Nerve Fibres Detection in Paired Eutopic and Ectopic Endometria from Women with Endometriosis: Correlation with Nerve Growth Factor Expression

Sebastián Venegas,M Angélica Boric,Fernando Gabler,Reinaldo González-Ramos,M Cecilia Johnson,Edward Parada,Ariel Fuentes,Hugo Sovino

doi:10.4236/ojog.2015.57060

Abstract

Endometriosis, disorder characterized by the presence of endometrium outside the uterus cavity, is associated with chronic pelvic pain. Nerve growth factor (NGF) participates in development, repair and survival of neurons. We evaluated NGF and nerve fibres in eutopic and ectopic endometria from women with endometriosis and in normal endometrium from control patients without endometriosis. In endometrium collected during surgery for endometriosis (paired eutopic and ectopic endometria, proliferative n = 6 and secretory n = 7 phases) or during tubal ligation or hysterectomy for no endometrial disease (control, proliferative n = 6 and secretory n = 6 phases), NGF and neurofilament (NF) of nerve fibres were studied by immunohistochemistry measuring integrated optical density (IOD). Cytoplasmic NGF was detected in glands and stroma in all control, eutopic and ectopic endometrial samples; no statistical differences were found throughout the menstrual cycle. However, total (gland plus stroma) NGF IOD was higher in eutopic than in ectopic endometria during the secretory phase. NF was detected only in ectopic endometrium being eutopic and control endometria negative to this antibody, and no differences were observed between proliferative and secretory phases. Negative and significant correlation was found between NGF and NF expression in ectopic endometria only during the secretory phase. In conclusion, our results show a significant negative correlation between NGF and myelinated nerve fibres in secretory ectopic endometria. NGF expression was not significantly modified throughout the menstrual cycle in control and in endometriosis, even higher in eutopic than in ectopic tissues; the NGF secretion from lesions to pelvic cavity cannot be ruled out, and could explain the negative correlation observed. Although NF and NGF are not useful as diagnostic markers for endometriosis, their expression may be related to endometrial physiology and pathophysiology of the disease.

Highlights

Endometriosis is a gynaecologic disorder characterized by the presence of endometrial tissue outside the uterus cavity denominated as ectopic endometrium
Nerve growth factor (NGF) was strongly expressed throughout the menstrual cycle as a heterogeneous staining with small granulations in the gland and stromal cytoplasm of endometrium from control women (Figure 1(A) and Figure 1(B)), and from endometriosis women: eutopic endometrium (Figure 1(D) and Figure 1(E)) and ectopic endometrium in ovary (Figure 1(G) and Figure 1(H)), in peritoneum (Figure 1(J)), in rectovaginal septum as nodules (RVN) (Figure 1(K)) and in inflammatory cells morphologically indentified as macrophages localized in ovarian, uterosacral ligaments and peritoneal lesions (Figure 1(M), Figure 1(N) and Figure 1(O))
When the total positive NGF staining was analyzed, the integrated optical density (IOD) in eutopic endometrium was significantly higher than ectopic endometrium during the secretory phase (Figure 2(C))

Summary

Introduction

Endometriosis is a gynaecologic disorder characterized by the presence of endometrial tissue outside the uterus cavity denominated as ectopic endometrium. Dysmenorrhea, dyspareunia, dyschezia and chronic pelvic pain are frequent and produced by unknown mechanisms. The inflammatory condition is a consequence of the synthesis and release of several proinflammatory mediators from endometriotic lesions and immune cells to peritoneal fluid in the pelvic cavity and participates on pain and infertility associated to endometriosis [5] [6]. The high macrophage concentration reported in the peritoneal fluid from these patients is related with the increased nerve fibres density in the endometriotic lesions which are activated by the pro-inflammatory molecules secreted by the same macrophages [7] [8]

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