The role of the peritoneum in the pathogenesis of endometriosis

Abstract

BACKGROUND Endometriosis affects 6-10% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhoea, dyspareunia and infertility. Endometriosis is defined by the presence of endometrial tissue outside the uterus, most commonly attached to the pelvic peritoneum. The endometrium in women with endometriosis is reported to be altered and there is increasing evidence that the phenotype of the pelvic peritoneum may also play a role in the establishment and maintenance of the disease. The aim of this review is to discuss the putative role of the pelvic peritoneum in the pathophysiology of peritoneal endometriosis. METHODS A review was undertaken of the published literature on (i) the anatomy and physiology of the peritoneum and (ii) the potential roles played by peritoneal cells in the establishment and maintenance of peritoneal endometriosis. The current understanding of the biology of peritoneal endometriosis is summarized and the potential interaction of the peritoneum with ectopic endometrial cells in endometriosis is highlighted. RESULTS Several studies indicate that differential expression of peritoneal mesothelial adhesion factors occurs in women with endometriosis, providing potential ectopic endometrial cell attachment sites for the establishment of endometriosis lesions. Changes in the peritoneal mesothelial cell phenotype, including loss of tight junctions, may allow ectopic cells to bind to, or early lesions to invade into, the extracellular matrix. Epithelial-to-mesenchymal transition of peritoneal mesothelial cells may also lead to an increase in lesion invasion and formation of fibrotic tissue in and around the lesion. There is evidence that the peritoneal mesothelium may also play a role in the invasion potential of ectopic cells by production of MMPs increasing local tissue remodelling. Peritoneal immune scavenging function may be lowered in women with endometriosis; for example there is a notable increase in macrophage-derived secretion products in women with endometriosis associated with increases in cell proliferation, cell adhesion and neovascularization. CONCLUSIONS The pelvic peritoneum appears to play a key role in the development and maintenance of endometriosis.

Changes in the coelomic microclimate during carbon dioxide laparoscopy: morphological and functional implications

“…As it passes the throttle valve on the cylinder head the CO 2 vaporizes, expands and cools as a result of the Joule-Thomson effect. When it enters the coelom via the gas insufflator, the relative humidity of introduced dry CO 2 gas is 0.0002 % [5], with a temperature of 20°C and a high velocity [2,5,9]. The use of cold-dry CO 2 gas causes a number of local effects on the peritoneal mesothelium, as well as systemic effects in the subject [5].…”

“…PMCs secrete matrix metalloproteases (MMP) which digest collagens and remodel the ECM. This is regulated by TGF-β and is crucial in adhesion formation and endometriosis or cancer cell invasion of the ECM [9,14]. The PMC thus control fluid and cell transport, initiation and resolution of inflammation, leucocyte migration, tissue repair, lysis of fibrin deposits preventing adhesion formation, protection against invading microorganisms and, possibly, tumour dissemination in the coelomic cavity [8].…”

“…IL-6 correlates with the severity of peritoneal damage or onset of major postoperative complications [49]. The dysregulated repair mechanisms that mediate adhesions after laparoscopic and open surgery may also promote cellular activation, such as peritoneal metastasis and endometriosis [9,18,49,[67][68][69][70][71][72][73][74].…”

“…These include loss of E-cadherin and expression of N-cadherin, loss of tight junctions, expression of mesenchymal markers: fibronectin, vimentin, fibroblast specific protein-1(FSP-1), smooth muscle actin (α-SMA) with associated increased cellular polarity and migration [9]. MMT and EMT are induced by HIF, TGF-β and repression of E-cadherin.…”

Estradiol-mediated hepatocyte growth factor is involved in the implantation of endometriotic cells via the mesothelial-to-mesenchymal transition in the peritoneum

“…Recent studies suggest that the phenotype of the pelvic peritoneum plays a part in the establishment and persistence of endometriosis (3,37); however, little is known about how the peritoneum is affected by and related to the progression of endometriosis under the influence of estradiol.…”