Tuesday, August 01, 2006

Stem Cells Can Become Normal Sperm

Researchers are very close to creating sperm outside of the body for the first time, New Scientist has learned.

As reported on 1 May, the feat has already been achieved with eggs. It was accomplished with cells originally derived from mouse embryos, but most experts see no reason why the technique would not work with human embryonic stem cells too. If human eggs and sperm created this way are healthy - and it is a big if - the implications for reproductive technology and regenerative medicine would be immense.

Intriguingly, eggs form from both female (XX) and male (XY) ESCs. That is because mammalian germ cells will go down the egg route unless signals produced by the testes tell the cells to become sperm.

This is also why getting ESCs to turn into sperm is more complex. However, a team led by Toshiaki Noce at the Mitsubishi Kagaku Institute of Life Sciences in Tokyo may already have succeeded. According to a document found by New Scientist, the team allowed male mouse ESCs to develop spontaneously into various different types of cell, and picked out those that had begun turning into germ cells.
'Normal sperm'

These cells do not develop far in culture, but when Noce's team transplanted them into testicular tissue he found after three months that they had undergone meiosis and formed what appeared to be normal sperm.

The critical next step would be to fertilise the artificial eggs with normal sperm, or use the artificial sperm to fertilise normal eggs.

The big question is whether the resulting embryos will have normal imprinting and develop into healthy baby mice. "There is always a possibility that the imprints would not be normal," says Azim Surani of Cambridge University.

If the animals are normal, the race will be on to create artificial human egg and sperm cells this way. It is likely to be much harder with human cells. Attempts to obtain human eggs simply by growing slices of ovarian tissue have failed, and the only mouse created from an egg obtained this way, dubbed Eggbert, was sickly and died young. It will also be slow: it takes up to six months for a human egg to mature.
Two men

But if it can be done, the possibilities are astounding. In cloning, for instance, there are massive problems with imprinting. When a nucleus is transferred to an empty egg, chemicals in the egg seem to alter the imprinting, "reprogramming" the genome to ensure the right genes are expressed in the growing embryo. But the process is far from perfect, and many cloned embryos die or give rise to animals with major defects.

The offspring of cloned animals, however, seem to be normal, prompting some cloning experts to suggest that the formation of eggs and sperm corrects any lingering imprinting defects. It might be possible to take an individual's cell, create ESCs from it by therapeutic cloning, and then derive healthy eggs or sperm from them for use in IVF.

The most obvious application would be to treat infertile women who cannot produce any eggs suitable for IVF, or men who cannot produce sperm. And because male ESCs can be turned into eggs as well as sperm, two men could both be biological parents of a child, with the help of a surrogate mother; two out of three of such children would be male.
Potential risks

The technique would not allow two women to have children together, though, as female ECSs lack the Y chromosome, without which sperm cells appear unable to form.

For now, the potential risks of the technology rule out such uses. Yet while some countries have regulations that would prohibit the use of the technology, in the US and other countries there is far less control of IVF clinics.

Now may be the time to consider the potential benefits and concerns, before experiments even begin with human cells. "It's always good to have these kinds of debates of potential ethical issues," says Surani.

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