The influence of menstrual cycle and endometriosis on endometrial expression of epithelial-to-mesenchymal transition (EMT)-related genes

Background: Endometriosis is a common chronic gynaecological disorder related to the presence of ectopic foci of endometrial-like tissue mostly in the pelvic cavity. Pathogenesis of this disease may be associated with epithelial-to-mesenchymal transition (EMT), a phenomenon defined by morphological and functional changes from epithelial to mesenchymal cell phenotype. The role of EMT in development of endometriotic lesions remains poorly understood. There is also little known about a role of EMT in eutopic endometrium in course of the menstrual cycle. Therefore, the present study was aimed at investigating expression of major EMT-related genes of TGF-b, ZEB, SNAIL, CDH and miR200 families in eutopic endometrium of women with and without endometriosis in proliferative and secretory phase of the menstrual cycle. Methods: The study included 46 women with endometriosis and 30 control women without symptoms of the disease. Eutopic endometrial tissue samples were collected during mid-proliferative and mid-secretory phase. Tissue localization of the tested factors was detected by immunohistochemical staining. Expression of specific RNAs was evaluated by quantitative RT-PCR. Differences between groups were determined using the Student’s t -test, Wilcoxon matched-pairs signed rank test or Mann–Whitney U -test. Results: All investigated factors were expressed in eutopic endometrium both at the protein and mRNA level. Comparison of mRNA expression during different cycle phases has revealed a significant upregulation of SNAI2 mRNA in the secretory phase in both endometriosis and control group. Secretory phase was also associated with a decreased expression of CDH2 mRNA in the control group. However, similar difference was not revealed in the endometriosis patients. There were no differences in mRNA levels of the other tested EMT-related factors between endometriosis and control group regardless the cycle phase. Conclusions: The present study shows that SNAI2 expression is upregulated during secretory phase of the menstrual cycle thus suggesting its role in physiology of the cyclic endometrial changes. However, our data argue for a limited role of EMT in eutopic endometrium in the pathogenesis of endometriosis. These findings put a new light on the physiology of endometrium and the role of EMT in the pathogenesis of endometriosis.