Localization of claudin-2 and claudin-3 in eutopic and ectopic endometrium is highly similar

Abstract

Purpose Claudins as the major components of tight junctions are important in maintaining cell–cell integrity and thus function as a barrier. Dysregulation of the claudins is often associated with loss of the epithelial phenotype, a process called epithelial–mesenchymal transition (EMT), which most often results in gain of migrative and invasive properties. However, the role of claudins in the endometrium or endometriosis has only rarely been examined. Methods In this study, we investigated localization of claudin-2 and claudin-3 in the eutopic and ectopic endometrium with immunohistochemistry. A detailed quantification with HSCORE was performed for claudin-2 and claudin-3 in endometrium without endometriosis and in cases with endometriosis compared to the three endometriotic entities: peritoneal, ovarian, and deep-infiltrating endometriosis. Results We found a preferential localization of both claudins in the glandular and the luminal epithelial cells in the endometrium with and without endometriosis. Quantification of localization of both claudins showed no differences in eutopic endometrium of control cases compared to cases with endometriosis. Furthermore, both claudins are localized highly similar in the ectopic compared to the eutopic endometrium, which is in clear contrast to previously published data for claudin-3. Conclusion From our results, we conclude that localization of claudin-2 and claudin-3 is highly stable in eutopic and ectopic endometrium without any loss of the epithelial phenotype and thus do not contribute to the pathogenesis of endometriosis.

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

“…Up to now, only four studies were published regarding claudin expression in endometriosis with their findings summarized in Table 3 . In contrast to one study showing cycle-dependent differences of mRNA expression of claudins [ 80 ], three studies found no differences in expression of claudins-2–4 and 11 [ 83 , 84 , 85 , 86 ]. Again, no significant differences between the eutopic endometrium of women with and without endometriosis could be shown for claudins-2–4, 7, and 11 ( Table 3 ).…”

“…Furthermore, the co-expression of epithelial and mesenchymal markers in the same cell or in a subset of cells remains to be clarified. In the case of a partial EMT in endometriosis, we observed a strong expression of cell–cell contacts in nearly all endometrial and endometriotic glands, as well as in nearly all epithelial cells [ 85 , 86 , 88 ], thus suggesting that the partial EMT might occur in the same cell(s).…”

“…In contrast to claudins-2, 5, 7, and 11, which are not significantly different in the ectopic endometrium compared to eutopic endometrium [ 83 , 84 , 85 , 86 ], claudin-1 and claudin-4 are significantly different, showing a decreased protein presence in peritoneal endometriosis [ 83 ]. Furthermore, claudin-4 was found to also be different in ovarian endometriosis [ 84 , 85 ] ( Table 3 ).…”

“…Furthermore, claudin-4 was found to also be different in ovarian endometriosis [ 84 , 85 ] ( Table 3 ). Instead, data for claudin-3 are controversial; whereas Pan et al [ 84 ] found a reduced protein presence in ovarian endometriosis, Hoerscher et al [ 86 ] did not identify any changes, but in contrast identified claudin-3 expression in nearly all glands in the ectopic endometrium.…”

“…We found that the cycles (25/28 = 89.3%) and hormonal treatments (13/28 = 46.4%) are often but not always reported. Furthermore, in eight reports [ 84 , 85 , 86 , 87 , 88 , 91 , 92 , 94 ], proliferative and secretory phases were compared. Thus, this review has some limitations; however, despite these shortcomings, several conclusions can be clearly drawn from the present investigation.…”