1 Department of Gynecology and Obstetrics, University of Giessen, Giessen, Germany.
Lutz Konrad and Judith Gronbach contributed equally to the study.
Reprod Sci. 2019 Jan;26(1):49-59. doi: 10.1177/1933719118756745. Epub 2018 Feb 5.
Epithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial and acquisition of mesenchymal cell characteristics. Our aim was to assess the epithelial phenotype in the pathogenesis of endometriosis with epithelial and mesenchymal markers. We used 2 structural (keratin-18, -19 [K18, K19]), 1 membrane-associated (mucin-1 [MUC1]), and 2 mesenchymal proteins (vimentin; zinc finger E-box-binding homeobox 1, [ZEB1]) to compare epithelial and mesenchymal characteristics in eutopic endometrium with the 3 endometriotic entities, peritoneal, ovarian, and deep infiltrating endometriosis (DIE). Quantitation showed no differences for K18, K19, and MUC1 between endometrium with and without endometriosis. Also, K18 was not different between endometrium and endometriotic lesions. In contrast, K19 and MUC1 were modestly but significantly decreased in the endometriotic lesions compared to endometrium. However, the maintained expression of epithelial markers in all investigated tissues, regardless of the pathological condition, clearly indicates no loss of the epithelial phenotype. This is further supported by the reduced presence of epithelial vimentin in endometriotic lesions which is in contrast to an increase in stromal vimentin in ectopic endometrium, especially in ovarian endometriosis. The ZEB1 increase in endometriotic lesions, especially in DIE, on the other hand suggests a role of partial EMT in the development of endometriotic lesions, possibly connected with the gain of invasive capabilities or stemness. Taken together, although we found some hints for at least a partial EMT, we did not observe a severe loss of the epithelial cell phenotype. Thus, we propose that EMT is not a main factor in the pathogenesis of endometriosis.
上皮-间充质转化（EMT）的特征是上皮细胞特征的丧失和间充质细胞特征的获得。我们的目的是使用上皮和间充质标志物评估子宫内膜异位症发病机制中的上皮表型。我们使用了 2 种结构蛋白（角蛋白-18、-19 [K18、K19]）、1 种膜相关蛋白（黏蛋白-1 [MUC1]）和 2 种间充质蛋白（波形蛋白；锌指 E 盒结合同源盒 1，[ZEB1]）来比较在位子宫内膜和 3 种子宫内膜异位症实体，腹膜、卵巢和深部浸润性子宫内膜异位症（DIE）的上皮和间充质特征。定量分析显示，有或无子宫内膜异位症的子宫内膜中 K18、K19 和 MUC1 之间没有差异。此外，K18 在子宫内膜和子宫内膜异位症病变之间也没有差异。相比之下，K19 和 MUC1 在子宫内膜异位症病变中略有但显著降低。然而，无论病理状况如何，所有研究组织中上皮标志物的持续表达都清楚地表明上皮表型没有丢失。这进一步得到了以下证据的支持：在子宫内膜异位症病变中上皮波形蛋白的存在减少，而在异位子宫内膜中，尤其是在卵巢子宫内膜异位症中，基质波形蛋白增加。另一方面，ZEB1 在子宫内膜异位症病变中的增加，特别是在 DIE 中，表明 EMT 的部分作用可能与获得侵袭能力或干细胞特性有关。综上所述，尽管我们发现了一些至少部分 EMT 的迹象，但我们没有观察到上皮细胞表型的严重丧失。因此，我们提出 EMT 不是子宫内膜异位症发病机制的主要因素。
