Autophagy in Endometriosis: Beta-Catenin Suppressive Role

Popryadukhin, A. Y.; Asaturova, A. V.; Arakelyan, A. S.; Stepanian, A. A.; Adamyan, L. V.

Study Objective To evaluate the occurrence of the autophagic process in ovarian endometriomas (OE), rectocervical endometriosis (RE), adenomyosis (A), and peritoneal endometriosis (PE) compared with eutopic endometrium. Design Prospective cohort study, Level II-1. Setting National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation. Patients or Participants We recruited 120 patients with endometriosis and adenomyosis: 47 patients with (OE), 20 patients with (RE), 20 patients with (A), 33 patients with (PE). Interventions All patients had laparoscopic surgery performed in the proliferative non-menstrual phase of their menstrual cycle. Histological analysis was carried out according to a standard procedure. Immuno-histochemical analysis of ectopic and eutopic endometrium samples was carried out using the Tissue-Tek Quick-Ray kit, which allows for the preparation of paraffin blocks with a large number of tissue samples (tissue microarray). Antibodies to LAMP 1 (1:100), LC3 (1:50), bcl-2 (1:50), (Ventana, Roche) were used. Measurements and Main Results In patients with EO, RE, A and PE, we noticed a significant down-regulation of autophagy (LAMP1 and LC3 expression) and up-regulation of beta-catenin expression in ectopic endometrium compared with the eutopic endometrium of affected women (p<0.05). Our study did not demonstrate the difference in expression of tested markers among endometriosis lesions of different localizations (p>0.05). This data is consistent with our previous observation made on smaller number of patents, possibly confirming the data. Conclusion We hypothesized that there is a relationship between autophagy and wnt/signaling pathway regulation, demonstrating the inverse ratio between beta-catenin and autophagy-marker expression. Based on the results in this study, we can say with increased certainty that increased beta-catenin could suppress autophagy, supporting ectopic endometrium through anoikis and other types of apoptosis. So we can suppose that target-based therapy suppressing the wnt/beta-catenin pathway can activate autophagy in endometriosis and, pending clinical studies, become a part of target-based pre-surgical, intra-operative, an post-operative endometriosis therapy.