| BackgroundEndometriosis is a common gynecologic disease, but the exact pathophysiology of this enigmatic disease is still unknown. As is well known, although dissemination of the endometrial cells into ectopic locations during menses appears to be a common phenomenon, ectopic implantation of these cells takes place in only minority women. Some studies showed that eutopic endometrium from women with endometriosis differ from those from normal women in many cytokines.Interleukin-18 (IL-18), a novel cytokine, plays an important role in immunomodulatory and anti-tumor progress. It can enhance Fas-Fas ligand mediated cytotoxicity by inducing Fas ligand expression, and can augment the differentiation and activation of Thl cells. It has been found that IL-18 was constitutively expressed in endometrial epithelial cells and stromal cells throughout the menstrual cycle. We hypothesized that IL-18 was involved in the pathogenesis of endometriosis and the differences in eutopic endometrium between the patients and controls. In order to clarify this hypothesis, we examined the expression of IL-18 in eutopic and ectopic endometrium in endometriosis. According to Sampson's theory, retrograde menstruation, peritoneal adhesion of shed endometrial tissue, and outgrowth of these endometrial cells are essential steps. In order toelucidate mechanisms of formation and development of endometriosis in early stage, in the present study, we established an early stage model of endometriosis in ICR white mice and determined roles of vascular endothelial growth factor (VEGF) and (matrix metalloproteinase-2) MMP-2 in endometriosis.Objective1. To study the expression of IL-18 in eutopic and ectopic endometrium in endometriosis and the role on the pathogenesis of this disease;2. To establish the early stage model of endometriosis in ICR white mice and to observe the role of VEGF and MMP-2 in this disease;3. To study the difference in the eutopic endometrium between from patients with endometriosis and from controls.Methods and results1. Endometrium specimens were obtained from 22 normal uteruses, 26 with endometriosis and 21 with adenomyosis; endometriosic tissues from 28 patients. Immunohistochemistry was employed to determine the location of IL-18 protein, and semiquantitative reverse transcriptase polymerase chain reaction, using actin as internal standard, was applied to determine the levels of IL-18mRNA in those specimens. Results IL-18 protein was found in all specimens and the expression of IL-18mRNA was significantly lower in ectopic and eutopic endometrium from patients with endometriosis, compared with those from normal women and patients with adenomyosis (0.77 ± 0.39, 1.05 ± 0.40 and 1.65 ± 0.64, 1.63 ± 0.60, respectively, 2. P<0.05). In normal women, secretory endometrium had higher expression of IL-18mRNA than proliferative endometrium; whereas in endometriosic women, there was no difference.2. 20 endometrial samples were obtained from 10 healthy women and 10 women with endometriosis undergoing elective surgery, and each sample was cut into 2-3mm3-size fragments. A minilaparotomy was performed to place onefragment in the abdominal cavity of mouse, and every patient needed three mice. Transplants were observed and removed for immunohistochemistry study on days 1,2 and 3. Results: On day 1, all grafts but one were free in peritoneal cavities. In the margin of grafts, glandular and stromal cells appeared viable, but the inner cells are necrosis. On day 2 and 3, almost all grafts had attached to the peritoneum or periintestinal fatty tissues. Mesothelium cells had wrap up grafts incompletely. Endometrial glands and stromal cells, near the area of adhesion between graft and peritoneal layer, were clearly viable. Blood vessels were present at the junction between the transplant and mesothelium. Scores of VEGF and MMP-2 in viable glandular cells in grafts were higher than those in eutopic endometrium before transplantatio... |
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