癌の放射線療法や化学療法から卵巣を守る　

2000/10/4　マウスの実験で卵巣を SIP(sphingosine-1-phosphate) を入れた袋で被い放射線照射を行った結果、卵の障害を防げたという。抗癌剤投与に対しても防御効果があると考えられており、ヒトの女性の癌治療により閉経が早まることを防ぐことができると期待されている。
Staying Fertile after Cancer Treatment
By Nicolle Charbonneau
HealthSCOUT Reporter
WEDNESDAY, Oct. 4 (HealthSCOUT) -- Scientists may have found a way to protect the fertility of women who must undergo radiation or chemotherapy.
These treatments for cancer often destroy a woman's ovaries, bringing on early menopause and dashing hopes of becoming pregnant.
But researchers in Boston say that tests on mice show that a compound injected into the sac that surrounds the ovaries protected them from normally lethal doses of radiation. The mice remained fertile, later producing normal-sized litters.
If the technique works in people as well, it could help others besides cancer patients, the researchers say. It also could have the potential to delay menopause in healthy women, allowing them to have children at a later age, the say.
Women normally lose egg cells throughout their lives, says Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital. He says the drop-off begins immediately, starting from about 7 million eggs in a female fetus halfway through gestation and falling to 1 million at birth, then to 300,000 by puberty and continuing to decline until only about 1,000 remain, which triggers menopause.
Known as apoptosis, this process of programmed cell death involves a series of chemicals, Tilly says. Early in the process, a molecule in the body called sphingomyelin is converted into the chemical ceramide, and the researchers suspected that preventing ceramide from working might stop the cell death in its early stages.
To test this theory, the researchers injected a compound known as S1P (for sphingosine-1-phosphate) into the sac surrounding each ovary in one group of mice. Two hours later, they exposed the ovaries to a high dose of radiation, enough to destroy 80 percent of the egg cells under normal conditions.
"There were no side effects that we could discern," Tilly says.
The researchers injected only one ovary in a mouse, leaving the other ovary unprotected from the radiation.
"Only the treated [ovary] within the same animal was protected, which tells us that the S1P molecule did not diffuse throughout the body," Tilly says.
In the group of mice that did not receive injections, half were unable to conceive, "which is consistent with damage to ovaries," Tilly says. But in the group that did get the injection, he says all of the mice retained their eggs and were able to become pregnant and produce healthy litter sizes. Findings appear in the current issue of Nature Medicine.
Although the research focused on radiation only, Tilly says that other test results indicate that S1P also would protect ovaries from chemotherapy.
To find out whether it will work on human ovaries, Tilly now is testing the process on mice that have been genetically engineered to grow human ovaries, providing egg cells at many stages of maturity. If it works on these animals, Tilly says, the next step could be testing on people, although he won't speculate on how far in the future that might be.
Dr. Edward Trimble, head of the surgery section at the National Cancer Institute's Cancer Therapy Evaluation Program, says the research "both helps us understand why cells in the ovary die because of these treatments, as well as point out how we might potentially intervene."
Radiation or chemotherapy "has a great impact on the fertility of cancer patients after they've been treated for their cancer, [and it] puts them at risk for adverse health outcomes associated with premature menopause," Trimble says.
Tilly says the findings might have application beyond cancer patients, delaying not just premature but regular menopause, for instance.
"It's certainly not out of the realm of possibility that S1P or related kinds of molecules could be used to prolong normal ovarian function past the time it ceases right now," he says.