October 13, 2000

A team of scientists from the MGH 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 ceramide, 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. He notes, however, that further research needs to be completed before trials of S1P could be attempted in human patients.

It has been known that chemotherapy and radiation therapy can accelerate the death of oocytes, resulting in premature menopause and infertility. 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 signals called ceramide, Bax and caspase-2.

The current experiments – conducted by Yutaka Morita, MD, PhD, and Gloria Perez, DVM, PhD, of the MGH – showed that injecting S1P into the ovaries of female mice before they were exposed to radiation protected the ovaries from damage. Oocytes from the protected ovaries developed into eggs capable of normal fertilization and development.

"In this study, we targeted ceramide and S1P because they work at the very earliest steps of the cell-death process," Tilly explains. "From a biological standpoint, the earlier we can head off cell death signaling, the healthier the cell will be. We're very gratified to see this theory supported in living animals."