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अमूर्त

Sphingosine-1-Phosphate may Decrease the Cytotoxic Effect of Doxorubicin on Human Granulosa Cells

Orli Turgeman, Ilan Calderon, Martha Dirnfeld, Mada Hashem and Zeev Blumenfeld

Context: The increase in malignancy of young women in the recent decades, combined with a significant improvement in long term survival after gonadotoxic chemotherapy, have brought about a ubiquitous interest in preservation of fertility in these young patients. The present study examines the effects of Sphingosine-1-Phosphate (S1P) on primary human granulosa cell cultures in-vitro as a possible protecting factor against Doxorubicin (DOX) and Cyclophosphamide associated toxicity. Understanding cytotoxic effects and gonadotoxicity in human luteinized Granulosa Cells (GC) may contribute to our understanding and preventing follicle loss.

Study objective: To examine the possible protective effect of S1P on chemotherapy induced gonadotoxicity, in human luteinized Granulosa Cells (GCs).

Design: Human GC’s were donated by women undergoing follicular aspiration for in vitro fertilization (IVF), after informed consent and institutional approval by ethics committee (IRB, Helsinki). The GCs were separated from RBC’s by centrifugation on ficoll and plated on multiwell plates for Lactate Dehydrogenase (LDH) assay, and on 6 well plates for flow cytometry. Each experiment was conducted in triplicates and repeated at least three times.

Results: S1P significantly protected GCs against Doxorubicin (DOX) toxicity, but inconsistently against Cyclophosphamide.

Conclusion: S1P may minimize the gonadotoxic effect of chemotherapy on human luteinized granulosa cells.