The Expression And Intracellular Distribution Of Ezrin And Cytoskeleton In Endometriosis

Background:Endometriosis is a disorder defined as the presence of viable endometrial glands and stroma outside the uterine endometrium and myometrium. The common pathological manifestations are cyclic hemorrhage in the invasion sites and local organization and adhesion around long-time lesions. The common clinical manifestations include dysmenorrhea, infertility, pelvic adhesions, and other clinical manifestations, due to ureter, lung and other distant metastasises, can also occur. According to different population studied, the prevalence of endometriosis ranges from2to22percent in asymptomatic women[1-3], from20to50percent in infertile women[4] and40to50percent in those with pelvic pain[5-7].As a benign disorder, endometriosis has some characteristics of malignant tumor, such as invasion, recurrence and metastasis, and is threatening many women’s health and life quanlity. Although surgeries and drugs are adopted in clinical therapy, but the recurrence rate is still reach up to about20to50percent[8-9]. The pathogenesis of endometriosis is still unclear. A variety of theories have been proposed, including retrograde transplantation theory, hematogenic and lymphogenic spread, metaplasia of coelomic epithelium and induction theory. However, no theory can explain all the mechanisms of endometriosis. The implantation hypothesis of Sampson is widely accepted, but it has not demonstrated how the endometrium leave the original place and finish the complex process that adhering-invasing-vascularizing outside the uterine cavity. Especially, it has not been demonstrated how exterior and interior signals cells received cause intra-celluler structure changes and subsequently lead to cell migration[10].Cytoskeleton, a set of racks making-up by fibriform structures, includes microfibril, microtubule and intermediate filament. The function of cytoskeleton is supporting and keeping cellular shape and moving. Many studies have shown that cytoskeleton and its bonding proteins are the material basis of cell migration and a lot of molecules participate the precise adjustment. It is found that invasion and metastasis of many malignant tumors are closely related with cytoskeleton. As one of the disorders characterized by invasion and distant metastasis, endometriosis occurs and develops with the change of cytoskeleton.Ezrin, as a linkage protein between membrane and cytoskeleton, is a member of the ezrin-radixin-moesin (ERM) protein family. It is usually distributed submembrane and in microvilli, filar pseudopodia and cellular crease. Its effect on adhesion and migration of tumor cell is increasingly becoming clear recent years and more and more attention has been located to its correlation with gynecologic diseases. We presume that ezrin, as a membrane-cytoskeleton linkage protein, may participate in cell migration and develop important effect in the occurrence, development and recurrence of endometriosis.In this study, we checked the expression and location of ezrin, microfibril and microtubule in endometriosis by immunofluorescence and laser confocal microscope, analysed the change of those proteins by fluorescence intensity semiquantitative test, and subsequently seek the possible mechanisms of invasion in endometriosis. Objective:To check the expression and location of ezrin, microfibril and microtubule in endometriosis and subsequently seek the subcellular mechanisms of endometriosis. Methods:We checked the expression and location of ezrin, microfibril and microtubule of endometrial cells from women with or without endometriosis by immunofluorescence and laser confocal microscope, analysed the change of those proteins by fluorescence intensity semiquantitative test. Results:1. Ezrin is usually distributed in the cortex of glandular epithelium and slightly in the cytoplasm or stroma; microfibril and microtubule are attributed directionally in cells;2. Ezrin is dispersedly distributed both in stroma and glandular epithelium cells of endometriotic tissue; significantly higher expression of ezrin had been found in the stroma of endometriotic tissue than both the homologous eutopic endometrium and endometrium from healthy controls (P<0.05), while no significant difference had been found in the glandular epithelium(P>0.05); there was no significant difference in ezrin expression between the eutopic and normal endometrium both in stroma and glandular epithelium (P>0.05).3. Microfibril is dispersedly distributed both in stroma and glandular epithelium cells of endometriotic tissue; significantly higher expression of actin had been found in the stroma of endometriotic tissue than the homologous eutopic endometrium and endometrium from healthy controls (P<0.05), while opposite result had been found in the glandular epithelium (P<0.05); there was no significant difference of actin expression between the eutopic and normal endometrium both in stroma and glandular epithelium (P>0.05)4. The cilium of glandular epithelium cells is shorter in ectopic tissue; no significant difference of tubulin expression had been found among three groups (P>0.05). Conclusions:1. Cell migration and implantation in the endometriosis are accompanied with cytoskeleton reconstructions.2. Ezrin is involved in the occurrence of endometriosis and cytoskeleton reconstructions of endometriosis.3. Stroma cells play an important role in the process of cell migration and invasion in endometriosis; ectopic glandular epithelium may be generated from mesenchymal epithelial transition.