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

Objective: To investigate the antiapoptosis effect of sphingosine-1-phosphate (S1P) on human fetal ovarian tissue treated by cyclophosphamide (CTX). Design: Experimental animal study. Setting: University 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. (C) 2014 by American Society for Reproductive Medicine.