采用基础成纤维细胞生长因子与纤维蛋白水凝胶改善异位同种异体移植小鼠卵巢组织的质量

Abstract

STUDY QUESTIONDoes basic fibroblast growth factor (bFGF) in combination with fibrin hydrogel improve follicle development and revascularization of heterotopically transplanted mouse ovarian tissues?SUMMARY ANSWERTreatment of transplanted ovarian tissues with higher concentrations (75, 100 and 150 μg/ml), but not lower concentrations (25 and 50 μg/ml), of bFGF significantly improved primordial follicle survival and angiogenesis, while apoptosis of follicles and stromal cells was significantly decreased.WHAT IS KNOWN ALREADYUse of transplanted ovarian tissues in female fertility preservation is limited by the massive loss of follicles and ischemia-reperfusion injury due to the expected delay in revascularization.STUDY DESIGN, SIZE AND DURATIONOvarian tissues from 18-day-old ICR mice were encapsulated in brin hydrogel mixed with different concentrations of bFGF, then transplanted under the skin of adult female mice for 1 week. The ovarian tissues treated without fibrin hydrogels and bFGF were designated as Control group I, and the ovarian tissues treated with fibrin hydrogels but without bFGF were designated as Control group II. The ovarian tissues treated with 25 and 50 μg/ml bFGF were designated as the lower concentration group, and the ovarian tissues treated with 75, 100 and 150 μg/ml bFGF were designated as the higher concentration group.MATERIALS, SETTING AND METHODSAssessment of follicular quantity and follicle classification was carried out by histologic analysis. Follicle proliferation was evidenced by immunostaining with proliferating cell nuclear antigen and apoptosis was verified by anti-active caspase-3 staining. Epithelial cells of new blood vessels were stained using CD31 antibody to evaluate neoangiogenesis, and the blood vessel density was analyzed by immunohistochemistry.MAIN RESULTS AND THE ROLE OF CHANCEThe ovarian tissues were recovered 1 week post-transplantation. Compared with the control group, the survival and proliferation of the follicles was significantly increased, the apoptosis of follicles and stromal cells was significantly decreased, and angiogenesis was significantly enhanced when the transplanted ovarian tissues were treated with a higher concentration of bFGF. Treatment with a lower concentration of bFGF did not improve follicle survival and blood revascularization.LIMITATIONS, REASONS FOR CAUTIONThe results obtained may not be fully extrapolated to humans because of the physiologic differences between mice and humans.WIDER IMPLICATIONS OF THE FINDINGSFor the first time, the present study investigated the role of bFGF in transplanted ovarian tissues and demonstrated that bFGF might significantly improve the quality of transplanted ovarian tissues by increasing follicle quantity and promoting neoangiogenesis. This study sets the stage for further study and application of ovarian tissue transplantation in clinics, and may eventually benefit females for fertility preservation.