Background: According to stem cell theory, it seems that the proliferation/differentiation imbalance in endometrial mesenchymal stem cells (eMSCs) is the leading cause of endometriosis, so targeting them to modulate stemness-relevant factors seems to be a wise choice for endometriosis treatment.
Objective: We aimed to investigate the effects of metformin on stemness properties of eMSCs by evaluating the expression profile of stemness-related genes and microRNAs (miRNAs).
Materials and Methods: In this case-control study, MSCs were isolated from the eutopic endometrium of ۳ endometriotic and ۳ healthy women. After their characterization and culture, they were treated with ۰.۱, ۱, and ۱۰ mM metformin for ۷۲ hr. Finally, the expression of octamer-binding transcription factor (OCT) ۴A, OCT۴B, OCT۴B۱, sex determining region Y-Box transcription factor ۲, nanog homeobox, microRNA-۲۰۰b, microRNA-۱۴۵, and lethal-۷b were analyzed by quantitative reverse transcription-polymerase chain reaction.
Results: Metformin modulated the expression of stemness-related genes and miRNAs, OCT۴A, OCT۴B, OCT۴B۱, sex determining region Y-Box transcription factor ۲, nanog homeobox, microRNA-۲۰۰b, microRNA-۱۴۵, and lethal-۷b in eMSCs, especially at ۱ and ۱۰ mM concentration. Notably, metformin had a paradoxical effect on normal eMSCs.
Conclusion: We showed that metformin could modulate the expression of deregulated genes and miRNAs in faulty eMSCs, and restore their skewed self-renewal/differentiation balance, so it might be a promising drug for endometriosis treatment. The paradoxical effect of metformin on eMSCs and normal eMSCs might be because of their different metabolic patterns, so it requires further investigation to illustrate.