Study Of Effects Of BFGF On The Recovery Of The Spermatogenic Damage Induced By Cyclophosphamide In Mice

Objective:To investigate the repairing effects of bFGF on the cyclophosphamide-induced damage of spermatogenesis and explore the correlative mechanisms.Methods:1.Establishment of the mouse model of the chemotherapy-induced damage of spermatogenesis:70 male mice were randomly divided into two groups:the normal control group (n=20), the model group (n=50). The model group was given cyclophosphamide by intraperitoneal injection at a dose of 5 mg/Kg body weight once a day for 36 days. The normal control group was injected intraperitoneally with saline at the same volume. The 10 mice of each group were sacrificed 24h after the last cyclophosphamide treatment. The correlative targets were measured. It had been proved that the mouse model of the chemotherapy-induced damage of spermatogenesis was successful.2. bFGF treament:In addition to the normal control group,40 mice of the model group were randomly divided into 4 groups:the model control group, the low-dose group, the middle-dose group, the high-dose group. The low-dose group, the middle-dose group and the high-dose group were respectively injected intraperitoneally with bFGF at a dose of 400IU/Kg,800IU/Kg,1200IU/Kg body weight once a day for 36 days. The other groups were given saline at the same volume by intraperitoneal injection.3. Detection of the targets:Blood of all the mice was collected 24h after the last bFGF treatment, then all the animals were sacrificed. By light microscope, electron microscope, immunohistochemistry and radioimmunoassay methods, the following targets were measured:1.Measure of the testicular and the epididymal somatic index,2. Histological study of the testises,3. Observation of the testicular ultrastructure,4. Estimation of the semen quality,5. Assay of the testicular PCNA expression,6. Assay of the plasma lutuneizing hormone, follicle-stimulating hormone, and testosterone.4. Statistical analysis:All data were analyzed by one-way ANOVA.Results:1. The repairing effects of bFGF on the cyclophosphamide-induced damage of spermatogenesis:As compared with.the normal control group in the model control group, the testicular and epididymal somatic index, the sperm count, the sperm motility and the sperm survival rate were decreased significantly, while the sperm malformation rate was increased significantly. Besides, there were the significant pathological changes in the testicular histology and the ultrastructure. Compared with the model control group, the above targets were significantly improved in the low-dose group, the middle-dose group, and the high-dose group. Those targets in the middle-dose group and the high-dose group were restored to the level of the normal control group. There was significant differentiation between the low-dose group and the normal control group concerning all the above targets.2. The correlative mechnisms of the repairing effects of bFGF on the cyclophosphamide-induced damage of spermatogenesis:The number of cells expressing PCNA and the level of serum testosterone, lutuneizing hormone and follicle-stimulating hormone were both decreased significantly in the model control group compared with the normal control group. But compared to the model control group, the data mentioned above were increased significantly in the low-dose group, the middle-dose group, and the high-dose group.Conclusions:1. bFGF exerts significant repairing effects on the cyclophosphamide-induced damage of spermatogenesis, so as to provide the experimental evidence for the clinical prevention and treatments of the chemotherapy-induced damage of spermatogenesis.2. The possible mechnisms are that bFGF may play important roles in the stimulatory regulation of the proliferation and differentiation of spermatogenic cells, and have the specific stimulatory effects on secretion of testosterone, lutuneizing hormone and follicle-stimulating hormone by regulating the hypothalamic-pituitary-gonadal axis.