Abstract
Background Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives We aimed to identify the differences in some genes' expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.
Highlights
Endometriosis is a benign inflammatory disease in women caused by the outgrowth of endometrial tissue outside the uterus [1, 2]
Flow cytometric analysis of passage 3 mesenchymal stem cells (MenSCs) demonstrated that both NE-MenSCs and E-MenSCs were positive for CD44, CD73, CD90, CD105, CD29, CD9, and CD10 expression but negative for CD34, CD45, CD133, and CD38 expression (Figure 1(b))
CD10 expression was significantly higher in E-MenSCs compared with NE-MenSCs, which can be considered as a useful marker in the diagnosis of endometriosis
Summary
Endometriosis is a benign inflammatory disease in women caused by the outgrowth of endometrial tissue outside the uterus [1, 2]. Evidence of studies showed that there are stem cells with high proliferation and differentiation potential in menstrual blood called menstrual blood-derived stem cells (MenSCs) These cells are morphologically and functionally similar to cells directly isolated from the endometrium and express both markers of mesenchymal and embryonic stem cells, such as Oct-4, SSEA-4, Nanog, c-kit (CD117), CD44, CD90, and CD105, as well [8,9,10,11]. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis
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