administered for two weeks. Finally, the endometrial expression of Muc1 was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Muc1 expression was non-significantly increased in type 1 and type 2 diabetic groups compared to the control group (P=0.61 and 0.13. respectively); also, it increased in insulin-treated type 1 diabetic group compared to the control group (P=0.0001). Its expression was increased in insulin-treated type 1 diabetic group compared to untreated diabetic group (P=0.001). The expression level of Mud was significantly reduced in superovulated and insulin-treated type 1 diabetic group compared to the insulin-treated type 1 diabetic group (P=0.001). Conclusion: One of the causes of fertility problems in diabetes, is changes in Muc1 expression during implantation. On the other hand, the use of insulin in these patients can even lead to overexpression of this gene and worsen the condition. However, these changes can be partially mitigated by assisted reproductive technology (ART) such as superovulation. Also, treatment with metformin and pioglitazone can restore Muc1 expression to near normal levels and has beneficial effects on implantation.