Possible stem cells in ovaries prompt fertility boosting ideas.
Scientists have found hints that mammals' ovaries produce new eggs throughout life, a finding that might herald new treatments for infertility and the menopause.
The discovery challenges a decades-old dogma that women and other mammals are born with a limited supply of immature eggs. These were thought to be expended by decay, death or ovulation until, at menopause, the supply was exhausted.
Now US researchers have unearthed evidence in a mouse's ovary of stem cells that churn out fresh eggs during its reproductive years. This suggests ovaries have more in common with the male's testicular sperm factory than had been thought.
"We are still reeling," says Jonathan Tilly of Harvard Medical School, Boston, who led the Nature study1.
"It is a radical new way of thinking," says fertility pioneer Roger Gosden of the Jones Institute for Reproductive Medicine in Norfolk, Virginia. But it is not yet clear whether such stem cells exist in human ovaries, Gosden cautions, or how prolific they might be.
If researchers do find ovarian stem cells in women, it could overturn the way they think about fertility and the menopause.
It was thought that women's fertility declines with age because the number and quality of immature eggs they are born with deteriorate over time; by menopause, eggs have been hanging around for roughly 50 years.
Tilly's results suggest instead that there is continual birth and death of eggs. It may be that, with age, fewer or more defective eggs are produced because the stem cells are dying off or growing old.
It is a radical new way of thinking Roger Gosden , Jones Institute for Reproductive Medicine, Virginia
Tilly speculates that, in future, women might freeze their youthful ovarian stem cells for re-implantation and production of fresh eggs at a later age. Alternatively, researchers might find drugs that can revive flagging stem cells.
Such treatments would be valuable for cancer patients whose ovaries are damaged by drug therapy or for women who want to avoid the age-related drop in fertility or even reverse their menopause. If such treatments emerge, however, "they will be a very long way off," warns Gosden.
The doctrine that ovaries harbour a restricted pool of eggs stemmed from extensive examinations of ovarian tissue, many in the 1950s. These showed that the number of immature follicles, which contain eggs, declines throughout life. "Nobody ever questioned this before," says Gosden.
Tilly's team did - when experiments showed that up to a third of ovarian follicles are dying in young adult mice at one time and yet the supply does not dry up. This is hard to explain unless new eggs are being made to replace the vanishing ones. "That's when all the bells and whistles went off," says Tilly.
The group identified stem cell candidates on the outer surface of the ovary and, among other experiments, treated mice with a drug that paralyses stem cells. After three weeks, they found that the number of immature eggs in the mouse ovary shrank by 95% because they were no longer being replenished.
Tilly says he is now attempting to isolate the ovarian stem cells from mice and identify characteristic active genes within them. He will then search for potential stem cells with similar genetic signatures in biopsies of human ovaries.
Johnson, J., Canning, J., Kaneko, T., Pru, J.K. & Tilly, J.L. Nature, 428, 145 - 150, (2004).
Jones Institute for Reproductive Medicine, Virginia
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Pearson, H. Ovaries may lay new eggs. Nature (2004). https://doi.org/10.1038/news040308-6