American scientists have preserved ovarian function and fertility in female mice after radiation treatment using the compound sphingosine-1-phosphate (S1P). They also found that fertility can be preserved without genetic damage in the offspring of the irradiated mothers.
‘Sterility is a routine side-effect of chemotherapy and radiation in young women treated for cancer. These studies show that S1P could possibly be converted into a drug that might be effective in preventing sterility,’ says Richard Kolesnick , lead researcher and head of the Laboratory of Signal Transduction at the Memorial Sloan Kettering Cancer Center, New York.
‘We can cure many children with cancer but unfortunately they become sterile after exposure to chemotherapy and radiation, and there are no pharmacological or other therapies to prevent this catastrophic problem,’ Kolesnick adds.
Zvi Fuks, one of Kolesnick’s collaborators and expert on radiation effects, explains that women exposed to radiation in the pelvic area at any time before menopause can become sterile.
Until recently, it was thought that preservation of oocytes might lead to genetic damage in future generations, and the deletion of DNA-damaged oocytes after radiation therapy of chemotherapy could preserve genomic integrity. ‘But our studies indicate that sterility can be preserved, and the oocytes that remain are not genetically dangerous for the offspring,’ says Fuks.
Apoptosis begins in oocytes when ceramide (a lipid) is produced in response to radiation or chemotherapeutic agents. S1P, a metabolite of ceramide, blocks this process, and the oocytes never receive the signal to apoptose.
Kolesnick and team’s experiment included mating female mice treated with radiation therapy and S1P with normal males. The S1P-treated mothers delivered normal litters, and the offspring had no significant phenotypic, anatomical, behavioural, histological, haematological, or biochemical abnormalities. Subsequent generations were also normal.
The researchers also analysed the oocytes of the irradiated mothers, and found no significant damage. Future generations were also evaluated for DNA damage, and found no difference between these and non-irradiated age-matched controls. Nevertheless, these findings do not exclude the possibility of genetic damage in much later generations, the researchers said.
‘What this research suggests is that when using an S1P-based pharmacological approach, it might be possible one day to preserve ovarian function without propagating genetic damage,’ comments Kolesnick, but there is still much more research that needs to be done. ‘This is still translational research, and there’s a lot of work left to do before we try clinical application.’
(Source: The Lancet Oncology Journal)