Theories on the pathogenesis of endometriosis (original) (raw)
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The putative role of cell adhesion molecules in endometriosis: can we learn from tumour metastasis?
Molecular Medicine Today, 1999
20% of women in their reproductive life span 1. The endometriotic tissue often undergoes cyclic proliferation and breakdown similar to eutopic endometrium, resulting in local inflammatory reactions. These processes cause the cyclical character of endometriosis with dysmenorrhea, dyspareunia, pelvic pain, catamenial hematuria and other symptoms derived from the affected organ (see Box 1). Moreover, up to 50% of infertile patients have this disease 2. Thus, although not malignant, endometriosis causes significant physical pathology in affected women, as well as causing psychological and social problems. Considering this and the frequency of endometriosis, it is stunning how little research effort has been put into understanding the molecular basis of this important disease. Currently, it is postulated that the majority of endometriotic lesions are derived from viable eutopic endometrial cells that are transported to the peritoneal cavity by retrograde menstruation, which then adhere to the peritoneal wall, proliferate and form endometriotic lesions (the implantation theory 3). Retrograde menstruation occurs in almost all women and can be a continuous cellular source for the maintenance of endometriosis 4. A second possibility is that endometriosis is established, at least in some cases, by sex hormone-dependent transformation of peritoneal cells into Müllerian-type epithelium (the metaplasia theory 5). The implantation theory is supported by: (1) the observation that viable endometrial cells have the capacity to implant; (2) by the predominant localization of implants in the lower pelvis; and (3) by experiments in which endometrium has been transplanted into nude mice. The metaplasia theory provides an explanation for the ENDOMETRIOSIS is an invasive but benign gynaecological disease that is characterized histologically by the presence of endometrial-like tissue (glandular epithelium and stroma) outside the uterine cavity. It 304
Reduced proliferation and cell adhesion in endometriosis
Molecular Human Reproduction, 2000
lium, the presence of the adhesion complex E-cadherin with the associated α- and β-catenin was investigated. Specimens of endometrium in the proliferative phase of 36 patients without, and 79 patients with, endometriosis together with endometriotic lesions were studied. The study revealed a significantly reduced proliferation activity in uterine epithelium within the ectopic lesions but no differences between eutopic endometria of
Early-stage endometriosis: adhesion and growth of human menstrual endometrium in nude mice
Fertility and Sterility, 2000
To evaluate the implantation of menstrual endometrium and the early stages of evolution of endometriotic lesions. Experimental prospective study. An academic research environment. Ten nude mice. A minilaparotomy was performed to place fresh human menstrual endometrial samples in the peritoneal cavity. Removal of the transplants was performed successively on days 1, 3, and 5 by laparotomy. Adhesion of endometrial fragments and early stages of endometrial lesions was morphologically and immunohistochemically studied. As early as day 1, stromal cells were found to be attached to the mesothelium. A progressive reorganization of epithelial and stromal cells into endometrial glands was observed. On day 5, cystic endometriotic lesions were characterized by more extensive proliferative activity in glandular cells and a higher VEGF score in stromal cells than that observed in previously removed transplants. Menstrual human endometrium is able to implant on intact mesothelium and to reorganize itself into structured glands and stroma under the influence of unknown factors. We suggest that stromal and glandular cells have two distinct roles: stromal cells are involved in the attachment process and glandular cells in the growth of the endometriotic lesion.
Expression pattern of integrin adhesion molecules in endometriosis and human endometrium
Human Reproduction Update, 1998
Introduction 710 Analyses of endometrial samples for integrins 711 Integrin expression in endometrial and endometriotic samples 713 Conclusions 716 References 717 Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins α v , α 2 β 1 , α 3 β 1 , α 3 , α 6 , β 1 , β 2 and β 3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin α 6 was expressed in all endometriotic and endometrium samples. The integrin α 3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin β 3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferen-tiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum.
New considerations for the pathogenesis of endometriosis
International Journal of Gynecology & Obstetrics, 2002
Objecti¨es: To review the available evidence regarding the immunological, epidemiological and other factors involved in the pathogenesis of endometriosis. Methods: Literature review. Results: Endometriosis remains a poorly-understood disease of unknown etiology and pathogenesis. Conclusions: There is evidence to suggest that alterations in the immune response, whether genetically transmitted or environmentally induced, predispose women to the ectopic implantation of endometrial cells transported into the peritoneal cavity by way of retrograde menstruation. This predisposition may exist because of an impaired peritoneal clearing of endometrial cells and fragments or because of pathological angiogenesis. ᮊ 2002 International Federation of Gynecology and Obstetrics.
Human Reproduction, 2007
BACKGROUND: Endometriosis, classified as the presence of endometrial cells in ectopic sites, is a debilitating disease causing pain and infertility in 10% of women of reproductive age. It is associated with the aberrant expression of extracellular matrix (ECM) components and their receptors, integrins. METHODS: We analysed the expression of integrins in stromal cells derived from peritoneal, ovarian and deeply infiltrating endometriotic lesions and from endometrium from women with and without endometriosis in vitro, using quantitative immunocytochemistry. The adhesive and proliferative capacity of each of the cell types in response to ECM components was assessed by in vitro assays of cell attachment and DNA synthesis. RESULTS: We demonstrate that eutopic and ectopic endometrial stromal cells from women with endometriosis exhibit an aberrant integrin profile in vitro compared with stromal cells derived from healthy controls. In addition, the former display increased adhesion and proliferative capacity in response to specific ECM components. CONCLUSIONS: We propose that the increased adhesive and proliferative potential of cells from endometriotic lesions may be a key feature in the pathogenesis of endometriosis. Furthermore, the elevated responsiveness of eutopic cells from women with endometriosis may contribute to the predisposition of some women to the disease.
Pathogenesis of Early-Onset Endometriosis
2015
Three main theories have been put forward to explain the pathogenesis of endometriosis, that of a retrograde menstrual transplantation, that of an induction of endometrial cells, and that of an in situ development. These hypotheses belong to two main groups: those proposing that implants originate from the endometrium and those advocating an origin from extra-uterine tissues. More recently, the discovery that stem/progenitor cells from bone marrow can differentiate into endometrial cells suggests a novel pathway through which these cells may colonize peritoneal and extra-peritoneal organs and differentiate into ectopic endometrium. On the other hand, for early-onset endometriosis a different pathogenetic mechanism may be in place. The possibility exists that in neonates endometrial cells and stroma are retrogradely disseminated in the pelvis, thanks to the presence of uterine bleeding, either visible or occult. Since menstrual desquamation causing neonatal bleeding may contain endometrial stem cells, they may in turn be responsible, through a variety of mechanisms, for early onset endometriosis.