VEGF and bFGF increase survival of xenografted human ovarian tissue in an experimental rabbit model

Abstract

The aim of this study is to determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) could increase the survival of xenografted human ovarian tissue in an experimental rabbit model. Fresh human ovarian tissue was xenotransplanted into the back muscle of 25 castrated female New Zealand rabbits for 6weeks with the immunosuppression of FTY720 (2mg/kg/d). Rabbits were randomly divided into five experimental groups: (A) graft and host treatment with VEGF (50ng/ml); (B) graft and host treatment with bFGF (100ng/ml); (C) graft and host treatment with VEGF(50ng/ml) + bFGF (100ng/ml); (D) graft and host treatment with normal saline; (E) control group, no treatment. 4weeks after transplantation, human menopausal gonadotropin (HMG) 10IU was administered every second day in group A, group B, group C and group D for 2weeks. Graft survival was assessed by graft recovery rate, histological analysis, immunohistochemical staining for CD31 and Ki-67expression, TUNEL assay. After 6weeks of grafting, the number of CD31-positive stained cells increased significantly in group A, group B and group C compared to the control group. All groups showed strong Ki-67 immunostaining in ovarian stroma. Only one rabbit in group C retained the grafts' follicles. Grafting resulted in relative lower fibrosis in group A and group C compared to the control group. Apoptosis was significantly lower in group C compared to the control group. Fresh human ovarian cortex grafted into the back muscle of rabbit can sustain part of ovarian tissue function with the immunosuppression of FTY720, although follicle number diminishes significantly after grafting. The administration of VEGF and bFGF, especially the combination of them, may trigger angiogenesis, reduce apoptosis and fibrosis, increase survival in transplanted human ovarian tissue.