Estradiol promotes cells invasion by activating β-catenin signaling pathway in endometriosis.

Wenqian Xiong,Yi Liu,Lan Yu,Yicun Man,Ling Zhang,Hengwei Liu,Wei Xie,Yao Xiong

doi:10.1530/rep-15-0371

Abstract

Endometriosis is an estrogen-dependent disease that involves the adhesion, invasion, and angiogenesis of endometrial tissues outside of the uterine cavity. We hypothesized that a link exists between estrogen and beta-catenin (β-catenin) signaling in the pathogenesis of endometriosis. Human endometrial stromal cells (HESCs) were separated from eutopic endometrial tissues that were obtained from patients with endometriosis. β-catenin expression and cells invasiveness ability were up-regulated by 17β-estradiol (E2) in an estrogen receptor (ESR)-dependent manner, whereas β-catenin siRNA abrogated this phenomenon. Moreover, co-immunoprecipitation and dual immunofluorescence studies confirmed ESR1, β-catenin, and lymphoid enhancer factor 1/T cell factor 3 co-localization in the nucleus in HESCs after E2 treatment. To determine the role of β-catenin signaling in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium from endometriosis patients into ovariectomized severe combined immunodeficiency mice. The implantation of the endometrium was suppressed by β-catenin siRNA. Collectively, studies regarding β-catenin signaling are critical for improving our understanding of the pathogenesis of estrogen-induced endometriosis, which can translate into the development of treatments and therapeutic strategies for endometriosis.

Highlights

Endometriosis is a common benign gynecological disease that is defined as the presence of endometrial tissue outside the uterine cavity
The aims of the present study were to investigate the molecular mechanism underlying the interaction between estrogen and b-catenin signaling in human endometrial stromal cells (HESCs), illustrate whether the b-catenin signaling pathway plays a critical role in estrogen-facilitated invasion and angiogenesis by Human endometrial stromal cells (HESCs), and determine the role of b-catenin in a nonobese diabetic severe combined immunodeficiency (NOD–SCID) mouse endometriosis model
Abnormal b-catenin protein expression has been identified in ovarian endometrioid adenocarcinoma associated with endometriosis (Stewart et al 2013), and E2 has been shown to stabilize b-catenin expression through estrogen receptor binding in neuronal cells (Varea et al 2009)

Summary

Introduction

Endometriosis is a common benign gynecological disease that is defined as the presence of endometrial tissue outside the uterine cavity. This disease affects women of reproductive age and causes pelvic pain and infertility. The incidence rate of endometriosis is w10% (Giudice & Kao 2004). The pathogenesis of endometriosis is multifactorial, and endogenous and exogenous estrogens play key roles in its development and progression (Huhtinen et al 2012). The inhibition of systemic estrogen action is the current medical therapy for endometriosis and results in restricted proliferation. Aberrant production of estrogen plays an indispensable role in the pathogenesis of this disease

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