The role of the peritoneum in the pathogenesis of endometriosis (original) (raw)
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Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion
Fertility and Sterility, 1999
Objective: To determine whether whole fragments of endometrium can adhere to peritoneum with intact mesothelium. Design: Tissue culture and immunohistochemical study. Setting: University medical center. Patient(s): Reproductive-age women undergoing surgery for benign conditions. Intervention(s): Explants of human peritoneum from the anterior abdominal wall and the posterior surface of the uterus were cultured with whole fragments of mechanically dispersed endometrium. Main Outcome Measure(s): Adhesion of endometrial fragments to the surface of the peritoneum was evaluated. Adherent endometrium was identified with the use of the dissecting microscope and by the performance of serial sections of the peritoneum explants. Immunohistochemical staining of the mesothelium with antibodies to cytokeratin was used to ensure an intact layer of mesothelium beneath the endometrial implants. Transmission electron microscopy also was used to evaluate this adhesion process. Result(s): Endometrium was identified attached to the surface of the peritoneum. Most of the implants did not have identifiable mesothelium beneath them, but most had intact mesothelium running up to the point of attachment. Approximately 10% of the endometrial implants had intact mesothelium at the site of attachment. Endometrial stromal cells, and not epithelium, attached to the mesothelium. Conclusion(s): Endometrium can attach to the mesothelial surface of the peritoneum. Endometrial stromal cells are involved in this attachment. Invasion through the mesothelium seems to occur rapidly.
Endometriotic disease: the role of peritoneal fluid
Human Reproduction Update, 1998
Introduction 741 Peritoneal fluid: a specific microenvironment 742 The intraovarian milieu 744 Pathophysiology of endometriosis 744 Conclusions 747 Acknowledgements 748 References 748 Peritoneal fluid and the intraovarian milieu are a specific microenvironment. Peritoneal fluid originates mainly as an ovarian exudation product caused by increased vascular permeability, with cyclic variation in volume and steroid hormones which are always higher than in plasma. It contains large amounts of macrophages and their secretion products, and has a large exchange area with plasma through the peritoneum, which is highly permeable for small molecules. Diffusion becomes virtually zero for molecules with a molecular weight of >100 000 Da. In women with the luteinized unruptured follicle (LUF) syndrome, concentrations of oestrogens and progesterone are much lower in the luteal phase. Endometriosis is associated with sterile low-grade inflammation, increased concentrations of activated macrophages and many of their secretions, such as cytokines, growth factors and angiogenic factors. Concentrations of CA-125 and of glycodelins are also increased, secreted locally by the endometrial cells. Natural killer (NK) cell function declines, possibly mediated by glycodelins or local intercellular adhesion molecule (ICAM)-1 shedding. The ovary is also a specific microenvironment, with steroid hormone concentrations 1000-fold higher in follicles than in plasma. Endometrial and superficially implanted cells are influenced by peritoneal fluid concentrations so that local environment, rather than inherent cellular differences could explain differences between superficial endometriosis and eutopic endometrium. Differences between superficial implants and endometriotic disease, deep infiltrating or cystic ovarian endometriosis, may thus arise via different endocrine environments. Superficial endometrial implants are regulated by peritoneal fluid factors, whereas deep endometriosis and cystic ovarian endometriosis are influenced by blood or ovarian factors. The endometriotic disease theory considers superficial endometriotic implants and their remodelling as a physiological process in most women, and concentrates on the causes of severe endometriosis such as differences in the eutopic endometrium from women with and without endometriosis (which may indicate hereditary differences), the invasiveness of some endometriotic cells in vitro, focal 'shielding' of endometriotic foci by adhesions, and inhibition of NK activity by ICAM-1 and glycodelins. Endometriotic disease is thus seen as a benign tumour. The type of cellular lesion, hereditary and immunological environments and local hormone concentrations in the ovary and in peritoneal fluid, will decide expression as cystic ovarian endometriosis, deep endometriosis or adenomyosis externa, and whether the latter is associated with adhesions.
International Journal of Molecular Sciences
Endometriosis is a common gynecological disease which is characterized by endometriotic lesions outside the uterine cavity. In this study, we investigated whether the presence of pre-existing endometriotic lesions promotes the development of new lesions due to the exchange of cells and an altered peritoneal environment. For this purpose, uterine tissue samples from FVB/N wild-type donor mice were transplanted simultaneously or time-delayed with samples from transgenic FVB-Tg(CAG-luc-GFP)L2G85Chco/J donor mice into the abdominal cavity of FVB/N wild-type recipient mice. The formation of endometriotic lesions was analyzed by means of high-resolution ultrasound, bioluminescence imaging, histology and immunohistochemistry. Moreover, immune cells and inflammatory factors in the peritoneal fluid were assessed by flow cytometry and a cytokine array. These analyses revealed that the growth of newly developing endometriotic lesions is promoted by the presence of pre-existing ones. This is no...
Peritoneal endometriosis: validation of an in-vivo model
Human Reproduction, 2001
BACKGROUND: The current medical treatment of endometriosis, a common gynaecological disease, is still associated with a high recurrence rate. To establish an appropriate in-vivo model to evaluate new therapeutic strategies we validated the nude mouse model for the intraperitoneal cultivation of human endometrial tissue. METHODS: Human endometrium of the proliferative phase was implanted into the peritoneal cavity of normal cycling and ovariectomized athymic mice and of cycling non-obese diabetic (NOD)-severe combined immunodeficiency (SCID) mice. Morphology, proliferation, differentiation, and angiogenesis in the ectopic endometrium at different time points after implantation was investigated. RESULTS: Adhesion of endometrial fragments was observed from day 2 onwards. The lesions persisted for up to 28 days revealing a well preserved glandular morphology. The glandular epithelium maintained cytokeratin expression even after 14 days of culture. With progressing culture, glands exhibited vimentin staining in combination with a decrease of surrounding stromal cells. Proliferation of glandular epithelium could be demonstrated throughout the investigated period of 28 days, whereas expression of oestrogen and progesterone receptors was maintained only in endometriotic lesions grown in cycling but not in ovariectomized mice. Neoangiogenesis occurred from day 4 onwards, independent from the intraperitoneal localization of the ectopic lesions. CONCLUSIONS: This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.
Fertility and Sterility, 2002
Objective: To determine the effect of autologous peritoneal fluid and tumor necrosis factor-␣ (TNF-␣) on proliferation of endometrial cells from women with endometriosis. Design: Endometrial cells from eutopic and ectopic endometrium were cultured in vitro with peritoneal fluids or recombinant TNF-␣ for 72 hours before DNa synthesis determination by 3 H-thymidine labeling and liquid scintillation counting. Setting: An institute for the study and treatment of endometriosis and university-based research laboratories. Patient(s): Thirty-five women with endometriosis and 17 controls without endometriosis. Main Outcome Measure(s): In vitro incorporation of 3 H-thymidine in endometrial cells was examined. Result(s): Peritoneal fluid from women with endometriosis enhanced proliferation of autologous and heterologous endometrial cell cultures from women with endometriosis. The soluble TNF-receptor etanercept blocked the ability of peritoneal fluid from women with endometriosis to enhance proliferation of eutopic or ectopic endometrial cells. Recombinant TNF-␣ also enhanced proliferation of eutopic and ectopic endometrial cells from women with endometriosis. In contrast, autologous peritoneal fluid, heterologous peritoneal fluid from women with endometriosis, and recombinant TNF-␣ failed to enhance, and often inhibited, the proliferation of eutopic endometrial cells from controls without endometriosis. Conclusion(s): Endometrial cells from women with endometriosis can utilize factors in peritoneal fluids, such as TNF-␣, to facilitate proliferation in ectopic environments. Endometrial cells from women without endometriosis do not share this ability, suggesting that this abnormality is etiologically related to development of the disease. Therapy with agents that block the effects of TNF-␣ may be warranted.
Peritoneal Cellular Immunity and Endometriosis
American Journal of Reproductive Immunology, 1997
Peritoneal cellular immunity and endometriosis. AJRI 1997; 38:400-412 0 Munksgaard, Copenhagen PROBLEM: An immunologic basis has long been considered to be very important in the pathogenesis of endometriosis. Interactions of the peritoneal cells, which comprise macrophages, B cells, T cells, natural killer (NK) cells, and retrograde endornetrial cells, are critical, but remain controversial, for exploring the pathogenesis of endometriosis. METHOD OF STUDY Accumulated data from the literature were reviewed, and our data were analyzed. RESULTS: The data show that peritoneal macrophages are activated by the recurrent reflux of menstrual shedding. Humoral and local endometrial autoantibodies are detected in patients with endometriosis, but B cells are not quantitatively increased. There is decreased NK cell activity in the peritoneal cavity and peripheral blood, and this decreased activity may be related to the failure to clear out the ectopic endometrial tissue. Peritoneal T cells are predominant by Thl inflammatory cells, and these cells are impaired because of a decrease in activation (especially HLA-DRtCD4+CD3+ population) and in the production of interleukin-2. Inflammatory cytokines such as interleukin-I , interleukin-6, and tumor necrosis factor-a are elevated in the peritoneal fluid of women with endometriosis. CONCLUSIONS: The peritoneal NK and T lymphocytes are suppressed in women with endometriosis, but whether these immunologic deviations are the cause or the result of endometriosis is still unclear. Further studies are required to determine what role immunologic factors play in the pathophysiology of endometriosis.