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Treatment protects mouse ovaries from radiation therapy

Study may lead to ways to preserve fertility in women undergoing cancer treatment

A team of researchers from the Massachusetts General Hospital (MGH), Memorial Sloan-Kettering Cancer Center in New York, and other research centers has found a molecule that, in animal studies, has blocked the destruction of ovarian egg cells (oocytes) by radiation therapy. The report in the October issue of Nature Medicine describes how a compound called sphingosine-1-phosphate (S1P), which blocks the activity of a cell-death-associated molecule called ceremide, preserved ovarian egg cells and fertility in female mice exposed to levels of radiotherapy that otherwise would have destroyed their ovaries. The researchers expect that the same protection would be afforded to ovaries exposed to chemotherapeutic drugs.

"For the first time we have a promising prospect for a small molecule that could be given to women and girls undergoing cancer treatment to protect their ovaries," says Jonathan Tilly, PhD, the paper's senior author. However, he notes that further research needs to be completed before trials of S1P could be attempted in human patients.

All mammalian females are born with a huge supply of immature egg cells that is depleted throughout their lives by a process called programmed cell death or apoptosis. Only a tiny fraction of the oocytes a female is born with actually mature and are released from the ovaries as eggs. It has long been known that treatment with chemotherapy drugs and radiation therapy can accellerate the death of oocytes, resulting in premature menopause and infertility among many women and young girls who are treated for cancer.

In previous research, Tilly's team at the MGH Vincent Center for Reproductive Biology had shown that oocytes were destroyed by chemotherapy through a particular cell-death pathway involving the interaction of three principal signs called ceramide, Bax and caspase-2. They also showed that knocking out
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Contact: Susan McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
1-Oct-2000


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