CONICET | Buscador de Institutos y Recursos Humanos

Although the etiology of endometriosis still remains unclear, a continuous effort is being done to elucidate its pathogenesis. Galectin-1 (Gal-1) is a β-galactoside-binding protein expressed in immune privileged sites which plays key roles in immune tolerance, tumor-immune escape and neovascularization. Nevertheless, the potential involvement of Gal-1 in endometriosis pathology has not yet been reported. Objective: To evaluate Gal-1 protein expression and histological location in human and mice endometriotic and endometrial tissue. Methods: Biopsies from endometriotic lesions (n= 12) and eutopic endometrium from premenopausal women with endometriosis (n= 5) and controls (n= 22) were taken during laparoscopy. Tissue samples were analyzed by Western blot (WB) and immunohistochemistry (IHC) to evaluate Gal-1 expression and distribution. Analyses by IHC were performed on primary cultures of ectopic endometriotic stromal cells and eutopic endometrial stromal and epithelial cells from patients and controls. In addition, ENDOMETRIOSIS was surgically induced in 8-week old female C57BL/6 mice (n= 7). After 4 weeks, animals were sacrificed and endometriotic-like lesions were removed. Paraffin sections were used to immunolocalize Gal-1 by IHC. Results: IHC assays revealed an abundant cytoplasmic expression of Gal-1 specifically confined to stromal and vascular cells from endometriosis lesions as well as in eutopic endometrium from patients and controls. However, we found no significant differences in the levels of Gal-1 expression assessed by WB among all groups studied (P > 0.05 ? Kruskal-Wallis test). A similar Gal-1 expression pattern was found in the endometrium and endometrioric-like lesions from endometriosis-induced in mice. Strikingly, we could not detect expression of this lectin in luminal or glandular epithelial cells in all groups analyzed. The same Gal-1 expression pattern in human primary endometrial cell cultures was found by IHC: the ectopic and eutopic endometrial stromal cells were positively immunostained, whereas the eutopic endometrial epithelial cells from patients and controls were found to be negative. Conclusions: To the best of our knowledge, this is the first study reporting strong expression of Gal-1 in endometriotic lesions and in eutopic endometrium from women with endometriosis and from endometriosis-induced mice. Interestingly, our results show that Gal-1 is only expressed in ectopic and eutopic stromal and vascular cells, but not in eutopic epithelial cells from patients and controls. These results support a potential role for Gal-1 in promoting the establishment and development of endometriosis. The higher expression of Gal-1 in the stroma and the vasculature of these tissues could act by favoring endometriotic cell proliferation, neovascularization of ectopic lesions and immune-escape, supporting its potential use as an emerging therapeutic target in endometriosis.