Increased Circulating MMP-2 Levels in Infertile Patients With Moderate and Severe Pelvic Endometriosis

Abstract

The current study compares the levels of matrix metalloproteinase (MMP)-2 and MMP-9 in the follicular fluid (FF) of infertile patients with and without endometriosis submitted to ovarian stimulation for in vitro fertilization and the levels of MMP-2 in the serum of the same patients. We also evaluated whether the severity of endometriosis can influence serum and/or FF concentration of these metalloproteinases. A cross-sectional study was conducted on 30 patients: stage I/II endometriosis (n = 10), stage III/IV endometriosis (n = 10), and control (infertility due to tubal and/or male factor; n = 10). Blood samples for the analysis of MMP-2 levels were obtained during the early follicular phase of the menstrual cycle. The FF samples for the analysis of MMP-2 and MMP-9 were obtained on the day of oocyte retrieval. The concentrations of MMP-2 and MMP-9 were determined by zymography. No intragroup or intergroup difference was observed in MMP-2 or MMP-9 levels in FF. Significantly higher MMP-2 levels were detected in the serum of infertile women with stage III/IV endometriosis compared to women with stage I/II endometriosis. In conclusion, no differences were observed in the follicular levels of MMP-2 and MMP-9 between infertile patients with and without endometriosis. However, the levels of MMP-2 were significantly higher in the serum of infertile women with advanced stages of endometriosis. Taken together, the present results demonstrate that advanced pelvic endometriosis severity is related to higher serum MMP-2 levels but does not influence follicular MMP-2 or MMP-9 levels in periovulatory follicles obtained from stimulated cycles.

The plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 are elevated in patients with endometriosis

“…It can possibly be attributed to two reasons: (1) greater tissue remodeling that may occur with disease progression, with a consequent higher local and systemically identifiable MMP-9 activity; (2) the inflammatory microenvironment in ectopic tissue may increase the production of MMP-9, which in turn facilitates invasion and progression of the disease, being positively correlated with the severity of endometriosis. 21 In a recent study by Malvezzi et al, 19 the authors compared the concentrations of MMP-2 and MMP-9 in the FF of infertile females with or without endometriosis; no difference was observed in MMP-2 or MMP-9 concentrations in FF among females with or without endometriosis or at different stage of endometriosis; however, significantly higher MMP-2 concentrations were detected in the serum of females with stage III/ IV endometriosis compared to those with stage I/II endometriosis, which is consistent with our results. The data regarding the quantification of MMP-9 in serum were not presented in their study.…”

“…Extensive investigations in serum/plasma, urine, peritoneal fluid (PF) and/or follicular fluid (FF) biomarkers for endometriosis have been carried out in females with endometriosis, 18 including measurement of MMP-2 activity in FF and serum 19 ; however, there have been no detailed data on the association of circulating and PF concentrations of MMP-9 with disease severity of endometriosis thus far. The present study aimed to determine the MMP-9 concentrations in plasma and PF of females with endometriosis and to correlate concentrations of MMP-9 with severity of disease.…”

The Role of Matrix Metalloproteinase2 (MMP2) in Serum and Peritoneal Fluid of Endometriotic Patients

“…The results are consistent with research Malvezzi et al, also found elevated levels of MMP-2 serum of infertile women with stage III-IV higher than stage I-II. 15 Pathogenesis of endometriosis regarding attachment scheme-aggression-angiogenesis (AAA) has been accepted. In this process, the role of MMP uncontested.…”

“…Increased circulation of MMP-2 in patients with severe pelvic endometriosis through the mechanism of major tissue remodeling happened due to disease progression, as a result of increased activity of MMP-2 systemic and local, as well as the high activity of ectopic aromatase tissues can increase the production of MMP-2, which can facilitate the invasion and progression of the disease, so that MMP-2 correlated with increasing degrees of endometriosis. 15…”

Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

“…"Recently Malvezzi et al reported that the level of MMP2 is significantly higher in serum of infertile women with advanced stages of endometriosis (29)". "Pelch et al also showed that the expression of genes associated with the extracellular matrix, cell adhesions, immune function, cell growth, and angiogenesis are altered in the endometriotic lesion compared to the eutopic uterus (13)".…”