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

Document Type : Original Article

Authors

1 Department of Anatomical Sciences, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

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 1diabetes, 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, metformin 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 Muc1 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

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