The hyperexpressions of putative stem cells in the eutopic endometrium of patients with advanced endometriosis / 대한산부인과학회지

ABSTRACT

OBJECTIVE: Recently it has been proposed that stem cells may be associated with the pathogenesis of endometriosis. The purposes of this study are to investigate whether the eutopic endometrial cells of women with or without endometriosis show the characteristics of stem cells in vitro and have a difference of the expressions of the undifferentiated stem cell markers as OCT-4 and CXCR4. METHODS: A total of 6 women with advanced endometriosis and a total of 10 women without endometriosis, adenomyosis or leiomyoma were included in this study. The eutopic endometrial cells, which were obtained from the menstrual blood at menstrual cycle day 2 to 4, were cultured in vitro for approximately 2 weeks, subsequently the putative very small stem cells were separated by Percoll density gradient method and were cultured. The expressions of OCT-4 and CXCR4 were analyzed by real time RT-PCR. RESULTS: The eutopic endometrial cells of the group of endometriosis compared with the control group showed the different morphological characteristics in vitro; more commonly heterogeneous supportive cells, very small round cells less than 3 micrometer and 5~15 micrometer sized hyperchromatic round cells. After the separation of very small round cells by Percoll density gradient method, these cells showed the several characteristics of stem cells; self-renewal, asymmetric cell division, colony formation and embryoid body-like formation. Also These cells showed the similar characteristics of very small embryonic-like stem cells; the mobile cells smaller than erythrocyte, the cell migration or adhesion to supportive cells, the sphere formation by cell aggregation and the formation of new differentiated cell by cell fusion. The expressions of OCT-4 and CXCR4 in the group of endometriosis are respectively 5.66 times and 17.69 times as high as the control group (P<0.05). CONCLUSION: The very small round cells less than 3 micrometer and 5~15 micrometer sized hyperchromatic round cells, which showed the several characteristics of stem cells in vitro, were more common in eutopic endometrial cells of patients with endometriosis and the expressions of OCT-4 and CXCR4 were significantly higher. This study suggests that stem cells might play a key role in the pathogenesis of endometriosis and OCT-4 and CXCR4 might be used as a tool for diagnosis or follow-up.