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Mature sperm and eggs grown from same stem cells

June 23, 2006 By Jo Marchant This article courtesy of Nature News.

Technological advance could help infertile people to have children.

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Stem cells from a mouse embryo have been coaxed into producing both eggs and sperm in the same dish. The eggs and sperm are the most mature yet grown in the lab, and the advance brings researchers closer to their ultimate aim: producing human eggs and sperm from adult body cells so that infertile men and women can have their own children.

Applying the technique to humans would be controversial, not least because it raises the possibility that men might be able to produce eggs, and women sperm. But researchers point out that any human application would be decades away, which would allow time for ethical debate over the technology.

In the meantime, they hope that lab-produced eggs and sperm will help them to learn exactly how these cells are created in the body, something that is crucial to understanding fertility disorders and embryo development.

The achievement builds on previous work using mouse embryonic stem cells to grow eggs and sperm. In 2003, Hans Schöler of the University of Pennsylvania in Philadelphia and his colleagues reported that after such cells had been cultured for around 40 days, some of them spontaneously produced eggs1.

Everyone's looking to see if we'll be able to get some more eggs from somewhere.
Irina Kerkis
Roger Abdelmassih Clinic, Sao Paolo
The following year, researchers led by George Daley of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, coaxed cells into producing sperm precursors, by adding a chemical messenger called retinoic acid2. These cells did not form mature sperm, but were able to fertilize eggs when injected into them.

Irina Kerkis from the Roger Abdelmassih Clinic in Sao Paolo, Brazil, and her colleagues hoped to find a more efficient way to grow eggs. So they decided to see whether retinoic acid could trigger egg as well as sperm production.

They took cells cultured from a male mouse embryo and grew them into hollow balls called embryoid bodies, which look rather like early embryos. Then they grew them with retinoic acid for four days.

Two weeks later they were surprised to see both eggs and sperm produced. Cells on the outside of the embryoid bodies turned into mature, elongated sperm, whereas cells on the inside formed follicles, which released eggs. The eggs developed into embryo-like structures called blastocysts that then 'hatched', a process that normally occurs just before an embryo implants into the uterus wall.

Further than ever before

Kerkis says the embryos probably formed by a process known as parthenogenesis, in which an unfertilized egg can develop into an embryo-like structure. In mammals, such 'parthenotes' never develop past implantation. But because mature sperm were present in the same dish, Kerkis claims it's possible they could have fertilized the eggs. Although she admits it is unlikely, she is currently carrying out tests to investigate whether it occurred.

Kerkis presented her results at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Prague on 21 June. She says the eggs were produced more quickly and efficiently than in previous work, and that the resulting embryo-like structures developed further than has been seen before.

Alan Trounson, a stem-cell researcher at Monash University in Melbourne, Australia, is impressed by the eggs and sperm produced. "I haven't seen sperm of that maturity produced in the lab," he says.

He cautions that the work is at an early stage, and points out that for such work to be of therapeutic use in humans, researchers will require much better control over the process. "It will need to be much more directed," he says.

Future fertility

The idea is that eventually, infertile men or women could clone a body cell to produce an embryo, from which embryonic stem cells would then be extracted. These could then be coaxed into producing viable eggs or sperm. That would be "a big loop", admits Trounson, but he says it could be possible within 20 or 30 years.

In the meantime, eggs produced in the lab would be of use for research, for example to produce embryonic stem-cell lines. Harvesting eggs from women is a painful and risky process, so the supply of eggs is a major limiting factor. "Everyone's looking to see if we'll be able to get some more eggs from somewhere," says Kerkis.

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References

  1. Habner K., et al. Science, 300. 1251 - 1256 (2003).
  2. Geijsen N., et al. Nature, 427. 148 - 154 (2004).

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