Abstract
ObjectiveOne 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.MethodsFemale 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.ResultsThe 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.ConclusionThe combination of bFGF and VEGF has beneficial effects on follicle survival, angiogenesis, and resumption of estrous cycles.
Highlights
In women, approximately one tenth of cancers occur in
The vascular density in the basic fibroblast growth factor (bFGF)+Vascular endothelial growth factor (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
Summary
More than 90% of girls and young women with cancer require chemotherapy, radiotherapy, or bone marrow transplantation for curative treatment[1]. The gonadotoxicity of ionizing radiation and chemotherapeutic drugs can frequently lead to premature ovarian failure (POF) and loss of endocrine and reproductive function, conditions with serious long-term hormone-related consequences and infertility. The severity of these effects depends on follicular reserve, patient age, and the type and dose of drugs used. Compared with the cryopreservation of oocytes and embryos, ovarian tissue cryopreservation requires neither a sperm donor nor ovarian stimulation, which would be appropriate for women who require immediate cancer treatment or who have contraindications for ovarian stimulation. The overall pregnancy rate after transplantation of ovarian tissue has been estimated to be between 11% and 30% [2]
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