Mark Henderson, Science Editor
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The theory that women are born with all the eggs they will ever have has been challenged by research that could raise the prospect of restoring female fertility and reversing the menopause.
Scientists in China have discovered that the ovaries of adult and newborn mice seem to contain stem cells that can be grown into eggs that can be fertilised to create healthy offspring.
The findings suggest that it may be possible one day to isolate and culture these stem cells from women’s ovaries, should they also exist in humans. This could provide a source of eggs to extend female fertility, which declines as the ovaries’ supply is depleted with age.
If work at Shanghai Jiao Tong University is confirmed, it would overturn a long-held principle of reproductive biology: that female mammals are born with all their eggs. Immature eggs either ripen and are ovulated or die off, until the supply is exhausted.
The research, however, is highly controversial and many scientists doubt whether the Chinese team has proved that its ovarian stem cells can give rise to functional eggs and mouse pups.
When Jonathan Tilly, of the Massachusetts General Hospital in Boston, made similar claims five years ago, other researchers struggled to replicate his findings.
Professor Robin Lovell-Badge, of the National Institute for Medical Research in London, said: “This paper will stimulate lots of activity in the scientific community, as happens when any dogma is challenged. This is a good thing. But what would be unfortunate is if this paper is hyped as a cure for female infertility. A lot more work is needed to understand what these new cells really are, and to verify the findings and the claims.
“This is another chapter in what has been a very controversial story, where some scientists have gone against the dogma which states that in mammals, such as mice and humans, all the progenitor germ cells that could give rise to eggs have already done so by birth.”
Other experts said the work was interesting, but needed to be replicated before its implications were clear. Professor Azim Surani, of the University of Cambridge, said: “Sperm are produced continuously in men, but the number of eggs in women is fixed at birth.
“This new study in mice now suggests that there are also stem cells present in ovaries that can be cultured in a dish, which upon transfer to ovaries can develop into viable eggs and give rise to offspring. This finding, if confirmed independently, could advance understanding of these ovarian stem cells and advance research on female infertility.”
In the study, which is published in the journal Nature Cell Biology, the Shanghai group, led by Kang Zou and Ji Wu, isolated cells they call female germline stem cells (FGSCs) from the ovaries of five-day-old and adult mice. They then grew these cells into a colony that kept dividing in culture. The scientists then killed off all the eggs in the ovaries of adult mice, and reseeded them with FGSCs that had been genetically modified to produce a green fluorescent protein.
The sterilised mice produced new eggs, which when fertilised gave rise to healthy babies that were themselves fertile. The green fluorescent protein was present in many of the babies, which suggests they came from eggs grown from the stem cells.
“These findings contribute to basic research into oogenesis [egg production] and stem cell self-renewal, and open up new possibilities for use of FGSCs in biotechnology and medicine,” the scientists said.
Professor Lovell-Badge, however, said the Chinese paper did not prove that the eggs that gave rise to babies came from the stem cells. When the mice were sterilised, not all of their eggs were killed, and these could have produced the young. The virus that was used to modify the stem cells with the green fluorescent protein could also have infected some of these remaining eggs, which would account for the protein’s presence in some of the offspring. “Extraordinary claims require extraordinary evidence, whereas to me this is a very incomplete piece of work that will only add to the confusion,” he said.
“If true, and especially if applicable also to humans, then this is very important. For example, it could provide a means to restore fertility to women who have few eggs or who have had to undergo cancer treatments, by isolating these cells, expanding their number in culture and keeping them frozen until needed for IVF.”
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