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No new eggs from bone marrow cells

16 June 2006
Appeared in BioNews 363

A new US study has cast serious doubt on controversial research that suggested bone marrow stem cells can produce new eggs in adult mice. Last year, a team based at Massachusetts General Hospital reported in the journal Cell that the eggs of mice rendered sterile could regenerate within 24 hours, following bone marrow transplants. However, in a new paper published online by Nature, scientists based at Harvard University and the Joslin Diabetes Center say they have found no evidence to back up the claims.

The Massachusetts researchers found that when they destroyed egg-containing follicles with the drug doxorubicin, hundreds of new eggs appeared within 24 hours. The scientists also transplanted bone marrow from healthy mice into mice sterilised with two chemotherapy drugs, cyclophosphamide and busulfan. They found that new egg cells appeared in the ovaries of the treated mice one to seven days after transplantation, with egg cells still present 11 months later. The researchers got similar results when they transplanted bone marrow from normal mice into animals incapable of producing mature germ cells.

The results caused a sensation when they were published, since they appeared to contradict the long-held belief that female mammals are born with a lifetime's supply of eggs. Instead, they provided evidence for the existence of 'ovary stem cells' that continue to make new eggs throughout the animal's life. At the time, team leader Jonathon Tilly said: 'Everyone had missed finding female germline stem cells because they are not in the ovaries, where everyone would have looked for them', Now, it seems that such stem cells may not actually exist - at least not in bone marrow.

In the latest study, the researchers wanted to find out if the new eggs reported in Tilly's study could be ovulated (released from the ovary), and whether or not ovary regeneration by bone marrow cells was a normal process. The team used 'parabiotic' mice - pairs of animals that have the skin between their front and hind legs sewn together, so they share a blood circulatory system. One mouse in each pair was normal, while the other had been genetically altered to produce green fluorescent protein (GFP) in all its tissues. Eve after eight months of sharing their blood, the normal mice produced no eggs tagged with GFP, and the GFP mice produced no normal eggs. This, say the scientists, is proof that circulating bone marrow stem cells do not normally produce new eggs.

The team carried out another experiment, in which one mouse in each pair had received chemotherapy drugs to destroy its own eggs. But again, the researchers found no evidence of the damaged ovaries being replenished with cells from the other mouse. 'This is a pretty powerful denial of the idea that new eggs form and contribute to fertility', said co-author Roger Gosden, of Cornell University in New York. Other scientists agree: 'It incontestably shows that the Tilly work is simply not true', David Albertini of Kansas University told Nature.

But Tilly says the new research does not contradict his own findings, since he looked at immature eggs still in the ovary, whereas the latest study focussed on ovulated eggs. He says that replenished, immature egg cells could still be crucial to fertility, even if they are never released by the ovary. Gosden concedes that dormant egg stem cells, which can be 'brought back to life' in the lab, could still exist. 'I think the Tilly group might be right to some extent on that one', he said.

Bone Marrow Fails to Produce Oocytes
Science |  16 June 2006
Born or made? Debate on mouse eggs reignites
Nature |  15 June 2006
Joslin study refutes recent report that bone marrow can replenish female oocytes
EurekaAlert |  14 June 2006
12 March 2012 - by Professor Robin Lovell-Badge 
I am all for challenging dogma, but to do so requires robust evidence and carefully drawn conclusions. In the case of Professor Jonathan Tilly's much-trumpeted study on stem cells in ovaries that can give rise to eggs, I feel that both were missing...
27 February 2012 - by Antony Starza-Allen 
Scientists in the USA have shown it may be possible to isolate egg-producing stem cells from women's ovaries....
20 April 2009 - by Dr Charlotte Maden 
New work in stem cell research has challenged the long-standing belief that women are born with all the eggs they will ever need. The results were published in the journal Nature Stem Cell, although the study was received with caution. The scientists at Shanghai Jiao Tong University...
21 May 2007 - by Stuart Scott 
Hopes aroused by a controversial study suggesting that women may be able to produce new egg cells have been seemingly dashed. The 2005 paper, published in the journal Cell by researchers at Massachusetts General Hospital, fleetingly gave hope to infertile women when it suggested that egg production...
1 August 2005 - by BioNews 
Bone marrow stem cells can produce new eggs in adult mice, US researchers say. A team based at Massachusetts General Hospital has shown that the eggs of mice rendered sterile with a drug can regenerate within 24 hours, and that these germ cells originate from bone marrow. The findings, published...
8 May 2005 - by BioNews 
US researchers have managed to grow human eggs in the laboratory, using cells scraped from the surface of ovaries. The team, based at the University of Tennessee, Knoxville, say that the findings could lead to a new way of preserving female fertility, and also a potential new source of egg...
5 July 2004 - by BioNews 
The ovaries of adult mice contain egg-generating germ cells, scientists revealed at the European Society for Human Reproduction and Embryology's annual conference. The results have prompted hopes of a treatment for women with few eggs, such as those treated for cancer or nearing menopause. The discovery had been published in...
15 March 2004 - by BioNews 
Mammals may continue to produce new eggs throughout their lives, a study carried out on mice suggests. The findings challenge the long-held belief that female humans, mice and other mammals are born with a finite supply of eggs, which lasts until the menopause. A team of researchers at the Massachusetts...
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