| Endometriosis is a common gynecological disease that influences women in reproductive age. As reported before, the disease happens to 60 percent of women with dysmenorrhea, 40-50 percent of women with chronic pelvic pain and dyspareunia. And the study of epidemiology showed that the incurrence of the disease had a positive correlation to the status of society and economics. Recently as the progression of diagnosis, it seems that the incurrence has increased. Although the pathology of the disease is benign, malignant biologic activation of endometriotic cell is often seen according to the clinical symptoms, namely aggravating and persistent pelvic pain, dysmenorhea, infertility and dyspareunia which have disturbed doctors much.Lately researchers have made great progression in melocular pathogenesis of the disease. Based on that, the theory that endometriosis decided by eutopicendometrium was confirmed. Followed which there was the program of pathogenesis of the disease, namely attachment, invasion and angiogenesis. Among them, adhesion is the first stage in the framework of endometrial cell to invade the peritoneum and the surface of other organs, followed by invading the extracellular matrix and angiogenesis which are the indispensable condition for the implantation of endometrial cell. Lots of correlated factors and enzymes were proved to be involved and the effect of steroid hormone, immune system and local environment make the process quite complicated, too. Exploring the discrimination of eutopic endometrium between women with endometriosis and without becomes the important portion in the pathogenesis of the disease, which includes the difference in ultrastructure and expression of key factors. For example, P450, VEGF, Survivin, MMP and TIMP, also the macrophage's activation and the factors it secrets have been proved to related with the pathogenesis and progression of endometriosis.Macrophage migration inhibitory factor (MIF) is a product from T lymphocyte which can inhibit the migration of macrophage. And recent studies hint to us that MIF might play a role in the angiogenesis that related with endometriosis. Some researches recently also suggest us that MIF might contribute to the pathogenesis of endometriosis.To make the role that MIF might play in the pathogenesis of endometriosis clearer, our study explored the alteration of MIF expression in eutopic endometriumof women with endometriosis and the correlation between MIF expression and clinical symptoms.Materials and methodsA total of 102 women in reproductive age operated on in gynecologic department of the Second Affiliated Hospital, School of Medicine, Zhejiang University volunteered for this study. All women had normal menstrual cycles and had not received any anti-inflammatory or hormonal treatment for at least 3 months. There was no significant difference between the age of women with endometriosis and control group.Among 55 patients,35 cases with ovary endometriotic cyst who was diagnosed as endometriosis, 14 cases combined with pelvic endometriotic lesion, 6 cases combined with adenomyoma. And there were 47 cases in the control group operation for hysterectomy for uterine myoma. And all the 47 patients were confirmed no inflammation and endometriotic lesion during the operation.According to the Noyes pathological diagnosis (Hematoxylin-Eosin staining) endometrial samples were divided into four groups: proliferative phase of endometriosis (26 cases), secretory phase of endometriosis (29 cases), proliferative phase of control (24 cases), secretory phase of control (23 cases).MIF expression in endometrial samples was assessed by immunohistochemistryand western blotting analysis. All data were in normal distribution and statistical analysis of ratios of MIF/β-actin was performed using one-way ANOVA by SPSS 11.5 software. And results were expressed as means ± SD. Multiple comparisons were performed using the Bonferroni t procedure and single comparisons using Student' s t test.Result1 , The location of MIF in endometrium MIF immunoreactive staining was present in the cytoplasm of glandular epithelial and stromal cells in both women with and without endometriosis. The intensity of immunoreactive staining in gradular epithelium was higher than in stroma.2, Difference of MIF protein expression in endometrial tissues from different groups:The anti-MIF antibody detected a band at 12.5kDa in protein extracts from all endometrial tissues. After normalizing each band of MIF with β-actin from different samples, we found that the average level of MIF expression of women with endometriosis at proliferative and secretory phase (0.22±0.04, 0.23±0.04, respectively) were significantly higher than that of control (0.19±0.03, 0.21±0.03, respectively) (P<0.05).3, The level of MIF expression in endometrium of women with endometriosis in different stage: Not only at proliferative phase, also at secretory phase MIFexpression level of women with endometriosis in higher disease stages were increased compared to those in lower stages(P = 0.032<0.05, P = 0.005<0.01, respectively). There was a positive correlation between disease stage and MIF expression.4, The different level of MIF expression in endometriosis with dysmenorrhea and pelvic pain or not: Our result showed that at both proliferative and secretory phases, the level of MIF expression of endometriosis with dysmenorrhea or pelvic pain is significantly higher than those without (P<0.05).ConclusionAs a factor that can inhibit migration and promote secretion of macrophage, MIF was found in the grandular epithelium and stroma of endometrial tissues. MIF expression was increased in eutopic endometrium of women with endometriosis and had a positive correlation with stage of the disease, dysmenorrhea and pelvic pain. These results suggest us that MIF might play a role in the pathogenesis and progression of endometriosis. |
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