Behind the Headlines

Tuesday April 14 2009

Further research is needed to confirm the results of this study.

Stem cell treatment may “allow women to delay menopause” and “replenish the supply of fresh eggs in infertile women” according to The Independent.
These claims come from a study in mice that transplanted stem cells from immature and mature ovaries into infertile female mice. Following the transplant, the mice could produce healthy offspring after mating.

As the researchers suggest, this technique is likely to be useful for studying the biology behind egg cell development. However, further research is needed to confirm the study’s findings and to determine whether humans also have this type of cell in their ovaries after birth. Until then, it is not possible to say whether a similar technique could be used to treat human female infertility.

It is certainly too early to suggest that an infertility ‘cure’ for women is on the way on the basis of this research.

Where did the story come from?

Dr Kang Zou and colleagues from Shanghai Jiao Tong University, China carried out this research. The study was sponsored by the Shanghai Pujiang Program and Shanghai Leading Academic Discipline Project, and supported by the Key Program of National Natural Scientific Foundation of China. The study       was published in the peer-reviewed scientific journal, Nature Cell Biology.

What kind of scientific study was this?

This was an animal study in mice, looking at whether stem cells in a newborn mouse’s ovaries could be used in sterilised mice to generate fully functional eggs and subsequent healthy offspring.

Previously it had been thought that the ovaries of most female mammals produce a lifetime’s supply of eggs before they are born, and that after birth no new egg cells can be produced.

In contrast, recent research has suggested that the ovaries of young and adult mice do contain cells that can divide. However, it is unclear whether these cells come from the ovary rather than from the blood stream from the bone marrow, and whether these dividing cells have the ability to produce eggs that can be fertilised and produce healthy offspring.

The researchers took the ovaries of adult and five-day-old mice and looked to see if they contained cells that were producing a protein called MVH. This protein is found only in the type of cells that will produce egg cells, called germline cells. They then looked at whether these cells were dividing, by ‘labelling’ them with a fluorescent marker chemical that is only taken up by the cell if it is dividing.

Once they had established that these germline cells were present, the researchers used special techniques to isolate them from the ovaries of adult and five-day-old mice. They then checked to see whether these cells were dividing and could be grown in the laboratory. The researchers then examined the cells grown in the laboratory to see if they looked like typical embryonic stem cells.

The researchers also looked at how long the cells could be grown in the laboratory, whether they could survive being frozen and thawed, which genes were switched on in these cells and whether the chromosomes appeared normal under the microscope.

In the second phase of their experiments, the researchers sterilised adult female mice using drugs that destroyed their egg cells. They then transplanted some of their laboratory grown germline cells that had been ‘tagged’ with a green fluorescent protein (GFP) into the ovaries of these mice. Two months after the transplant, they removed the ovaries and examined them for cells that looked like egg cells (oocytes) and that contained GFP. They compared these with the ovaries of sterilised mice that had not received the transplant (controls).

The researchers repeated these transplant experiments with 20 more female mice, and mated them with normal male mice to see whether the developing egg cells could be fertilised and produce healthy offspring. They included seven unsterilised controls for this experiment.

What were the results of the study?

The researchers identified cells from the ovaries of both adult and five-day-old mice that had the characteristics of egg-producing germline cells, in that they produced a protein typical of this type of cells and were dividing.

The researchers found that they could extract these germline cells from the mouse ovaries and grow them in the laboratory, where they would continue to divide. The cells from adult mouse ovaries were successfully grown in the laboratory for six months and those from newborn mice for 15 months by the time the researchers wrote their research paper. The cells could be frozen and thawed, and still grown in the laboratory afterward.

The cells had switched-on genes that were typical of germline cells and also showed some characteristics of stem cells, suggesting that they were female germline stem cells (FGSCs). The chromosomes in these cells appeared normal.

When the FGSCs were transplanted into the ovaries of sterilised adult female mice, these cells developed into cells that looked like egg cells in various stages of development. No egg cells had developed in the ovaries of control mice.

When sterilised mice that received an FGSC transplant were mated, about 80% produced healthy offspring that were themselves fertile. Some of these mice still had the green fluorescent protein ‘tag’ that had been inserted into the FGSCs  when they were grown in the laboratory, which suggested that they came from eggs grown from the transplanted cells.

What interpretations did the researchers draw from these results?

The researchers conclude that their findings contribute to basic research about the formation of egg cells. They also suggest that they “open up new possibilities for use of [female germline stem cells] in biotechnology and medicine”.

What does the NHS Knowledge Service make of this study?

This study has shown that the ovaries of newborn and adult mice do contain cells that can develop into egg cells if transplanted into the ovaries of sterilised mice. As the researchers suggest, their technique is likely to be a useful tool in the studying the biology of egg cell development.

It should be noted that the second experiment that produced live offspring from sterilised mice did not include any control sterilised mice that did not received a transplant, which could show that they did not recover fertility naturally. Although the fact that some of the offspring mice carried the green fluorescent protein tag suggested that they did come from the transplanted germ cells, other researchers, including Professor Robin Lovell-Badge of the MRC National Institute for Medical Research in London, have suggested that the virus used for this tagging could also have infected any remaining eggs in these mice. This would account for this protein’s presence in some of the offspring.

Ideally, this research will need to be independently repeated using similarly sterilised mice as controls for the mating experiments. Further research will also be needed to determine whether other mammals, including humans, have this type of cell in their ovaries after birth.

Until the results of this further research are known, it is not possible to say whether a similar technique might be used to treat female infertility in humans.

Links to the headlines

Stem cell treatment may allow women to delay menopause. The Independent, April 14 2009

Stem cell study may raise prospect of new fertility treatment, say scientists. The Guardian, April 14 2009

‘Cure’ on way for infertile women. The Sun, April 14 2009

Stem cell discovery raises hopes of restoring female fertility. The Times, April 14 2009

Links to the science

Zou K, Yuan Z, Yang Z et al. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nature Cell Biolog. [Advanced online publication] April 12 2009

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Edited by NHS Choices