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

Abstract

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.

Effect of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogels on frozen‐thawed human ovarian tissue in a xenograft model

“…Several studies reported the positive effects of bFGF on angiogenesis and follicular survival in autograft and xenograft models, even though the total dose of bFGF (100–150 ng/mL for in vitro pretreatment, total 90–750 ng for in vivo administration via subcutaneous injection of free form or local transplantation with ovarian tissues using fibrin hydrogel or basement membrane extract) was much lower in these studies than in the present study (total 100 μg). However, it was not clear what was the actual dosage of active form of bFGF in vivo because there was no information about the in vivo release of bFGF.…”

“…Recently, various angiogenic growth factors have been evaluated for inducing neovascularization of fresh and frozen‐thawed ovarian grafts in autograft and xenograft animal models. Basic fibroblast growth factor (bFGF), which is one of the major regulators of angiogenesis, plays important roles not only in new vessel formation, but also in the modulation of vascular epithelial growth factor (VEGF) expression and upregulation of both FGF and VEGF receptors .…”

The blood vessels development, morphogenesis and blood circulation are three ontologic groups highly up-regulated in porcine oocytes before in vitro maturation

“…Moreover, in addition to mediation of endothelial cells angiogenic process, studies with human ovarian microvascular endothelial cells (hOMECs) proved that VEGFA promote endothelial cell migration [7]. Li et al (2016) indicate improved quality and survival rate of subcutaneously-transplanted mouse ovarian tissue in VEGF coupled with FGF2-treated subjects [8]. Furthermore, IVM of bovine oocytes supplemented with VEGF results in an improvement of cytoplasmic maturation, with a positive impact on oocyte developmental capacity [9].…”

Effect of treatment with angiopoietin-2 and vascular endothelial growth factor on the quality of xenografted bovine ovarian tissue in mice

“…The exact half-life of VEGF 164 used in this study is not known, but VEGF is known to have short half-life [ 34 ]. Even though VEGF has short half-life, it shows its angiogenic effect in previous studies [ 35 – 37 ]. Since the half-life of Ang-2 seems longer than that of VEGF, injection timing before XT was determined based on the half-life of Ang-2 being 18 hours, and the angiogenic factors were injected once again before the XT procedures.…”