PNNL

Abstract

Although fertility preservation in female cancer patients is of tremendous clinical interest, cryopreservation of oocytes and ovarian tissue are the only options currently offered. In rodents, sphingosine-1-phosphate (S1P) shields the ovaries from damage caused by anti-cancer treatments, allowing for retention of long-term fertility. Here we report that S1P exerts similar protective effects in ovaries of adult female rhesus macaques exposed to 15 Gy of radiation. Further, monkeys given the long-acting S1P mimetic, FTY720, before ovarian irradiation rapidly resume menstrual cycles and become pregnant in mating trials. Offspring conceived and delivered by radioprotected females develop normally, and show no evidence of genomic instability as measured by micronucleus frequency in blood reticulocytes. Pre-exposure of adult human ovary tissue xenografted into mice with S1P also reduces radiation-induced primordial oocyte depletion. Thus, S1P and its analogs hold considerable clinical promise as fertility preservation agents.