updated 3/10/2004 6:15:35 PM ET 2004-03-10T23:15:35

Scientists say they’ve found stem cells in mouse ovaries that apparently generate new eggs well into adulthood, challenging nearly a century of biological dogma about fertility in mammals — including humans.

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If similar ovarian stem cells are found in women, researchers say it could lead to improved infertility and menopause treatments and possibly trigger a revolution in research into reproduction and women’s health.

And if the stem cells were shown to decline at a certain rate, it might help explain why women’s fertility drops as they approach 40.

However, researchers cautioned the finding does not guarantee similar human results. Even if women carried the cells, called germline stem cells, new therapies would take years to develop.

Findings could change understanding of fertility
“If these findings hold up in humans, all theories about female fertility and the aging of the reproductive system will have to be revisited,” said reproductive biologist Jonathan Tilly of Massachusetts General Hospital, who directed the mouse experiments.

The results are reported in Thursday’s issue of the journal Nature.

Other researchers who did not participate in the research said Tilly’s finding was remarkable, but it only opens a promising new line of inquiry.

“The big question — and it’s a big question mark — is whether this is relevant for human biology,” said Roger Gosden, the scientific director of the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School in Norfolk, Va.

The idea that women are born with a fixed number of eggs, or oocytes, was first suggested nearly a century ago, and Tilly said the subject had not been seriously broached in more than 50 years.

Among humans, mice and other mammals, females gradually lose healthy follicles — the tiny envelopes in which eggs develop and then burst. In older women, eggs often are abnormal, leading to a decline in fertility.

'The dogma must be wrong'
But oocyte research in female fruit flies showed that simpler species remained fertile throughout their adult lives and their ovaries never completely lose their germ stem cells. Despite obvious differences, fruit flies, mice and even humans share many genes and basic biological functions.

Tilly and his colleagues measured the number of healthy and dying eggs in juvenile and adult female mice. Initially, they found that the eggs died at a low but steady rate.

However, once the female mice reached early adulthood, the number of dying eggs accelerated to about one-third of the estimated 3,000 or so total follicles in each ovary, and the ovaries flushed out the dead eggs every few days.

At that pace, the researchers expected to see the animals’ oocytes depleted in a matter of days or weeks. Yet past work had shown that female mice remain fertile through at least one year of age.

As older eggs die off in juvenile and adult mice, germ stem cells the researchers found in the rodent’s ovaries apparently generate new eggs — a process that had been thought to occur only as female mammals developed in the womb.

“That’s when it really struck us that the dogma must be wrong. That sort of set off the bells and whistles,” said Tilly.

No guarantees for humans
Further research revealed the presence in the mice of a specific gene involved in creating new egg cells. Evidence of new eggs forming was also found in genetically altered adult mice implanted with ovarian tissue from normal females from the same litter.

Dr. Daniel Stein, medical director of in vitro fertilization at St. Luke’s-Roosevelt Hospital in New York, called the new research compelling. But he said that if egg-producing germ cells are found in women there is no guarantee they could be harnessed to postpone menopause or restore fertility, either in older women or women who suffered infertility side-effects from cancer treatments.

In a commentary article in Nature, Allan C. Spradling of the Howard Hughes Medical Institute and Carnegie Laboratory in Baltimore, Md., wrote the depletion of germ stem cells with advancing age might explain “the reproductive decline seen in female thirtysomethings.”

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