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

Abstract

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.

Keywords: Apoptosis; cyclophosphamide; ovarian tissue cryopreservation; ovarian tissue transplantation; sphingosine-1-phosphate.