VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues

Int J Mol Sci. 2016 Jul 30;17(8):1237. doi: 10.3390/ijms17081237.


This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue.

Keywords: angiogenic factor; fertility reservation; oocyte quality; ovarian cryopreservation; ovarian transplantation.

MeSH terms

  • Animals
  • Blastocyst / cytology*
  • Blastocyst / drug effects
  • Cell Survival / drug effects*
  • Cryopreservation
  • Embryonic Development / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fertilization in Vitro
  • Fibroblast Growth Factor 2 / pharmacology*
  • Immunoenzyme Techniques
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Ovary / cytology*
  • Ovary / drug effects
  • Subcutaneous Tissue
  • Transplantation, Autologous
  • Vascular Endothelial Growth Factor A / pharmacology*


  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2