Differential expression of CRH, UCN, CRHR1 and CRHR2 in eutopic and ectopic endometrium of women with endometriosis.

Aikaterini Vergetaki,Hilary Od Critchley,Eirini Taliouri,Evangelia A Papakonstanti,Luca Sabatini,Antonis Makrigiannakis,Udo Jeschke,Thomas Vrekoussis

doi:10.1371/journal.pone.0062313

Aikaterini Vergetaki, Hilary Od Critchley + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0062313

Copy DOI

Abstract

Endometriosis is considered as a benign aseptic inflammatory disease, characterised by the presence of ectopic endometrium-like tissue. Its symptoms (mostly pain and infertility) are reported as constant stressors. Corticotropin releasing hormone (CRH) and urocortin (UCN) are neuropeptides, strongly related to stress and inflammation. The effects of CRH and UCN are mediated through CRHR1 and CRHR2 receptors which are implicated in several reproductive functions acting as inflammatory components. However, the involvement of these molecules to endometriosis remains unknown. The aim of this study was to examine the expression of CRHR1 and CRHR2 in endometriotic sites and to compare the expression of CRHR1 and CRHR2 in eutopic endometrium of endometriotic women to that of healthy women. We further compared the expression of CRH, UCN, CRHR1 and CRHR2 in ectopic endometrium to that in eutopic endometrium of women with endometriosis. Endometrial biopsy specimens were taken from healthy women (10 patients) and endometrial and endometriotic biopsy specimens were taken from women with endometriosis (16 patients). Τhe expression of CRH, UCN, CRHR1, and CRHR2 was tested via RT-PCR, immunohistochemistry and Western blotting. This study shows for the first time that CRH and UCN receptor subtypes CRHR1β and CRHR2α are expressed in endometriotic sites and that they are more strongly expressed (p<0.01) in eutopic endometrium of women with endometriosis compared to healthy women endometrium at the mRNA and protein level. CRH, UCN, CRHR1 and CRHR2 mRNA were also more highly expressed in ectopic rather than eutopic endometrium (CRH, UCN, CRHR2α: p<0.01, CRHR1β: p<0.05) and protein (CRH and UCN: p<0.05, CRHR1 and CRHR2: p<0.01) in women with endometriosis. These data indicate that CRH and UCN might play an immunoregulatory role in endometriotic sites by affecting reproductive functions such as decidualization and implantation of women with endometriosis.

Highlights

Endometriosis is one of the most important benign chronic diseases affecting the 6–10% of women of reproductive age, being mainly associated with pelvic pain, adhesion formation and infertility
In order to verify the expression of the Corticotropin releasing hormone (CRH), UCN, CRHR1 and CRHR2 in endometriotic lesions, we firstly tested the expression of these transcripts by RT-PCR
We show that CRH, UCN, CRHR1, CRHR2 and the receptor subtypes CRHR1b and CRHR2a are expressed in endometrium and endometriotic sites at mRNA and protein level

Summary

Introduction

Endometriosis is one of the most important benign chronic diseases affecting the 6–10% of women of reproductive age, being mainly associated with pelvic pain, adhesion formation and infertility. The expression and function of CRH and UCN have been found to be impaired in eutopic endometrium of women with endometriosis [26]. These data suggest a crucial role of CRH and UCN in pathogenesis of endometriosis. The relative expression of CRH, UCN and their receptors in eutopic and ectopic endometrium of endometriotic women and in eutopic endometrium of healthy women and women with endometriosis has never been investigated. We have investigated the relative expression levels of these molecules in eutopic and ectopic endometrium of endometriotic and healthy women providing the first evidence for a potential role of CRH receptors in infertility profile of endometriotic women

Objectives

Methods

Results

Conclusion