Role In Pathogenesis Of Endometriosis Research Articles

Angiogenic activity and IL-8 concentrations in peritoneal fluid and sera in endometriosis

Objectives: During menstruation endometrial fragments are transported into the peritoneal cavity where they form endometriotic lesions. Angiogenesis is proposed as one of the mechanisms in endometriosis pathogenesis. The aim of the study was to determine the angiogenic activity and interleukin 8 concentrations in peritoneal fluid and sera in endometriosis. Methods: Angiogenesis was determined in cutaneous assay in Balb/c mice; IL-8 concentrations were measured by ELISA test in sera and peritoneal fluid of 32 control and 56 endometriosis patients. Wilcoxon and Mann–Whitney tests and Spearman rank correlations were used in statistical analysis. Results: Peritoneal fluid and sera from the examined group had higher angiogenic activity and interleukin 8 concentrations. There was correlation found between AFS and neovascularization induced by sera and PF of patients with peritoneal lesions. Conclusions: Angiogenesis plays an important role in pathogenesis of endometriosis. Although IL-8 takes part in neovascularization, there are other factors modulating angiogenesis in endometriosis.

Shed Endometrium in Menstrual Fluid Obtained from Fertile Women Without Endometriosis Can Adhere to and Invade the Epithelium

Objectives: The nature of adhesion, implantation and invasion of the endometrial cells into peritoneum still remains to be elucidated and it is unknown which factor, endometrial or peritoneal, play a major role in pathogenesis of endometriosis. Furthermore, it is still controversial whether or not the shed endometrium (SE) obtained from menstrual fluid (MF) can adhere to and invade intact epithelium. Therefore, the purposes of this study were to observe the adhesion sites of SE on intact epithelium using amnion, and to evaluate morphological changes by duration of in-vitro culture and access the process of adhesion and invasion of SE. Design: Immunohistochemical (IHS) and ultrastructural observation of the adhesion sites. Materials and Methods: The MFs were collected from five fertile women who had regular menstruation on the second or third day of the menstrual period, using Wallace catheter. None of them had endometriosis lesions in their pelvic cavity under the diagnostic laparoscopy. The fresh amnion was obtained from term placenta delivered without any complication. The SE in each MF was collected by filtering and were placed on amniotic epithelium (AE) and cultured for 1,3,5 or 7 days. The adhesion sites of SE were observed under a stereomicroscope and prepared for IHS and electron-microscopic observations. Results: After 1 day of culture, adhesion sites of SE were observed but most of them were detached during preparation for histology. After 3 days of culture, the endometrial epithelial cells (EEC) were shown to adhere to the amniotic epithelial cells (AEC) and the endometrial stromal cells (ESC) penetrated through the intercellular junction of AEC. After 5 days of culture, the endometrial fragment composed with EEC and ESC was demonstrated to adhere tightly to AE and basement membrane (BM). At mid portion of the adhesion site, the continuity of BM was lost and through this broken portion, some ESC invaded into extracellular matrix (ECM). After 7 days of culture, the adhered EECs were shown to spread out along the BM and detach the AE from BM. According to spreading of EEC, the endometrial stroma located inside of endometrial fragment was in contact with BM and ECM, and a large number of ESC were invading. The endometrial cells were characterized by IHS staining with cytokeratin and vimentin. MMP-2 was expressed in the endometrial stroma and strongly expressed at the invading portion. Conclusion: The shed endometrium in MF could adhere to and invade the epithelium, even though it was obtained from fertile women without endometriosis. This process could be described the sequence of three steps (attachment, degradation and invasion), and might be similar to tumor cell invasion. MMP-2 expressed in ESC may play a role in this process.

Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells.

Interleukin-8 (IL-8) is a chemoattractant and activating factor for human neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with endometriosis has been shown to have increased neutrophil chemotactic activity. We postulate that IL-8 may be an important modulator in the pathogenesis of endometriosis and adhesion formation. We first investigated IL-8 concentrations in the peritoneal fluid of women with or without endometriosis, then assessed peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1 pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1 alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml) for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1 alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time-dependent manner. Non-treated mesothelial cells in culture also produced and secreted IL-8 protein quantified by ELISA, but again higher concentrations were induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8 concentrations were elevated in peritoneal fluids from women with endometriosis. Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL-8 protein. The regulated expression of this angiogenic factor may play a role in pathogenesis of endometriosis.

Altered maturation and function of peritoneal macrophages: Possible role in pathogenesis of endometriosis

Human peritoneal macrophages from healthy women and patients with endometriosis were analyzed with flow cytometry for size distribution, cell membrane antigen expression, and membrane function. Endometriosis was associated with a significantly increased number of peritoneal macrophages and a higher proportion of large macrophages with increased expression of three antigen markers. Peritoneal macrophages from normal patients exhibited diminished cell membrane capping function as compared with that of endometriosis-related macrophages or blood monocytes. On the basis of these findings, a hypothesis is formulated suggesting that endometriosis is associated with an increased influx of macrophages that are allowed to undergo further maturation-activation. The resultant population of large macrophages may contribute to the maintenance of the disease or associated infertility.