Decreased Level of Neurotrophic Factor Neuritin 1 in Women with Ovarian Endometriosis after Receiving Gonadotropin-Releasing Hormone Agonist Treatment.

Endah Rahmawati,Pawan Kumar Maurya,Chii-Ruey Tzeng,Huei-Wen Chen,Wei-Chung Vivian Yang,Yen-Ping Lei

doi:10.3390/ijms20184352

Abstract

This study aimed to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the expression of neuritin 1 (NRN1) in women with ovarian endometriosis. We collected tissues and serum from women with endometriosis treated with (n = 45) or without (n = 37) GnRHa. NRN1 mRNA and protein levels were measured using qPCR and Western blot. Immunolocalization of NRN1 in endometriotic tissues was examined using immunohistochemistry. In addition, a follow-up study was carried out to monitor the serum level of NRN1 in patients before and after GnRHa treatment. Both mRNA (p = 0.046) and protein (p = 0.0155) levels of NRN1 were significantly lower in endometriotic tissues from patients receiving GnRHa treatment compared to the untreated group. Both epithelial and stromal cells of endometriotic tissues from untreated women with endometriosis exhibited stronger staining of NRN1 but not in those who were treated with GnRHa. The follow-up study showed that the serum level of the NRN1 concentration decreased significantly from 1149 ± 192.3 to 379.2 ± 80.16 pg/mL after GnRHa treatment (p = 0.0098). The expression of NRN1 was significantly lower in women with ovarian endometriosis treated with GnRHa. These results suggest that NRN1 may be a biomarker response to the effect of GnRHa treatment for patients with ovarian endometriosis.

Highlights

Endometriosis is defined as the presence of endometrial tissues and glands outside the uterine cavity [1]
Some evidence has revealed that nerve growth factor (NGF) and PGP9.5-immunoactive nerve fibers are expressed in ovarian endometriotic lesions and may be involved in the generation of pain in women with ovarian endometriosis [13,14,15,16]
Because gonadotropin-releasing hormone agonist (GnRHa) can induce amenorrhea, we assigned the phase of the menstrual cycle only in the GnRHa-untreated group

Summary

Introduction

Endometriosis is defined as the presence of endometrial tissues and glands outside the uterine cavity [1]. Most women with endometriosis suffer from ongoing pain and infertility [3]. These symptoms may be diminished by hormonal therapies that suppress estrogen production [4]. A gonadotropin-releasing hormone agonist (GnRHa) can be effective in relieving pain and improving the fertility potential of women with endometriosis [4]. Some studies have attempted to elucidate the role of nerve fibers in pain in women with endometriosis, but their direct relationship remains controversial. Some evidence has revealed that nerve growth factor (NGF) and PGP9.5-immunoactive nerve fibers are expressed in ovarian endometriotic lesions and may be involved in the generation of pain in women with ovarian endometriosis [13,14,15,16]

Objectives

Methods

Results