The Wnt/beta-catenin signaling in endometriosis, the expression of total and active forms of beta-catenin, total and inactive forms of glycogen synthase kinase-3 beta, WNT7a and DICKKOPF-1

Abstract

Objectives: The cyclical changes in proliferation and differentiation of endometrial cells are regulated by estrogen and progesterone via modulating Wnt/beta-catenin signaling. Imbalance in the expression of estrogen and progesterone receptors causes progesterone resistance in endometriosis patients. The aim of this study was to investigate the expression of some main components of Wnt/beta-catenin signaling including WNT7a, DKK-1, beta-catenin, and GSK-3 beta in eutopic endometrium and peritoneal endometriotic lesions of endometriosis patients compared to healthy endometrium in the mid-secretory phase of menstrual cycle. Study Design: This prospective study was performed, during a 12 months period from December 2015 to November 2016, on healthy women as the control group (n = 14) and endometriosis patients (n = 34). We used real-time polymerase chain reaction and Western blot techniques. Results: Protein and mRNA expression of DKK-1 were significantly down-regulated in both endometriotic lesions and eutopic endometrium of endometriosis group. We also demonstrated that the expression of non-phosphorylated beta-catenin (active form) and phosphorylated GSK-3 beta (inactive form) were up regulated in endometriosis patients. The mRNA levels of beta-catenin, GSK-3 beta, and WNT7a, as well as the protein levels of total p-catenin, total GSK-3 beta, and WNT7a in endometriosis group, were not significantly different with those in control group. The patterns of mRNA and protein expression of all interested factors in the lesions were similar to those in the eutopic endometrium of same patients. Conclusions: It seems that the aberrant activation of Wnt/beta-catenin signaling in the secretory phase of the menstrual cycle in endometriosis has two essential elements: excessive inactivation of GSK-3 beta and suppression of the expression of Wnt signaling inhibitor DKK-1. Interventions in this signaling pathway may allow for the exploration of potential new targets for the control of development and progression of endometriosis. (C) 2017 Elsevier B.V. All rights reserved.