Eutopic Endometrium In Endometriosis Research Articles

Identification biomarkers of eutopic endometrium in endometriosis using artificial neural networks and protein fingerprinting

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip array technology was used to detect biomarkers of eutopic endometrium in endometriosis patients. Five potential biomarkers (6,898 m/z, 5,891 m/z, 5,385 m/z, 6,448 m/z, and 5,425 m/z) were found.

Expression of nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) on the eutopic endometrium of the patients with endometriosis

OBJECTIVE: Altered regulation of apoptosis in eutopic endometrium could contribute to survival of endometriotic cell and developed endometriosis. NAG-1, member of transforming growth factor – β (TGF- β) superfamilies, concerns in induction of cell apoptosis. We hypothesized that decreased expression of NAG-1 of eutopic endometrium may be involved in the pathophysiology of endometriosis and investigated the expression of NAG-1 in eutopic endometrium of endometriosis and normal endometrium.

Expression of integrin beta3 and osteopontin in endometrium of patients with adenomyosis

To investigate the expression of integrin beta3 and osteopontin (OPN) in eutopic and ectopic endometrium of adenomyosis. From January 2007 to July 2008, the endometrium specimens were collected from 43 patients with adenomyosis undergoing hysterectomy in Peking University First Hospital. Eutopic endometrium were 11 in proliferative phase and 32 in secretory phase (18 cases in mid-secretory phase) were collected. Ectopic endometriums were also collected. In the mean time, it was chosen 41 cases with pure subserous uterine myoma or cervical intraepithelial neoplasia (CIN) II-III treated by hysterectomy as controls including 12 endometrium in proliferative phase and 29 endometrium in secretory phase (19 cases in mid-secretory phase). The expression of Integrin beta3 subunit and OPN in the endometrium were assessed by immunohistochemical staining and quantitative real-time polymerase chain reaction. (1) Immunohistochemical staining showed that positive staining of integrin beta3 and OPN were present predominantly in eutopic and ectopic endometrial glandular epithelium. There was significant different protein expression of integrin beta3 and OPN, which were 1.6 +/- 0.8 and 1.7 +/- 0.7 in eutopic endometrium, 1.7 +/- 0.7 and 1.8 +/- 0.9 in ectopic endometrium, 2.1 +/- 0.9 and 2.0 +/- 0.9 in control endometrium (P < 0.05). The protein expression of integrin beta3 and OPN in eutopic endometrium of adenomyosis in the proliferative phase (0.8 +/- 0.4 and 0.7 +/- 0.3) were remarkably lower than those of the secretory phase (1.8 +/- 0.8 and 1.9 +/- 0.8, P < 0.01). The protein expression of integrin beta3 and OPN in the endometrium of controls in the proliferative phase (1.0 +/- 0.4 and 1.0 +/- 0.4) were significantly lower than those of the secretory phase (2.5 +/- 0.7 and 2.5 +/- 0.7) (P = 0.000). In the mid-secretory phase, the protein expression of integrin beta3 (2.0 +/- 0.9) and OPN (2.1 +/- 0.8) in eutopic endometrium of adenomyosis were significantly lower than that of control endometrium (2.7 +/- 0.5 and 2.7 +/- 0.7) (P < 0.01). (2) The mRNA expression level of integrin beta and OPN in eutopic and ectopic endometrium were assessed by quantitative real-time PCR (result was shown by median index). It was observed that integrin beta3 mRNA and OPN mRNA were significantly lower in the eutopic endometrium of adenomyosis (4.69 and 4.23), when compared with ectopic endometrium (7.96 and 14.84) and controls (13.47 and 17.40) (P < 0.05). Eutopic endometrium had higher mRNA expression of integrin beta and OPN mRNA in the secretory phase (5.54 and 11.40) than that in the proliferative phase (2.69 and 3.30) (P < 0.01). The mRNA expression level of integrin beta and OPN of control endometrium in the proliferative phase (3.12 and 4.75) were significantly lower than that in the secretory phase (19.94 and 21.00, P = 0.000). The mRNA expression of integrin beta and OPN were 10.10 and 14.34 in the mid-secretory phase, which were significantly lower than 21.50 and 24.18 in control endometrium (P < 0.05). High expression of integrin beta3 and OPN in ectopic endometrium of adenomyosis may cause endometriotic lesions; abnormal expression of integrin beta3 and OPN in the endometrium of adenomyosis during the implantation window may contribute to infertility in some patients.

Prokineticin 1 mRNA expression in the endometrium of healthy women and in the eutopic endometrium of women with endometriosis

To examine prokineticin 1 (PROK1) mRNA expression in eutopic endometrial glands obtained from patients with or without endometriosis, to investigate the presence of additional endometrial abnormalities in women with endometriosis. Prospective laboratory study. University hospital. Twelve control women and 12 patients affected by endometriosis in the secretory phase of the menstrual cycle. Endometrial specimens were obtained from women affected (cases) or not (control group) by endometriosis. Endometrial glands were freshly isolated from endometrial biopsies. PROK1 mRNA expression levels by real-time polymerase chain reaction analysis. PROK1 mRNA was detectable in 4 of 12 (33%) samples obtained from women affected by endometriosis, whereas 10 of 12 (83%) samples obtained from normal women were positive for PROK1 detection by real-time polymerase chain reaction. Moreover, detectable PROK1 mRNA levels were 10 times lower in samples obtained from women with endometriosis than in samples obtained from control women. PROK1 is a newly discovered angiogenic factor implicated in the vascular function of peri-implantation endometrium and early pregnancy. An altered expression of PROK1 could be one of the several biochemical abnormalities characterizing eutopic endometrium in endometriosis.

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

In order to investigate the role of the nuclear factor kappaB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkappaB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

Expression of Annexin-1 in patients with endometriosis

Annexin-1 was identified as an endometriosis-related protein by comparative proteomics in previous study. As an endogenous anti-inflammatory mediator, Annexin-1 has been shown to regulate the immune response, cell proliferation and apoptosis. To investigate whether Annexin-1 is involved in the pathogenesis of endometriosis, we examined the expression of Annexin-1 in eutopic endometrium of women with or without endometriosis, and detected its expression in peritoneal fluids of those with endometriosis. Eutopic endometrium samples from twenty-five women with endometriosis and those from sixteen age-matched women without endometriosis were collected. Peritoneal fluids were obtained from ten patients with endometriosis. The expression of Annexin-1 protein in eutopic endometrium was detected by immunohistochemistry and Western blotting, and mRNA detected by real-time PCR. Annexin-1 protein in the peritoneal fluids was detected by Western blotting. Annexin-1 mRNA and protein were overexpressed in eutopic endometrium of endometriosis without significant differences between the proliferative and secretory phase. Immunohistochemistry showed that Annexin-1 protein was expressed mainly in endometrial glandular cells throughout the menstrual cycle. Annexin-1 protein was detected in the peritoneal fluids of all the ten patients with endometriosis. Annexin-1 is overexpressed in eutopic endometrium and presents in the peritoneal fluids of patients with endometriosis, and may play a role in the pathogenesis of endometriosis.

Decreased suppression of interleukin-6 after treatment with medroxyprogesterone acetate and danazol in endometrial stromal cells of women with adenomyosis

To examine changes in local cytokine production in the eutopic endometrium of adenomyosis after treatment with medroxyprogesterone acetate (MPA) and danazol. Prospective cohort study. Tertiary university hospital. Twenty-four women with adenomyosis (study group) and 22 women without adenomyosis (control group). Eutopic endometrium was separated into single endometrial stromal cells (ESCs), and was cultured in vitro alone, with MPA (10(-7) M), or with danazol (10(-7) M) for 8 days. Messenger RNA expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha in ESCs, and their concentrations in the supernatants of ESCs. A significant decrease of IL-6 concentration in the supernatant, measured by ELISA, was found with time of ESCs cultured with MPA and danazol in the control group, but not in adenomyosis. The IL-6 mRNA in ESCs determined by real-time quantitative polymerase chain, as well as its concentration in the supernatant, was much higher in adenomyosis than that in the control group after treatment with MPA and danazol for 8 days. Medroxyprogesterone acetate and danazol appeared to have a decreased effect on the suppression of IL-6 liberated by ESCs in adenomyosis. This aberrant secretion of IL-6 might play a role in the formation of ectopic endometrial implants in adenomyosis.

P-333: Expression of cyclinB1, cdc2 and polo-like kinase1 in ectopic and eutopic endometrium of endometriosis

P-333: Expression of cyclinB1, cdc2 and polo-like kinase1 in ectopic and eutopic endometrium of endometriosis

GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis.

Because overproduction of nitric oxide (NO) and peroxynitrite is known to cause tissue injury, the expression of NO synthases (NOS) and generation of peroxynitrite were investigated in adenomyosis. Immunoreactivities to endothelial and inducible NOS demonstrated phase-dependent changes in normal endometrium, and in eutopic endometrium of adenomyosis. However, NOS were expressed throughout the menstrual cycle in ectopic endometrium from the majority of patients with adenomyosis. Nitrotyrosine, a footprint of peroxynitrite, was detected concomitantly with NOS protein. This suggested that high doses of NO and superoxide are produced in the ectopic endometrium, presumably by stimulation with bioactive molecules such as cytokines and growth factors. The expression of NOS and generation of peroxynitrite were markedly reduced by administration of gonadotrophin-releasing hormone agonists (GnRHa). The suppression of serum concentrations of nitrite/nitrate, stable metabolites of NO, by long-term administration of GnRHa was also demonstrated. The suppression of synthesis of NO and/or peroxynitrite may be part of both the therapeutic and adverse effects of GnRHa therapy.

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.

Phenotypic and functional studies of leukocytes in human endometrium and endometriosis.

The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity. These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle. Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium. Apoptotic cells were rarely found in control and subject endometria. In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders. The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation. Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells. eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses. eGLs are evidently functionally important in the eutopic endometrium. Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.