Women May Not Have Fixed Number of Eggs

Mouse study could lead to breakthroughs in infertility treatments

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HealthDay Reporter

WEDNESDAY, March 10, 2004 (HealthDayNews) -- In a new study that challenges one of the most basic tenets of reproductive biology, researchers say they've found that ovaries in mice don't contain a fixed number of eggs at birth.

This finding clashes with current scientific dogma that says most female mammals are born with a finite set of eggs, and once that supply is depleted menopause follows.

"The current thinking on how ovaries are formed and how they fail is wrong," says study author Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston. "The number of oocytes (egg cells) is not fixed at birth, but is renewing during adults' life."

Tilly says what most excites him about the finding is its implications for future research. "We now have in our hands a new set of biological and clinical questions," he says. "Given that the dogma is wrong, we have to begin to rethink the aging process in females and how that process is regulated."

"We also may need to revisit the mechanisms underlying such environmental effects on fertility as smoking, chemotherapy and radiation. Eventually, this could lead to totally new approaches to combating infertility in cancer patients and others," adds Tilly, an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School.

The study appears in the March 11 issue of Nature.

In a second study in the journal, researchers announced the birth of a rhesus monkey produced using transplanted ovarian tissue.

Tilly and his research team were looking for ways to stop cell death during radiation or chemotherapy treatment for cancer. To assess the affects of these treatments on egg cells, the researchers needed to measure the number of follicles (the sacs in which eggs grow to maturity) normally found in healthy mice.

What they found surprised them. When the animals were young, they had a low level of dying follicles. As they aged, that number increased to about 1,200 follicles dying per day in each ovary. Since, the researchers only found 3,000 healthy follicles, a rate of 1,200 per day would quickly deplete the remaining follicles if no new follicles developed.

Because this finding contradicted commonly held beliefs, the researchers took a closer look at the makeup of the mouse ovaries. They carefully examined the outer surface of the ovaries and found germ cells, which, according to Tilly, are adult stem cells. These ovarian germ cells secreted a protein only found as oocytes are developing, suggesting that in mice, oocytes continue to be manufactured long after birth.

Tilly says he expects some initial skepticism to the idea that women may not have a fixed number of eggs. However, he hopes this finding will spur new areas of research in fertility and in aging.

In the second study, researchers said they were able to produce the birth of a rhesus monkey by using transplanted ovarian tissue.

"Our lab is trying to help develop strategies to preserve fertility in young women and children with cancer," says Dr. David Lee, an assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.

One way scientists hope to do this is by freezing a woman's ovaries before cancer treatment for use in reproduction later in life. To date, this has not been accomplished, although researchers from the Center for Reproductive Medicine and Infertility in New York City announced on March 8 that they'd been able to create a human embryo using frozen ovarian tissue.

For this study, Lee says, "We removed ovarian tissue [from seven monkeys] and transplanted it to distant sites, such as the arm or abdomen [in the same animals]." This tissue was never frozen.

Once transplanted, Lee explains, the tissue survived by diffusion, soaking up nutrients until it could establish its own blood supply. Eventually, the transplanted tissue produced eight mature eggs, which were harvested. Six were fertilized with sperm. Two developed into embryos, which were implanted into two surrogate mother monkeys. One healthy pregnancy and birth resulted.

Of both studies, as well as other research that's ongoing, Lee says, "there's really a confluence of very exciting research all at the same time, and all offer hope for fertility."

More information

To learn more about preserving fertility in young people with cancer, visit the American Cancer Society. The society also offers this article on fertility for adults undergoing cancer treatment.

SOURCES: Jonathan Tilly, Ph.D., director, Vincent Center for Reproductive Biology, Massachusetts General Hospital, and associate professor, obstetrics, gynecology and reproductive biology, Harvard Medical School, Boston; David Lee, M.D., assistant professor, obstetrics and gynecology, division of reproductive endocrinology, and assistant professor, pediatrics, Oregon Health and Science University, Portland; March 11, 2004, Nature

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