Ovarian failure and infertility are common side effects for women who undergo radiation and chemotherapy. In most mammals, the entire oocyte supply is created during embryonic development, and as many as 80 percent of the oocytes die before birth. Oocytes that remain are extremely sensitive to agents used in cancer treatment, which trigger apoptosis.

"Unfortunately, there are no pharmacological or other therapies to prevent this catastrophic problem," said Richard Kolesnick, M.D., lead author of the study. Zvi Fuks, M.D., a collaborator and an expert on radiation effects, explained that women, from birth to menopause, are likely to become sterile if the ovaries are exposed to radiation during treatment for cancer.

Apoptosis begins in oocytes when a lipid termed ceramide is produced in response to radiation or drugs. The experimental compound works by blocking ceramide action --- the oocytes never receive the signal that triggers apoptosis.

Two months after treating the female mice with radiation, the researchers mated them with normal males. In an unexpected finding, drug-treated mothers delivered normal litters, and the offspring appeared normal by several criteria. Furthermore, subsequent generations also appeared normal. Nevertheless, the appearance of normality does not exclude the possibility of genetic damage that might be expressed in later generations.

"The ability to prevent sterility may not be desirable," Dr. Kolesnick says. The current concept of oocyte deletion after radiation or drug exposure suggests that organisms eliminate damaged oocytes to protect the genome of the offspring. "We had to ask ourselves, 'Are we now preserving the most damaged oocytes?' "

To address the question of whether there were genetic abnormalities in the irradiated mothers' oocytes, the researchers retrieved oocytes from the mothers treated with both drug and radiation; they found no significant damage. Then they checked the progeny to see if any genetic damage had occurred and similarly failed to find any abnormalities.

"What this research suggests," according to Dr. Kolesnick, "is that, when using an S1P-based pharmacological approach, it might be possible to one day preserve ovarian function without propagating genetic damage."

The discovery provides hope for women who undergo cancer treatments and want to preserve their fertility. "But," Dr. Fuks adds, "this is still translational research, and there is still much work to be done." Further research is being planned, he said.