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Female Mice Produce Eggs throughout Their Lives

By Cheryl Simon Silver

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Stem Cells

Arrows point to reproductive stem cells in a mouse ovary.
Every woman grows up believing she won’t be able to bear children late in life. Researchers believe the same, and the textbooks all say that women are born with a finite supply of eggs that goes bad with age. Now, a new study in mice is challenging this basic tenet of reproductive biology.

Scientists have discovered that female mice produce eggs throughout their lives, replenishing their supply on a daily basis. The key to this process is a special kind of “stem cell” that is the precursor to an egg.

By studying the mice, the researchers concluded that problems with reproduction late in life may have more to do with the supply of reproductive stem cells than with the eggs.

Similar stem cells may be present in the human ovary, and the possibility raises hope for new approaches to fertility treatment. In theory, new stem cells could be implanted into women to rejuvenate an ovary compromised by cancer treatments or by the natural aging process. But first researchers need to find the stem cells themselves in the human ovary.

Researchers at Massachusetts General Hospital and Harvard Medical School in Boston report their findings today in Nature. They describe a series of experiments, conducted over two years, to prove to themselves and now to others what they had found.

The study at first was unexceptional. The scientists were measuring changes in the numbers of healthy egg cells from birth through adulthood. They found that by adulthood, an animal’s egg cells and the supporting cells declined by about 30 percent.

Then they discovered, quite unexpectedly, that this rate persisted. If eggs were destroyed at this rate and not replenished, then the species would likely die off.

“If one third of a fixed pool of anything is going away, the lifetime of that population won’t be very long,” says Jonathan Tilly of Massachusetts General Hospital, who led the research. “Given the dogma that existed, that didn’t make any sense.”

At first the scientists regarded the finding with disbelief. They thought perhaps the pool of dying egg cells had simply built up over time. Two different experiments showed the same result, however. The dying egg cells were cleared out within three days.

“By simple multiplication, the ovaries wouldn’t last two weeks if the dogma were true,” Tilly says. “It was a shock, but you can’t argue the numbers. Something was going on that everyone had missed.”

The answer turned out to be that new eggs were being produced as the old ones were being discarded.

The idea that female mammals can renew their eggs throughout life fits with what is known about other organisms. In the fruit fly, both male and female flies retain reproductive stem cells throughout their lives and are fertile at any age. And male mammals produce viable sperm through adulthood.

As Tilly points out, there would be no reason for mammals to evolve away from the ability to refresh the pool of eggs.

So what are the origins of this remarkably robust scientific dogma? The source is not known, though it likely comes from early in the last century. In 1951, however, biologist Solly Zuckerman conducted a number of tests on ovarian tissue and eggs. He concluded that yes, the number of eggs peaks at birth, and declines with age until menopause.

No one challenged that assertion for more than a half century. Until now.

Tilly, J. et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428, March 11, 2004.

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