WOMEN have long been told that they are born with a fixed number of eggs that eventually run out, triggering the menopause. But now it seems that there may be a way for a woman to replenish her egg stocks.
More surprising still is where this egg recharge comes from – stem cells lodged in the bone marrow. If the researchers can show that these bone marrow-derived eggs can be fertilised and produce healthy offspring, the implications for fertility treatment are huge.
“Women could extend their fertility by harvesting stem cells from their blood and storing them for later use”
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“This flies in the face of current dogma about a restricted population of [ovarian] follicles existing in the adult,” says Lyle Armstrong at the University of Newcastle upon Tyne, UK, who was not involved in the work but has been trying to generate human eggs, or oocytes, from embryonic stem cells. The discovery means that women could extend their fertility by harvesting stem cells from their blood and storing them for later use. “But potentially more exciting is that we may be able to generate oocytes in massive numbers,” says Jonathan Tilly at Massachusetts General Hospital in Boston, who led the team that made the discovery. This would have enormous implications in terms of therapeutic cloning, he adds.
Tilly and his colleagues located germ cells – the precursors to egg and sperm cells – in blood and bone marrow from mice by identifying the expression of characteristic genes. Remarkably, when these cells were transplanted into female mice that had been sterilised by drugs used in human chemotherapy, the mice developed new egg cells along with supporting follicles in their ovaries. After two months their ovaries were indistinguishable from those of normal fertile mice (Cell, vol 122, p 303).
The findings would help explain the medical mystery of why hundreds of women who have been sterilised by chemotherapy suddenly begin menstruating after having bone marrow transplants and blood transfusions. Some even conceive. If borne out, the study would raise fresh questions about the maternity of such children: if the ovaries of these women had been refreshed by stem cells from a donor, the offspring would genetically belong to the donor.
Not everyone is convinced. “What they have done is potentially important, but they should have taken it further to see whether these cells could form oocytes that can be fertilised,” says developmental geneticist Robin Lovell-Badge at the National Institute for Medical Research in London. “That is the proof that you have a germ cell.” According to Tilly, such experiments are under way. If proved right, “that would be the final nail in the coffin of the story that females are born with a fixed number of eggs”, he says.
He now believes that the ovary is part of a three-tiered system in which germ-line stem cells in the bone marrow manufacture immature germ cells that travel through the bloodstream to the ovary, where they implant themselves and mature into eggs.
If this is true, there must be molecular messengers that carry information between ovary and bone marrow. Identifying these messengers could make new fertility treatments possible. They could be used to stimulate egg production by the bone marrow, for example.
