Characterization of Cell Types in the Endometrium and Endometriosis

Abstract

The human endometrium is composed of several different cell types which can be categorized into stromal and epithelial cells, which are only moderately characterized. Endometriosis is a disease characterized by presence of endometrial glands and stroma outside of the uterus. Irespective of location, endometriotic glands almost always resemble uterine endometrial glands. However, it is puzzling, that endometriotic lesions show variations in colour, depth of invasion, adhesions, ovarian cysts, and different epithelial to stromal cell ratios to extreme case of stromal endometriosis. To analyse which cell types are involved in pathogenesis of endometriosis, we characterized stromal composition and assessed epithelial phenotype in order to evaluate epithelial-mesenchymal transition (EMT), which is characterized by loss of epithelial and acquisition of mesenchymal cell characteristics. Quantification of eutopic endometrial stroma of non endometric cases showed a high percentage of stromal cells positive for CD140b (80.7%), and CD10 (67.4%), a moderate number of CD90-positive cells (57.9%) and very few α-smooth muscle actin-positive cells (8.5%). These values are highly similar to cases with minimal differences. There were are no significant differences in the composition of CD140b and CD10-positive stromal cells between the eutopic endometrial stroma and the three different endometriotic entities (ovarian, peritoneal and deep infiltrating endometriosis), except for a significant difference between CD10-positive stromal cells in peritoneal compared to ovarian lesions. There were no differences in keratin 18 (K18), K19 and mucin-1 (MUC1) content between endometrium with and without endometriosis. Although no difference was observed in K18 levels in endometrium and endometriotic lesions. K19 and MUC1 were significantly decreased in the endometriotic lesions compared to endometrium. Expression of epithelial markers in all investigated tissues, regardless of the pathological condition, clearly indicates no loss of the epithelial phenotype. The ZEB1 increase in endometriotic lesions, especially in deep infiltrating endometriosis, on the other hand suggests a role of partial EMT in the development of endometriotic lesions, possibly connected with of invasive capabilities or stemness. Taken together, the marker signature of eutopic endometrial and endometriotic stromal cells resembles mostly mesenchymal stromal cells and the proportion of the different stromal cell types in the endometrium with or without endometriosis does not differ significantly. This suggests that the stromal eutopic endometrial microenvironment does not contribute to pathogenesis of endometriosis. Although we found some hints for partial EMT, we did not observe severe loss of the epithelial cell phenotype. Hence, we propose, that EMT is not a main factor in the pathogenesis of endometriosis. Keywords: Cell types, endometrium,endometriosis.