Paracrine changes in the peritoneal environment of women with endometriosis

Abstract

During the past decade, macrophage-derived substances such as prostanoids, cytokines, growth factors and angiogenic factors have been detected in the peritoneal fluid of women with endometriosis. In particular, growth-promoting and angiogenic factors are considered to be substantially involved in the pathogenesis of endometriosis. In this study, vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β) and intercellular adhesion molecule 1 (ICAM-1), substances recently detected in the peritoneal fluid of women with endometriosis, were assessed with regard to their concentrations in different stages of endometriosis and changes of the peritoneal paracrine activity after medical treatment with a gonadotrophin releasing hormone agonist (GnRHa). Peritoneal fluid was obtained from patients with endometriosis during laparoscopy before and after a 4-month treatment with a GnRHa. VEGF, TGF-β and ICAM-1 could be detected in all women presenting with various stages of active endometriosis. After GnRHa therapy, all patients showed significant decreases in mean concentrations of VEGF (194 ± 77 pg/ml), TGF-β (902 ± 273 pg/ml) and ICAM-1 (157 ± 52 ng/ml). Patients with stage III and IV endometriosis (according to the rAFS score) had much higher concentrations of VEGF and TGF-β before treatment compared with those patients with mild endometriosis (rAFS stages I and II). The most striking decrease in concentration was for TGF-β, from 902 pg/ml before to 273 pg/ml after therapy. These results indicate an important role for paracrine activity in the establishment and maintenance of endometriosis. Indeed, treatment with a GnRHa may reduce paracrine activity in the peritoneal cavity via hypo-oestrogenism and provide proof of successful therapy.

Comparison of ovarian cancer markers in endometriosis favours HE4 over CA125

“…The present results confirm those of a previous study (40) demonstrating that GnRHa, administered for the reduction of pain (41), resulted in a significant reduction in peritoneal pro-inflammatory cytokine and growth factor levels, therefore mediating a regression in the inflammatory activity in the peritoneal environment in patients with endometriosis (42). The present study shows that several pro-inflammatory cytokines and growth markers exhibit reduced PF concentrations following GnRHa treatment in patients with endometriosis (42).…”

Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large?

“…VEGF gene expression and protein expression levels are elevated in endometriotic cells and peritoneal fluid macrophages [51,[228][229][230][231][232] . Similarly, the role of ICAM-1 in endometriosis has been well-documented and it is believed that it may be involved in the mechanism that can escape immunosurveillance and allow refluxed endometrial cells to spread and invade other locations [233] .…”

Association between MMP1 and MMP9 activities and ICAM1 cleavage induced by tumor necrosis factor in stromal cell cultures from eutopic endometria of women with endometriosis

“…Tumoral cells release this molecule, which conserves its binding capacity to the ITGAL antigen and competes with membrane-bound ICAM1, reducing the amount of leucocytes available for the recognition of surface ICAM1 on target cells and allowing the target cells to escape from leukocyte surveillance. In endometriosis, the concentration of sICAM1 released from endometrial cells and the augmented levels of this molecule in the peritoneal fluid show a direct and significant association with the inhibition of the cytotoxic activity of NK cells, the severity of endometriosis, and the type of endometriotic lesion (Somigliana et al 1996, Kupker et al 1998, Gonzalez-Ramos et al 2007.…”