Long live the ovary: Mutant mice keep eggs.

It's among the most wasteful phenomena in the human body. A female starts her life with millions of immature eggs, or oocytes, in her ovaries. Yet over the years, most of those cells commit suicide, eventually leaving the ovaries barren.

A similar squandering occurs in many mammals, but researchers have now found that a gene mutation can thwart this process in female mice. When they lack normal copies of the gene called BAX, aged rodents--the equivalent of women 100 to 120 years old--retain the egg-filled ovaries of a young mouse.

"Not only can a [mutation in a] single gene protect a large number of egg cells, it can actually prolong ovarian life span in mice," says Jonathan L. Tilly of the Massachusetts General Hospital in Boston.

Tilly and his colleagues describe the seemingly healthy, mutant mice in the February NATURE GENETICS. With age, the animals still become infertile, the researchers find, presumably because their brains stop sending hormones that command the ovary to release mature eggs, or ovulate. "Apparently, the neuroendocrine system that drives the ovaries is not functioning," says Frank Bellino of the National Institute on Aging in Bethesda, Md.

Artificial means, however, can jumpstart the elderly ovaries of the mutant mice. Tilly's group showed that the injection of a hormone that normally triggers ovulation stimulates 20-to-22-month-old mice to release mature eggs into their oviducts. When fertilized by sperm, the eggs begin to divide as expected. The researchers are now testing the quality of the aged eggs by fertilizing them and then implanting them in surrogate mothers.

The gene mutated by Tilly's group encodes a protein employed by oocytes when they start to commit suicide. Its absence appears to stop such egg cell death.

While this research may one day suggest means of extending a woman's fertility, Tilly is more concerned with preserving a woman's overall health. Throughout their egg-bearing lives, ovaries secrete hormones such as estrogen that ward off heart disease, osteoporosis, and other illnesses. That's why after menopause, which coincides with the ovaries running out of eggs, many women undergo estrogen replacement therapy.

If scientists could learn how to make ovaries survive longer, they might improve on such treatments. In addition to estrogen, "there may be other things coming from the ovaries that are also beneficial to the body that we're just not aware of yet," notes Tilly.

"Until now, there's really been no animal model to test whether or not sustained ovarian function would truly have a beneficial impact on any parameter--bone mass, heart function, et cetera."

"This is a very hot area," says oocyte investigator John J. Eppig of the Jackson Laboratory in Bar Harbor, Maine. "A lot of people view the idea of regulating [ovarian] development as a potential way of prolonging female health. In theory ... you could delay the onset of menopause."

Bellino notes that Tilly's mutant mice may shed light on whether menopause is triggered solely by the ovaries or whether the brain's hormonal signals also play a role. Noting that BAX's protein is missing in all the tissues of the mice, not just the ovaries, Bellino cautions that "one doesn't know how that particular property is affecting the observations." Consequently, he says, it's unclear how the mutant mice compare with normal mice and with people.