Investigation Of The Efficacy Of PEDF Treatment On Experimental Endometriosis And Its Possible Mechanisms

BackgroundEndometriosis is a common gynecological disease associated with pe1vic pain and infertility, which affects the woman physical and moral integrity seriously. The prevalence is estimated about10-15%among the women in reproductive age. The causes of endometriosis remain unclear although its incidence rate tends to be incrteased. It is considered to be a beginning disorder, but it exhibits the features that malignancy really holds, for instance it is aggressive, invasive and angiogenesis. The efficacy of the current treatment including medical and surgical therapy is still not good though many treatments were carried out, the side effect is big, and medicine expense is high. So it is requisite to search for new treatment for endometriosis.Recent studies have found that vascular endothelial growth factor (VEGF) plays an important role in the development and progression of endometriosis. Application of anti-angiogenic factors promise to offer a new option for treatment of endometriosis. It can suppress the growth of endometriotic lesions and cure the disease via anti-angiogenesis. Some anti-angiogenic factors (such as endostatin, selective cyclooxygenase-2inhibitor) have been approved to be effective in suppressing the growth of endometriosis. PEDF owned a low expression in several tumors, for example breast cancer, ovarian cancer and lung carcinomas. The application or over-expression PEDF can suppress the growth of cervical carcinoma, ovarian cancer, osteosarcoma, retinoblastoma and melanoma. Recent studies also have found that it showed a low expression of PEDF in peritoneal fluid and serum, which is related to the severity and type of endometriosis, suggesting that PEDF may play an important role in the pathogenesis of endometriosis.We designed this experiment based on our hypothesis to study the effect-of CSO-SA/PEDF to endometriotic lesions in rats via intravenous injection and discuss the pathogenesis and toxicity, which may provide a safe and effective treatments for endometriosis.ObjectiveTo investgate the inhibitory effect of pigment epithelium derived-factor (PEDF) on experimental endometriosis and its possible mechanisms research. Materials and methodsFemale nonpregnant, Spraguee Dawley rats were used to establish endometriosis model by transplanting autologous fragments of uterus to the inner surface of the abdominal wall, which were treated with PEDF via IV injection. After2weeks, the endometriotic cyst was measured and observed under light microscopy. At the same time we study the pro-apoptotic and anti-angiogenic effect of PEDF to endometriosis by analyzing apoptosis, VEGF expression and microvessel density. Simultaneously we observed the side effect by histopathologic observation of the rat reproductive organ and calculate the reproductive organ exponent.Statistical analysis All data were managed with SPSS16.0for windows. Student’s t-test analysis was used for statistical analysis. P<0.05was considered to be statistically significant in all cases.Results1. PEDF gene therapy caused decrease in the sizes of the endometriotic lesions significantly (P<0.05)and atrophy and degeneration of ectopic endometrium.2. There is a reduction in microvessel density labeled by Von Willebrand factor was observed (P<0.05) and no decrease in-Smooth Muscle Ac tine-positive mature vessels.3. The expression of VEGF in stroma of endometriotic lesions in PEDf group is lower than that in control group (P<0.05)4. the index of apoptotic was increased significantly in endometriotic lesions in PEDF group (P<0.05)5. There is no significant difference between the two groups in histopathologic and ultra-structure observation of uterus and ovaries.Conclusion1. PEDF can suppress the growth of endometriotic lesions via anti-angiogenesis or/and pro-apoptosis in a rat model of endometriosis.2. PEDF has no effect on the histopathologic and ultra-structure of uterus and ovary in rats.