Adhesion Of Endometrial Cells Research Articles

Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions

To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis, are associated with endometriosis lesions. Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction-based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. University hospital. Seventy individual patients with and without endometriosis. Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.

Cytokines and growth factors inhibit tumor necrosis factor alpha–induced up-regulation of fibronectin binding on bovine endometrial cells

To design a high-throughput cell assay to identify molecules modulating adhesion induced by tumor necrosis factor alpha (TNF-alpha) of endometrial cells to mesothelium. Prospective study. Biotech company. Bovine endometrial (BEND) and human mesothelial cells. Endometrial cells were treated with TNF-alpha and different proteins. TNF-alpha increased binding of fibronectin-coated fluorescein isothiocyanate (FITC) beads. The ability of various proteins to inhibit TNF-alpha-induced fibronectin-bead binding was measured. Treatment of BEND cells with TNF-alpha increased binding of fibronectin-coated beads. Addition of TNF-alpha-binding protein abrogated the effect of TNF-alpha in a dose-dependent manner. The initial screen of 1014 proteins identified interferon-alpha2 (IFN-alpha2), inteleukin-17 (IL-17), transforming growth factor beta (TGF-beta), and platelet-derived growth factor (PDGF) as inhibiting TNF-alpha-induced bead binding. Interferon-alpha2, IL-17, and TGF-beta inhibited bead-binding with an IC50 (ng/mL, mean +/- SD) of 0.15 +/- 0.11, 0.098 +/- 0.008, and 5.91 +/- 0.72, respectively. All three isoforms of PDGF (AA, AB, and BB) were also found to inhibit TNF-alpha-induced bead-binding, with IC50s (ng/mL) of 1.8 +/- 0.45, 10.0 +/- 1.49, and 1.72 +/- 0.73, respectively. We describe a novel high-throughput cell-based assay for endometrial cell binding to fibronectin. We show that IFN-alpha, IL-17, TGF-beta, and PDGF have inhibitory actions on adhesion of endometrial cells to fibronectin.

High soluble CD44 concentration in peritoneal fluid in endometriosis

The concentration of the soluble form of CD44, a competitive inhibitor for CD44 and hyaluronic acid binding, is higher in the peritoneal fluid of patients with endometriosis than in the peritoneal fluid of patients without endometriosis.

Effects of galectin-3 inhibition on endometrial cell cycle and adhesion

Galectin-3 (gal-3) and its ligands have been implicated in cell transformation and cancer metastasis. Gal-3 protein has been found in uterine epithelial cells adjacent to implanting blastocysts in different cell types. In order to investigate the role of gal-3 in the establishment of human endometrial receptivity, the expression of gal-3 in human endometrial cell line RL95-2 was silenced by RNA interference technology using gal-3 specific small RNA. The expression of gal-3 was detected by the reverse transcriptase-polymerase chain reaction and Western blot analysis. After the suppression of gal-3, cell cycle changes and the expression of integrin β1 were detected by flow cytometry. The adhesive ability of RL95-2 cells was analyzed by the adhesion test. Gal-3 siRNA transfection efficiency reached 70%-90%. The expression of gal-3 mRNA and protein in RL95-2 cells was strongly inhibited by 70%-90% after RNA interference. Inhibition of gal-3 expression decreased S-phase but increased G1 phase cells. Integrin β1 expression was down-regulated, and the adhesive ability of RL95-2 cells to fibronectin (FN) was significantly reduced. Gal-3 may be involved in the establishment of endometrial receptivity by regulating the proliferation and adhesion of endometrial cells. The influence on adhesion may be related with the integrin modulation.

Increased activation of nuclear factor-kappa B (NF-κB) in isolated peritoneal macrophages of patients with endometriosis

Endometriosis is characterized by pelvic inflammation that shows an increased number of activated peritoneal macrophages and their secreted products such as cytokines, growth factors, and angiogenic factors. Our results show that activation of nuclear factor-kappa B (NF-kappaB), a pro-inflammatory transcription factor, is statistically significantly increased in peritoneal macrophages from patients with endometriosis when compared with controls.

In Vivo Regulation of p38 MAPK Activation in Human Endometrium and Endometriosis

The p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to stress and therefore called as the “stress-activated kinase” which promotes inflammation. The human endometrium is a dynamic tissue that undergoes cyclical changes which include proliferation and differentiation in response to autocrine and paracrine stimuli. Endometriosis is an estrogen dependent inflammatory disease that involves endometrial cell adhesion, growth and invasion in ectopic sites such as the peritoneum.

Matrix remodeling and endometriosis.

The physiological changes in endometriosis involving multiple steps of matrix remodeling include abnormal tissue growth, invasion, and adhesion formation. Endometriosis-associated abnormal matrix remodeling is affected by several molecular factors including proteolytic enzymes and their inhibitors, which mediate tissue turnover throughout the reproductive tract to maintain the integrity of the endometrium, and ovarian steroids, which normally regulate reconstruction and breakdown of endometrium in the menstrual cycle. In addition, various growth factors, such as platelet-derived growth factor, transform growth factor β, and epidermal growth factor, direct modulation of growth, activation, and chemotaxis which may facilitate endometrial cell adhesion onto the peritoneal mesothelium during the development of endometriosis. Furthermore, cell adhesion molecules are believed to be critically involved in most cellular-level processes including cellular differentiation, motility, and attachment with the extracellular matrix. The present review focuses on the abnormal matrix remodeling process and its possible regulatory mechanism in association with endometriosis development. As a greater understanding of the cause of endometriosis is achieved, better treatment of the disease and its prevention become possible. (Reprod Med Biol 2005; 4: 93-99).

Oxidative stress and endometriosis

Little is known about the aetiology of endometriosis; however, in the presence of oxidative stress, reactive oxygen species might increase growth and adhesion of endometrial cells in the peritoneal cavity, leading to endometriosis and infertility. Within a study investigating persistent organic compounds and endometriosis, the authors evaluated the association between oxidative stress and endometriosis. Women aged 18-40 years who were undergoing laparoscopy were contacted to participate in the study (n = 100); 84 were eligible and agreed to be interviewed; 78 provided blood specimens. Four markers of oxidative stress and antioxidant status were measured in serum for 61 women. Multiple imputation of missing data was used to generate values for the missing oxidative stress data. Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not, including 22 undergoing tubal ligation and 30 with idiopathic infertility. There was a weak association between thiobarbituric acid-reactive substances (nmol/ml) and endometriosis, after adjusting for age, body mass index, current smoking, hormone use in the past 12 months, gravidity, serum vitamin E, serum estradiol, and total serum lipids (beta = 1.18; 95% CI-0.04, 2.39). These results suggest that oxidative stress might play a role in the development and progression of endometriosis, which should be evaluated in larger studies.

OXIDATIVE STRESS AND ENDOMETRIOSIS

ISEE-482 Introduction: Little is known about the etiology of endometriosis; however reactive oxygen species may increase growth and adhesion of endometrial cells in the peritoneal cavity leading to endometriosis and infertility. Within a study investigating persistent organic compounds and endometriosis, the authors evaluated the association between oxidative stress and endometriosis. Methods: Women aged 18-40 who were undergoing laparoscopy were contacted to participate in the study (n=100); 84 agreed to be interviewed and 78 provided blood specimens. Thirty-one women had visually confirmed endometriosis at laparoscopy and 53 did not, of whom 25 had surgery for sterilization and 28 for reasons related to difficulty becoming or staying pregnant. Markers of oxidative stress and antioxidant status were measured in serum for 61 women. Multiple imputation of missing data was performed using the expectation maximization [EM] algorithm. Twenty datasets were imputed and combined using logistic regression taking into consideration the with-in and between data set variance. Sensitivity analysis for power and selection bias was done. Results: There was no association detected between endometriosis and markers of oxidative stress processes as measured by thiobarbituric acid reactive substances (TBARS) (beta=−0.097; p=0.79), 8-isoprostane (beta=−0.001; p=0.30), and paraxonase activity (beta=−0.002; p=0.45). Antioxidant status as measured by beta-carotene (beta=3.211; p=0.33), vitamin A (beta=0.041; p=0.55), vitamin E (beta=0.088; p=0.24), and lycopene (beta=−2.762; p=0.29) was not significantly associated with endometriosis. Current smoking (odds ratio [OR] 5.59; 95% confidence interval [CI] 1.71-18.20) and BMI (OR 0.88; 95% CI 0.79-0.98) were significant predictors of endometriosis. Discussion: Based upon oxidative stress markers measured in serum, there does not appear to be an association between oxidative stress and endometriosis. A discussion of the results in relation to the methodology and current literature is provided.

Inhibition of the O-glycan elongation limits MUC1 incorporation to cell membrane of human endometrial carcinoma cells

We have studied how benzyl-N-acetyl-alpha-D-galactosaminide, O-glycosylation inhibitor, affects the polymorphism and shedding of membrane-bound MUC1 mucin, and change in adhesive properties of cancer cells. In endometrial adenocarcinoma cells (Ishikawa line), high molecular weight MUC1 mucin was shed from cellular membrane and could be detected in culture medium 24 h after [14C]threonine labelling. Short-time (2 days) exposure of these cells to benzyl-N-acetyl-alpha-D-galactosaminide was associated with a reduction in sialic acid level and increase in T antigen content in cellular MUC1 mucin. These changes could be inverted after removal of the inhibitor. A longer, 6-day action of the inhibitor induced a decrease in sialic acid and T antigen levels in cellular MUC1 mucin. Benzyl-N-acetyl-alpha-D-galactosaminide treatment caused the occurrence of a few incompletely glycosylated glycoforms of MUC1 in cells, but not in culture medium. Adhesion of endometrial cells to ECM compounds (type I collagen) was increased by benzyl-N-acetyl-alpha-D-galactosaminide treatment, indicating that glycosylation of extracellular domain of MUC1 can modulate adhesive properties of cells.

Adhesion of endometrial cells labeled with 111Indium-tropolonate to peritoneum: a novel in vitro model to study endometriosis

Objective To evaluate, in a new original in vitro assay, putative factors that could modulate the adhesion of endometrial cells to peritoneum. Design Prospective, controlled in vitro study. Setting Academic research laboratory. Patient(s) Fourteen nonmenopausal women undergoing hysterectomy or laparoscopy for benign gynecologic indication. Intervention(s) Endometrial cells obtained from women with regular cycles without endometriosis were labeled with 111Indium and confronted in vitro with mouse peritoneum in the presence of various cytokines and/or antiadhesive compounds. Main outcome measure(s) Radioactivity in 111Indium-labeled endometrial cells. Result(s) The adhesion of human endometrial cells to mouse peritoneum was increased by treatment with pro-inflammatory cytokines (interleukin IL-1β, IL-6, TNF α, TGF-β1). Whereas heparan sulfate had no effect on cell adhesion, a gel of ferric hyaluronate (Intergel) was able to counteract the pro-adhesive effect of cytokines. Interestingly, the pretreatment of peritoneum with cytokines, 24 hours before cell seeding in the presence of the ferric hyaluronate gel, restored the cytokine-promoting effect on cell adhesion. Conclusion(s) Proinflammatory cytokines promote the in vitro peritoneal adhesion of endometrial cells. An antiadhesive hyaluronate gel used in clinics decreases the adhesion in a dose-dependent manner and reduces cytokine bioavailability.

Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice

Objective: To investigate the role of different cellular types (epithelial and stromal endometrial cells and peritoneal cells) in the ectopic implantation of endometrium and to evaluate the importance of endocrine environment on the adhesion of endometrial cells to the peritoneum. Design: Experimental prospective study. Setting: University hospital, department of cell biology. Animal(s): One hundred one nude mice. Intervention(s): Monolayer culture of human epithelial and stromal endometrial cells obtained from patients undergoing hysterectomy or laparoscopy for benign disease. Intraperitoneal injection of cells into nude mice. Main Outcome Measure(s): Two weeks after cell injection, adhesion of endometrial cells was evaluated by histological and immunohistochemical examination. Result(s): Mixed cultures of stromal and epithelial cells, but not purified epithelial or stromal cells alone, adhered to the mouse peritoneum and led to endometriotic-like nodules. Pretreatment of cells with estrogen alone or with estrogen and progestin resulted in a higher percentage of animals developing endometriotic-like nodules, whereas treatment with progestin alone did not affect endometriotic implantation. Conclusion(s): Our data indicate that the success of endometrial cell implantation is dependent on the cooperativeness between stromal and epithelial endometrial cells, as well as on the endocrine environment of endometrial cells, but not that of recipient animals. The results emphasize the role of both endometrial cell types for ectopic implantation.

Local cytokines in endometrial tissue: the role of interleukin-8 in the pathogenesis of endometriosis.

Endometriosis, defined by the presence of viable endometrial tissue outside the uterine cavity, is among the most common gynecologic disorders affecting women of reproductive age. Endometriosis is associated with an inflammatory peritoneal environment, where multiple cytokines and growth factors are found at elevated levels. Interleukin-8 (IL-8) is a cytokine that induces chemotaxis of neutrophils and is a potent angiogenic agent. In addition, IL-8 was recently found to stimulate proliferation of various cells. We have observed that IL-8 is elevated in the peritoneal fluid of women with endometriosis and the levels correlate with the severity of the disease. We hypothesized that IL-8 may play a role in the growth and maintenance of ectopic endometrial tissue not only by chemoattracting and stimulating leukocytes to secrete growth factors and cytokines, but also by directly affecting endometrial cell proliferation. We found that IL-8 mRNA and protein levels in the endometrium were significantly higher during early proliferative and late secretory phases than during the mid-cycle. IL-8 receptors A and B are also expressed in the endometrium mostly localized in the stroma. Interestingly, IL-8 receptor expression is higher in the eutopic endometrium of women with endometriosis compared to the endometrium of women without endometriosis. Endometrial cells in culture proliferate significantly when treated with IL-8, which is inhibited by anti-IL-8 neutralizing antibody. More convincingly, IL-8 antisense oligonucleotide treatment decreases IL-8 production by endometrial cells as well as cell proliferation when compared to non-sense oligonucleotide treatment. The addition of IL-8 reverses the inhibitory effect of IL-8 antisense oligonucleotides on cell proliferation. These findings suggest that IL-8 may act as an autocrine growth factor in the endometrium. We have also studied the effect of endometrial cell adhesion on IL-8 expression and observed that IL-8 stimulates the adhesion of endometrial cells to fibronectin. Treatment of the cells with anti-IL-8 neutralizing antibody inhibited partially the cell adhesion. Thus, IL-8 may also be relevant for stimulating the attachment of endometrial implants in the pathogenesis of endometriosis. In addition, adherence of endometrial cells induced further IL-8 expression by an integrin-dependent mechanism. In summary, IL-8 may act as an autocrine growth factor in the endometrium and may also play a role in the pathogenesis of endometriosis by promoting the vicious circle of endometrial cell attachment, cell growth, and further secretion of this cytokine.

Implantation of human menstrual endometrium into nude mice

Objective: In the present study, human menstrual endometrium was transplanted into 66 nude mice in order to 1) examine the early stages of evolution of the endometriotic lesion, 2) to test whether the cellular, seric and red blood cell fractions from the menstrual effluent may have an influence on the development of endometriotic lesions in this animal model and 3) to investigate whether adhesion occurs on intact peritoneum or at the site of incision. Design: In a first series of experiments (n = 10), the timing of adhesion of menstrual endometrial tissue was analyzed by removal of the transplant on days 1, 3 and 5. In a second series (n = 25), 5 different fractions of menstrual effluent were transplanted by minilaparotomy performed on the ventral midline: 1) effluent as a whole, 2) seric fraction, 3) cellular + seric fractions 4) cellular + red blood cell fractions and 5) cellular fraction only. In a third series (n = 31), the same fractions, except the seric, were deposited by an incision on the ventral right side in order to test if the site of adhesion is influenced by the healing area. Materials/Methods: Menstrual effluent was obtained from women on day 2 or 3 of the cycle, by aspiration. The effluent was centrifuged and the seric fraction collected. Endometrial tissue was separated from red blood cells following two centifugations on Ficoll-Paque gradients and both fractions were resuspended in serum-free medium. Endometrial cell viability was checked by trypan blue exclusion. Minilaparotomy was performed in order to inject the various fractions into the peritoneal cavity of nude mice. Removal of the transplants was performed by laparotomy. Adhesion of endometrial cells and the early stages of development of endometrial lesions were studied morphologically and immunohistochemically. Staining of iron deposits and Ki67, a marker of cell proliferative activity, was carried out. The χ2 test was used for statistical analysis. Results: As early as day 1, stromal cells were found to adhere to the peritoneal mesothelium. A progressive reorganization of epithelial and stromal cells was observed. On day 5, typical endometriotic lesions, still with some necrotic areas but also large areas of normal-looking stroma and cystic glands with flattened or columnar epithelium, were present in 75% of cases. An increased rate was found when either total menstrual effluent or the cellular fraction associated with the red blood cell fraction was injected (82% and 89% respectively), when compared with rates observed after injection of the cellular fraction alone (50%) or associated with the soluble fraction (75%). A significant increase (p < 0.02) in glandular proliferative activity was observed on day 5 compared to values observed on days 1 and 3. The proliferative activity was similar whatever the injected fraction. Iron deposits were observed independently of the fraction injected. There was a tendency towards increased hemosiderin deposits when red blood cells were injected together with the cellular fraction. Implantation occurred on incision sites as well as intact mesothelium whether laparotomy was performed medially or on the right side. Conclusions: Implantation of endometrial cells can occur on intact mesothelium but may be favored by the presence of red blood cells as well as the occurrence of a peritoneal injury. Supported By: Grant 7.4530.98 from the “Fonds National de la PRecherche Scientifique de Belgique.”

Mesothelial cell–associated hyaluronic acid promotes adhesion of endometrial cells to mesothelium

Objective: To evaluate the role of hyaluronic acid in the attachment of endometrial cells to mesothelium. Design: In vitro study of adhesion of endometrial stromal and epithelial cells to mesothelial cells. Setting: University medical center. Patient(s): Reproductive-age women without endometriosis undergoing surgery for benign conditions. Intervention(s): None. Main outcome measure(s): The effect of hyaluronidase treatment of mesothelial cells or endometrial cells on adhesion of 51Cr labeled endometrial stromal and epithelial cells to monolayers of mesothelium was evaluated. The expression of CD44, the hyaluronate receptor, was evaluated by western blot. Result(s): Hyaluronidase pretreatment of mesothelial cells decreased the binding of endometrial stromal and epithelial cells to mesothelium by 39% ( P<.02) and 31% ( P<.03), respectively. There was no effect on endometrial cell binding to mesothelial cells or to collagen IV when the endometrial cells were pretreated with hyaluronidase. CD44 expression by endometrial stromal and epithelial cells was demonstrated by western blot. Conclusions: This study demonstrates that mesothelial cell–associated hyaluronic acid is involved in attachment of endometrial stromal and endometrial epithelial cells to the mesothelium. We hypothesize that binding of hyaluronic acid by endometrial cells is involved in the pathogenesis of the early endometriotic lesion.

Integrin-mediated adhesion of uterine endometrial cells from endometriosis patients to extracellular matrix proteins is enhanced by tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1)

Objectives: (1) to demonstrate specificity of integrin function in endometrial cell adhesion; (2) to investigate their regulation by tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1); and (3) to detect differences between cells from patients with and without endometriosis. Study Design: Endometrial cell cultures from ten patients with and 13 without endometriosis were tested for their expression of integrins α2β1, α5β1, ανβ3, and α4β1 by immunocytochemistry and for their adhesion to collagen type IV, laminin, and fibronectin. Results: Integrin expression was independent of cytokine treatment. Addition of antiintegrin antibodies inhibited adhesion. A significant increase in adhesion to laminin and fibronectin was seen in endometriosis after IL-1 treatment and additionally to collagen after TNFα. Cells from women without endometriosis showed a significant increase only to fibronectin. Conclusions: Human endometrial cells express functional integrins in vitro. TNFα and IL-1 had more pronounced effects on adhesion in endometriosis. Inflammatory cytokines in the peritoneal cavity may facilitate adhesion of retrogradely menstruated endometrial fragments in endometriosis.

Adhesion of human endometrial fragments to peritoneum in vitro

Objective: To evaluate the adhesion of endometrial fragments obtained during the proliferative phase of the menstrual cycle to fresh human peritoneum obtained during abdominal surgery. Design: A prospective, descriptive, morphologic and cell biologic study. Setting: Tertiary care university medical center. Patient(s): Six female volunteers. Intervention(s): After endometrial biopsies performed during diagnostic laparoscopy, endometrial fragments were generated by enzymatic digestion and mechanical separation. Peritoneum was obtained during abdominal operations for benign indications. Main Outcome Measure(s): Adhesion of endometrial fragments was studied by histologic examination and scanning and transmission electron microscopy. Result(s): After incubation, the mesothelium was intact in some areas, whereas in other areas mesothelial cells were damaged or absent. Adhesion of endometrial fragments was observed only at locations where the basement membrane was exposed. In areas largely denuded of mesothelial cells, endometrial fragments spread over the basement membrane to form monolayers. Conclusion(s): Human peritoneum is suitable for studying the adhesion of endometrial fragments. Intact mesothelium prevents the adhesion of endometrial fragments, suggesting that trauma to the mesothelial lining is a prerequisite for endometrial cell adhesion.

Tenascin is differentially expressed in endometrium and endometriosis.

Endometriosis is characterized by the presence of functional endometrial tissue outside the uterine cavity, most commonly on the ovary and peritoneum. The aetiology of endometriosis is not understood, although the adhesion of endometrial cells to the extracellular matrix (ECM) would be expected to play a central role in its pathogenesis. The expression of ECM molecules in endometrium and in endometriosis has been investigated using immunohistochemistry and western blotting techniques. The ECM components collagen IV, laminin, vitronectin, and fibronectin had a similar pattern of expression throughout the menstrual cycle in endometrium and endometriosis. Expression of tenascin was elevated in the stroma of the functionalis region of the endometrium during the proliferative stage of the menstrual cycle and in endometriosis. Tenascin expression in endometriosis was not modulated according to the stage of the menstrual cycle. It is concluded that expression of tenascin is strictly regulated in endometrium and may be important in endometrial regeneration and in the pathogenesis of endometriosis.

An experimental model for the endometriosis in athymic mice.

Endometriosis is an adhesion disorder characterized by the presence of endometrial tissue in ectopic sites outside the uterus. The disease is associated with dysmenorrhea, pelvic pain and infertility. Although endometriosis is the most common gynecologic disorder, relatively little is known regarding its etiology, pathogenesis and the course of the disease. This situation is primarily due to the absence of experimental systems to examine the mechanism of endometrial cell adhesion, role of inflammatory cells and the interactions of epithelial, and stromal cells with the peritoneum and ovarian tissue leading to the development of this disorder. Dissociated human endometrial cells were suspended in peritoneal fluids of individuals with and without endometriosis and were injected into the peritoneal cavity of athymic mice. This led to development of ectopic adhesions of endometrial cells at the peritoneal and ovarian surfaces. Endometrial cells which were marked with fluorescent lipophylic dyes, prior to intraperitoneal injection, could be visualized without surgery at such sites. The studies demonstrate a model for endometriosis in athymic mice.

Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study.

One of the first steps in the pathogenesis of endometriosis is the attachment of the endometrium to the peritoneal lining. Since the peritoneum is extremely fragile and hard to obtain, amnion has been used as an in-vitro model to study adhesion. Scanning and transmission electron microscopy was applied to evaluate the adhesion of endometrial cells isolated in the proliferative and secretory phases of the menstrual cycle. Endometrial fragments obtained in either phase of the cycle were able to adhere to the extracellular matrix of the amnion. Fragments from proliferative phase endometrium showed active spreading and growth over the matrix surface, whereas fragments from secretory phase endometrium did not. Fragments from proliferative as well as secretory phase endometrium were able to adhere to the epithelial side of the amnion, but only at locations where the amniotic epithelium was damaged or partly absent. These observations indicate that the basement membrane and extracellular matrix provide a suitable substrate for endometrial cell attachment and growth and that endometrial cell adhesion occurs preferentially to subepithelial structures, whereas an intact epithelium prevents the adhesion of endometrial fragments to the amnion.