Metformin As a Potential Agent for Modulating the Faulty Endometriotic Mesenchymal Stem Cells: A Case-control Study

Overview

Journal Int J Reprod Biomed

Specialty Reproductive Medicine

Date 2022 Nov 16

PMID 36381355

Authors

Parisa Mashayekhi

Mehrdad Noruzinia

Sepideh Khodaverdi

Affiliations

Soon will be listed here.

Abstract

Background: According to stem cell theory, it seems that the proliferation/differentiation imbalance in endometrial mesenchymal stem cells (enMSCs) 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 enMSCs 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 3 endometriotic and 3 healthy women. After their characterization and culture, they were treated with 0.1, 1, and 10 mM metformin for 72 hr. Finally, the expression of octamer-binding transcription factor (OCT) 4A, OCT4B, OCT4B1, sex determining region Y-Box transcription factor 2, nanog homeobox, microRNA-200b, microRNA-145, and lethal-7b were analyzed by quantitative reverse transcription-polymerase chain reaction.

Results: Metformin modulated the expression of stemness-related genes and miRNAs, OCT4A, OCT4B, OCT4B1, sex determining region Y-Box transcription factor 2, nanog homeobox, microRNA-200b, microRNA-145, and lethal-7b in enMSCs, especially at 1 and 10 mM concentration. Notably, metformin had a paradoxical effect on normal enMSCs.

Conclusion: We showed that metformin could modulate the expression of deregulated genes and miRNAs in faulty enMSCs, and restore their skewed self-renewal/differentiation balance, so it might be a promising drug for endometriosis treatment. The paradoxical effect of metformin on enMSCs and normal enMSCs might be because of their different metabolic patterns, so it requires further investigation to illustrate.

Citing Articles

Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms.

Zhang P, Wang G Int J Mol Sci. 2023; 24(8).

PMID: 37108154 PMC: 10138736. DOI: 10.3390/ijms24086992.

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