Optimal FSH usage in revascularization of allotransplanted ovarian tissue in mice.

BACKGROUD: Ovarian transplantation is a useful method for preserving the fertility of young women with cancer who undergo radiotherapy and chemotherapy. Follicle-stimulating hormone (FSH) is use to protect transplanted ovarian tissues from ischemia injury through promoting revascularization after transplantation, but the side effect of high level FSH is ovarian overstimulation leading to substantial follicular loss. In this study, we investigated the optimal usage of FSH on revascularization in the in vitro cultured ovarian tissues before and after transplantation. RESULTS: FSH mainly exhibited an additive response in the gene and protein expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and follicle stimulating hormone receptor (FSHR) with its raised concentrations (0.15 IU/ml, 0.30 IU/ml and 0.60 IU/ml) and prolonged treatment (3 h, 6 h, 12 h, 24 h). The concentrations with 0.60 IU/ml FSH could obviously promoted the expression of VEGF, bFGF and FSHR, but under this concentration FSH could also overstimulated the ovarian tissue leading to follicular loss. With the increase of culture time, the gene and protein expression of VEGF and bFGF both were up-regulated in all of the FSH added groups, but FSHR expression decreased when culture time exceeded 12 h. So we chose 0.30 IU/ml FSH added concentration and 6 h culture time as the FSH usage condition in functional revascularization verification experiment, and found that under this condition FSH promoted 2.5 times increase of vascular density in treated group than in control group after ovarian tissues transplantation. CONCLUSION: Ovarian intervention with 0.30 IU/ml FSH for 6 h is an optimal FSH usage condition which could accelerate the revascularization in the allotransplanted ovarian tissue and can not produce ovarian overstimulation.

Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats.

BACKGROUND: Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen. METHODS: Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods. RESULTS: Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group. CONCLUSIONS: The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal sperm.