Pigment Epithelium Derived Factor Inhibits the Growth of Human Endometrial Implants in Nude Mice and of Ovarian Endometriotic Stromal Cells In Vitro

Abstract

Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF) is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF) expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial‐mesenchymal transition of a endometrial epithelial cells

“…Isolation of primary human endometrial epithelial cells was undertaken as described in our previous paper 37 . Then, cells were cultured in Dulbecco's Modified Eagle's medium: Nutrient Mixture F‐12 (DMEM/F 12; Keyi Biotechnology) containing penicillin (50 U/mL), streptomycin (50 μg/mL) and foetal bovine serum (FBS; 12% (v/v)), all of which were from Sigma‐Aldrich.…”

“…Isolation of primary human endometrial epithelial cells was undertaken as described in our previous paper. 37 Then, cells were cul-…”

Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain

“…The mice were tested for drug distribution 10 days after surgery. 23,31 The rats were anesthetized before making a vertical incision on the abdomen. The distal 1 cm segment of the uterine horn was extracted and immediately placed in sterile saline.…”

Role of pigment epithelium-derived factor in the reproductive system

“…We (Chuderland et al 2013c) and others (Chen et al 2011 have recently suggested the use of PEDF for treating endometriosis. Sun et al (2012) showed that PEDF gene treatment inhibits the growth of human endometriotic cells in vivo when transplanted to a nude mouse model; they have further showed that this treatment reduces VEGF level and angiogenesis in the lesion . We showed that treatment with rPEDF eradicates endometrial lesions as well as causes a significant decrease in the level of VEGF in the lesions.…”