Ectopic Endometrium In Endometriosis Research Articles

Deubiquitinase and unconjugated ubiquitin activate microenvironment inflammation and pain in eutopic and ectopic endometrium in endometriosis

Deubiquitinase and unconjugated ubiquitin activate microenvironment inflammation and pain in eutopic and ectopic endometrium in endometriosis

Molecular profile of eutopic and ectopic endometrium in endometriosis

Molecular profile of eutopic and ectopic endometrium in endometriosis

Expression of PROK 1 and its receptor PROKR 1 in endometriosis and its clinical significance

To investigate the role of prokineticin (PROK) 1 and prokineticin-receptor (PROKR) 1 in the pathogenesis of endometriosis and its clinical signifaicance. Methods: Quantitative real-time PCR (qPCR) and Western bloting were used to detect the expression of PROK 1 and PROKR 1 in eutopic and ectopic endometrium of endometriosis (n=22) and normal control endometrium (n=18). Endometrial stromal cells were isolated and cultured in 6 normal controls. The expression of PROK 1 mRNA was detected by qPCR after treated with estradiol (E2) or TNF-α. Results: PROK 1 and PROKR 1 mRNA were expressed in eutopic and ectopic endometrium of endometriosis and normal control endometrium, and the expression level gradually declined (P<0.05). The expression of PROKR-1 protein in eutopic and ectopic endometrium of endometriosis and normal control endometrium gradually declined (P<0.05). The expression of PROK-1 protein in normal control endometrial cells and eutopic endometrium cell was higher in secretory phase than in proliferative phase (P<0. 05). E2 did not change the expression of PROK 1, whereas TNF-α up-regulated the expression of PROK 1. Conclusion: PROK-1 and its receptors are involved in the pathogenesis and development of endometriosis. TNF-α can promote angiogenesis via up-regulating the expression of PROK 1.

Accents of molecular markers expression profiling in eutopic and ectopic endometrium in endometriosis

Accents of molecular markers expression profiling in eutopic and ectopic endometrium in endometriosis

Methylation status and protein expression of RASSF1A in endometriosis.

Ras association domain family 1A (RASSF1A) gene inactivation by promoter hypermethylation is a common event in the development of a variety of types of human cancer. Accumulated evidence has demonstrated that DNA methylation serve a critical role in the pathogenesis of endometriosis. The aim of the present study was to analyze the methylation status and protein expression of RASSF1A in endometriosis (EMS). The ectopic and corresponding eutopic endometrium tissues were collected from 45 women with EMS (EMS group) and normal endometrium tissues from 20 women without EMS (control group). The methylation status of RASSF1A was examined by methylation specific polymerase chain reaction (MSP). Immunohistochemistry was performed to measure RASSF1A protein level in endometrium tissues. In normal endometrium samples, RASSF1A protein expression was significantly higher at the secretory phase than the proliferative phase. RASSF1A protein expression in the ectopic endometrium tissues and eutopic endometrium tissues were significantly reduced than in normal endometrium (P<0.05). The frequency of aberrant methylation of RASSF1A was 55.56% in ectopic endometrium and 33.33% in paired eutopic endometrium, whereas such methylation was not detected in normal endometrium. Moreover, RASSF1A promoter hypermethylation was frequently associated with reduced expression of RASSF1A, and was common in advanced stage in ectopic endometrium of EMS. Epigenetic inactivation of RASSF1A through aberrant promoter methylation may be important in the formation and progression of EMS, and assessment of RASSF1A methylation status in eutopic endometrium may be a potentially useful biomarker to enhance the early detection of EMS.

Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis.

Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease.

Expression and significance of HOXA10 gene in the eutopic and ectopic endometrium of endometriosis

To investigate the expression and clinical significance of HOXA10 gene in the eutopic and ectopic endometrium of endometriosis. Mehtods Between Jan.2009 to Aug.2010, 30 patients with endometriosis undergoing laparoscopic surgery in Maternal and Children's Hospital of Foshan. Eutopic and ectopic endometrium were obtained. In the mean time, 30 patients with benign ovary cyst or tubal infertility undergoing laparoscopic surgery were selected as controls. Their uterine endometrium were obtained real-time fluorescent quantitation, western blot and immunohistochemistry technique were used to detect mRNA and protein expression of HOXA10 gene in the eutopic endometrium group, ectopic endometrium group and control group. The mRNA and protein expression of HOXA10 gene were 0.61 ± 0.07 and 0.47 ± 0.05 in the eutopic endometrium of endometriosis, 0.64 ± 0.06 and 0.50 ± 0.05 in ectopic endometrium of endometriosis, which were significantly lower than 1.22 ± 0.14 and 1.42 ± 0.14 in control group (P < 0.01). However, the mRNA and protein expression of HOXA 10 between eutopic and ectopic endometrium of endometriosis did not reach statistical difference (P > 0.05). The expression of HOXA10 in eutopic and ectopic endometrium of endometriosis were decreased by immunohistochemistry staining. The lower expression of HOXA10 gene in the eutopic and ectopic endometrium of endometriosis might be associated with pathogenesis and infertility of endometriosis.

Altered expression of activin, cripto, and follistatin in the endometrium of women with endometrioma

To evaluate the expression pattern of activin A, activin receptors, and activin modulators messenger RNA (mRNA) in the eutopic endometrium of patients with endometriosis at different phases of the menstrual cycle and to evaluate the mRNA expression of the same proteins in endometriomas during the menstrual cycle. Prospective study. University hospital. Women with and without endometriosis. Samples of endometrial and endometriotic tissue from women with endometrioma (n=48), and endometrial samples from women without endometriosis (controls) (n=48). Quantification of activin A, activin B, activin receptor II, nodal, cripto, inhibin α, and follistatin expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The eutopic endometrium of patients with endometriosis showed [1] higher activin A mRNA expression in the proliferative phase and a lack of late secretory phase peak, [2] a lack of endometrial cycle-related variations of cripto and inhibin α mRNA expression, and [3] an inverse expression pattern of follistatin mRNA. Endometriomas showed similar variations in the expression of activin-related protein mRNA during the menstrual cycle as eutopic endometrium. The disturbed expression of endometrial activin A, cripto (activin receptor antagonist), and follistatin (activin-binding protein) suggests a dysfunction of the activin pathway in endometriosis. Endometriomas showed similar changes of activin-related proteins during the menstrual cycle, which supports a common biology for eutopic and ectopic endometrium in endometriosis.

Expression of oct-4 and c-kit antigens in endometriosis

The objective of this study was to test the expression of the oct-4 and c-kit, both markers of stem cells, in the ectopic endometrial tissue of endometriotic lesions of women with severe endometriosis. Our findings show that ectopic epithelial cells express oct-4 and c-kit and this suggests that the ectopic endometrium in endometriosis has a stem cell origin and could explain the possible progression to ovarian cancer.

Cyclooxygenase-2 overexpression in ovarian endometriomas is associated with higher risk of recurrence

Cyclooxegenase-2 expression was evaluated by immunohistochemistry in endometrioma tissue samples taken from 109 patients, of whom 53 had recurrence by 30 months after surgery and 56 did not. Cyclooxegenase-2 overexpression, along with previous medical treatment of endometriosis and the presence of adhesion, is predictive of recurrence of ovarian endometrioma within 30 months after surgery, with a resultant sensitivity of 72.5% and a specificity of 72.4%, suggesting that there are intrinsic and identifiable biomarkers that confer recurrence risk.

Altered Extracellular Matrix in Eutopic and Ectopic Endometrium of Endometriosis

It is believed that the extracellular matrix (ECM) remodeling is relevant to the progression of endometriosis. The physiological changes in endometriosis involving in multiple steps of matrix remodeling include abnormal tissue growth, invasion, and adhesion phenomena. The changes of surrounding environment including the ECM expressions may affect the attachment and de-attachment of the cells. This study aims to investigate the expression pattern of various ECM molecules surrounding stromal and vascular tissues of eutopic and ectopic endometrium in patients with endometriosis.

Expression of IL-18 in endometriosis

Objective: To study the expression of interleukin-18 (IL-18) in eutopic and ectopic endometrium in endometriosis and the role on the pathogenesis of this disease. Methods: Endometrium specimens were obtained from 22 normal women, 26 patients with endometriosis and 21 patients with adenomyosis. Endometriosic tissues were obtained from 28 patients. Immunohistochemistry was employed to determine the location of IL-18 protein. Semiquantitative reverse transcriptase polymerase chain reaction was applied to determine the levels of IL-18mRNA in those specimens using β-actin as internal standard. Results: IL-18 protein was found in all specimens. Compared with endometrium from normal women and patients with adenomyosis, the expression of IL-18mRNA was significantly lower in ectopic and eutopic endometrium of the patients with endometriosis. In normal women, secretory endometrium had higher expression of IL-18mRNA than proliferative endometrium; whereas in endometriosic women, there was no difference between two phases. Women with endometriosis showed down-regulation of IL-18 expression in ectopic and eutopic endometrium, suggesting that the abnormal expression of IL-18 might play a pathogenic role in endometriosis.

Biologic aspects of endometriosis

Objective: Although endometriosis is a benign disease, the ectopic endometrium in endometriosis show an increased capacity to proliferate and to grow invasively. To determine the possible genetic aberrations and the changes in the expression level of certain adhesion molecules that could possibly contribute to the development of endometriosis. This was also assessed after the medical treatment with Zoladex 3.6 mg monthly for 6 months. Follow up revealed that such treatment is considered an effective therapeutic modality for endometriosis.

Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

Objective: To investigate the expression of xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Design: Immunohistochemical identification of xanthine oxidase in endometrial tissues by using polyclonal antibody. Setting: University hospital. Patient(s): Thirty-four women with endometriosis, 34 women with adenomyosis, and 44 fertile control women. Intervention(s): Biopsy samples were obtained from the endometrium throughout the menstrual cycle. Main Outcome Measure(s): Semiquantitative immunostaining (evaluation nomogram) score of endometrial cells. Result(s): The level of xanthine oxidase expression in the glandular epithelium of control varied according to menstrual phase, but no such variation in expression was seen in endometriosis. Variation in xanthine oxidase expression was observed during the menstrual cycle in patients with adenomyosis; this variation differed completely from that in controls. Xanthine oxidase expression was found in ectopic endometrial tissue in all cases. The mean evaluation nomogram levels in the glandular epithelium in adenomyosis tissue were as high as those in the early secretory phase in the eutopic endometrium. Conclusion(s): Aberrant expression of xanthine oxidase in eutopic and ectopic endometrium appears to play a pathologic role in endometriosis and adenomyosis.

Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis.

The objective of this study was to determine the distribution of cyclooxygenase-2 (COX-2) in eutopic and ectopic endometria in endometriosis and adenomyosis. The subjects were 35 patients with endometriosis diagnosed by laparoscopy, 33 patients with histologically confirmed adenomyosis and 50 female controls with normal fecundity. Expression of COX-2 was immunohistochemically investigated in tissues from eutopic endometrium and myometrium and ectopic endometrium of the wall of ovarian chocolate cysts using polyclonal antibody. Surface epithelial cells, endometrial glandular epithelial cells or stromal cells were assessed. Cells were semi-quantitatively assessed on a scale of 1 to 5 using a nomogram created from positive cell count and the degree of staining. COX-2 expression in surface and glandular epithelia of the control group varied markedly during the menstrual cycle. It was lowest in the early proliferative phase and gradually increased thereafter. It remained high throughout the secretory phase. However, in patients with endometriosis, expression of COX-2 in glandular epithelium was higher than that in the control group, though it varied throughout the menstrual cycle. On the other hand, there was no variation in expression of COX-2 in the adenomyosis group during the menstrual cycle, and it was lower than that in the endometriosis group in all phases. Pronounced COX-2 expression was observed in glandular cells from ectopic endometrial tissue of ovarian chocolate cyst walls in all cases regardless of the menstrual phase. In summary, increased COX-2 expression in eutopic and ectopic endometria was believed to be strongly correlated with pathological abnormalities in these disorders.

Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

Objective: To determine the expression of glutathione peroxidase (GPx) in the eutopic and ectopic endometria during the menstrual cycle in endometriosis and adenomyosis. Design: Immunohistochemical identification of GPx in endometrial tissues identified using the polyclonal antibody. Setting: Department of obstetrics and gynecology in a university hospital. Patient(s): One hundred fourteen women divided into three groups: 33 patients with endometriosis, 34 patients with adenomyosis, and 47 fertile control subjects. Intervention(s): Endometrium biopsied throughout the menstrual cycle. Main Outcome Measure(s): Endometrial cells: semiquantitative immunostaining (evaluation nomogram) score. Result(s): The analyses revealed phase-dependent changes of GPx expression in the surface and glandular epithelia in the eutopic endometrium during the menstrual cycle in the fertile controls, i.e., the expression was weak in the early proliferative phase, gradually increased, was most marked in the early secretory phase, and decreased thereafter. The expression of GPx in the eutopic endometrium in endometriosis lost the variation during the menstrual cycle. The expression of GPx in adenomyosis was persistently marked over the control levels throughout the menstrual cycle. Conclusion(s): The aberrant expression of GPx in the eutopic endometrium throughout the cycle suggests a pathological role in endometriosis and adenomyosis.

Distribution of heat shock proteins in eutopic and ectopic endometrium in endometriosis and adenomyosis

To evaluate the pathophysiologic role of heat shock proteins and to examine the effect of danazol on these proteins in patients with endometriosis and adenomyosis. Immunohistochemical identification of human heat shock proteins 27, 60, and 70 in endometrial glandular cells identified using monoclonal antibodies. Department of obstetrics and gynecology in a university hospital. Subjects were 119 women with documented endometriosis or adenomyosis. The subjects were divided into three groups: fertile control (n = 38), with 14 in the proliferative phase and 24 in the secretory phase; endometriosis (n = 38); and adenomyosis (n = 43), including 33 who underwent hysterectomy and 10 treated with danazol. Staining of glandular cells by semiquantitative immunostaining (evaluation nomogram) score. Significantly increased expression of heat shock protein 27 was noted in eutopic endometrium from patients with endometriosis and adenomyosis as compared with controls, regardless of the menstrual phase. The scores for heat shock protein 27 and heat shock protein 70 in the ectopic endometrium of patients with endometriosis were low compared with those in eutopic endometrium, whereas in adenomyosis, the scores were similar to those of eutopic endometrium. After treatment with danazol, the expression of heat shock proteins returned to control levels. We suggest that abnormally increased expression of heat shock proteins plays a role in the pathophysiology of endometriosis and adenomyosis.