Sphingosine-1-phosphate suppresses cyclophosphamide induced follicle apoptosis in human fetal ovarian xenografts in nude mice

ObjectiveTo investigate the antiapoptosis effect of sphingosine-1-phosphate (S1P) on human fetal ovarian tissue treated by cyclophosphamide (CTX).DesignExperimental animal study.SettingUniversity center for reproductive medicine and IVF unit.Animal(s)Female immunodeficient BALB/c nude mice, 6 to 8 weeks old.Intervention(s)Human fetal ovarian tissue slowly cryopreserved then subcutaneously transplanted in immunodeficient mice.Main Outcome Measure(s)Follicle survival assessed qualitatively and quantitatively using H&E staining, and cellular apoptosis of the ovarian grafts evaluated using transmission electron microscopy and DNA nick end labeling in situ (TUNEL assay).Result(s)The alkylating agent CTX caused a substantial follicle loss and apoptotic DNA fragmentation in the ovarian grafts in a period of 2 weeks of transplantation. The S1P treatment significantly prevented follicular apoptosis and maintained primordial follicle population in the grafts.Conclusion(s)This study shows for the first time that S1P protects primordial follicles in human ovarian grafts from a chemotherapy drug treatment via suppressing follicle apoptosis.