The WNT/β-catenin signaling pathway and expression of survival promoting genes in luteinized granulosa cells: Endometriosis as a paradigm for a dysregulated apoptosis pathway

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Abstract

Objective To analyze the WNT/β-catenin signaling pathway in luteinized granulosa cells from women with and without endometriosis in relation to cellular apoptosis. Design Basic. Setting University hospital. Patient(s) Patients with a laparoscopic diagnosis of endometriosis (n = 30) and women undergoing intracytoplasmic sperm injection for male infertility (control group n = 39). Intervention(s) Isolation of luteinized granulosa cells. Main Outcome Measure(s) Gene expression analysis of components of the WNT/β-catenin pathway, protein expression levels of β-catenin, and cell cycle studies in luteinized granulosa cells. Result(s) Compared with luteinized granulosa cells from control women, cells derived from endometriosis patients had significantly higher transcript levels of the β-catenin-independent molecules WNT4 and WNT5a and lower levels of the β-catenin-dependent molecule WNT1. A decrease of total β-catenin as well as of its dephosphorylated active form, together with an aberrant gene expression of the downstream targets survivin and BMP4, was detected in cells from affected women. Flow cytometry analysis confirmed an enhanced apoptosis of luteinized granulosa cells from patients with endometriosis. Conclusion(s) The concomitant dysregulation of specific members of the WNT pathway and of its pivot molecule β-catenin in granulosa cells characterized by an increased apoptosis suggests that the WNT/β-catenin signaling pathway might be involved in leading to granulosa cell atresia.

Original languageEnglish
Pages (from-to)1688-1696
Number of pages9
JournalFertility and Sterility
Volume101
Issue number6
DOIs
Publication statusPublished - 2014

Keywords

  • endometriosis
  • luteinized granulosa cells
  • WNT signalling
  • β-catenin

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine

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