title: Effect of Local Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor on Subcutaneously Allotransplanted Ovarian Tissue in Ovariectomized Mice.
abstract: OBJECTIVE
  One of the major obstacles to ovarian tissue preservation is delayed angiogenesis that leads follicles lost after transplantation. The aim of the present study was to investigate the effects of bFGF and VEGF on heterotopic transplanted ovarian tissue using a mouse model.
  
  
  METHODS
  Female mice underwent bilateral ovariectomy. Ovarian tissues encapsulated by fibrin hydrogels were transplanted subcutaneously into recipient mice, in which ovarian hormonal cyclicity was absent. The fibrinogen solution was mixed with bFGF, VEGF, or a mixture of bFGF and VEGF. The grafts were recovered 21 days after transplantation. Follicle morphology and follicle numbers were observed by H&E staining. Blood vessels were observed in transplanted intra-ovarian tissue by CD31 antibody IHC staining. Daily vaginal cytology was performed to determine estrous cycle and functional restoration of transplanted ovarian tissue. Blood was collected weekly and serum FSH levels were measured with a radioimmunoassay kit. Apoptosis analysis was performed by anti-AC-3 staining and survivin mRNA expression.
  
  
  RESULTS
  The number of primordial follicles and secondary follicles in the bFGF+VEGF group was significantly higher than in the control group. The vascular density in the bFGF+VEGF groups were significantly higher than in the bFGF and the VEGF groups; there was no significant difference between the bFGF and VEGF groups. Estrous cycle was earlier in the bFGF+VEGF group compared with the control group; all mice in this group restored ovarian function. Serum FSH levels in the bFGF+VEGF group were significantly lower than in the control group by day 14 post-transplantation. The AC-3-positive in control group was significantly higher compared with bFGF group and VEGF group, and in bFGF+VEGF group was significantly lower than bFGF group and VEGF group. Survivin mRNA expression in bFGF+VEGF group was significantly higher than control group.
  
  
  CONCLUSIONS
  The combination of bFGF and VEGF has beneficial effects on follicle survival, angiogenesis, and resumption of estrous cycles.
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Jiangman
authors.initials: J
authors.lastname: Gao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Hongcui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000818:Animals; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects* / Q000637:transplantation; D010052:Ovariectomy; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2