Fw: Water? Common virus linked to male infertility /Germline gene therapy boosted by modified sperm

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Steven.Powers.MD

Sunday, October 28, 2001 2:46 AM

Common virus linked to male infertility /Germline gene therapy

boosted by modified sperm

 

 

Don't expect the drinking water helps with all the estrogen in.

N Common virus linked to male infertility

http://www.newscientist.com/news/news.jsp?id=ns99991483

13:20 26 October 01

Emma Young

 

A common virus may be linked to infertility in men, say German scientists.

They analysed semen samples from almost 100 men and found that 38 per cent

of abnormal samples were infected with adeno-associated virus (AAV),

compared with only 4.6 per cent of normal samples.

 

AAV infects 40 per cent of people by the age of 20 and most people are

infected by middle age.

 

" The virus was not thought to be pathogenic, " says Jörg Schlehofer of the

German Cancer Research Centre in Heidelberg, who led the new research. " But

our research raises the issue of whether sperm cells used in ICSI or other

reproductive techniques should be checked for AAV prior to fertilisation. "

ICSI involves injecting a single sperm directly into an egg.

 

Christopher Barratt, an expert on sperm biology at Birmingham University,

says: " The idea that infection with certain viruses - such as HIV - can

cause sperm abnormalities is not new. But AAV is not generally thought to be

pathogenic and that's what makes this finding interesting. "

 

AAV is used in gene therapy, to shuttle new DNA into a cell. It has recently

been used to introduce DNA into mice sperm stem cells. " The virus is a very

good vector system. But nobody has really looked at what tissues it targets

in humans, " says Schlehofer. More work is needed to investigate whether AAV

infection really does cause infertility, he says.

 

 

Strong bond

 

 

Schlehofer's team analysed semen samples from 73 men who were participating

in a fertility programme and 22 men with no history of infertility.

 

They used standard DNA analysis techniques to look for traces of the virus.

Earlier work by the team on a small number of infertile men had found

evidence of a high AAV infection rate. This work also showed that the viral

DNA bound strongly with the sperm, but not with other constituents of semen.

" But these were very few men, and we did not look at normal samples, " says

Schlehofer.

 

In the new study, they found that men with either very low sperm

concentrations or defects in sperm motility were most likely to be infected

with AAV.

 

There is some evidence that the virus can interfere with cell

differentiation. " It could be that important cells associated with the

production of sperm and sperm maturation could be affected, and this results

in the malformations, " says Schlehofer.

 

 

Early miscarriage

 

 

AAV infection has previously been linked to very early miscarriage.

 

" It is possible that if an embryo is infected through an infected sperm, for

example, the very sophisticated immunotolerance between the embryo and the

mother is affected, and this could trigger miscarriage. But this is

speculation - much more work needs to be done to investigate, " says

Schlehofer.

 

There is no " cure " for AAV, since it was not thought to be harmful to

health, he adds. " But with ICSI, for example, there is not a very high baby

take-home rate. Maybe this is due to infected sperm. If we could screen

samples or get rid of the virus in assisted reproduction techniques, perhaps

we could improve this rate, " Schlehofer says.

 

It is not clear how AAV infection of the testis could occur, the team says.

But it appears that the virus does " target " genital tissue in particular.

 

Journal reference: Human Reproduction (vol 16, p 2333)

 

Germline gene therapy boosted by modified sperm

http://www.newscientist.com/news/news.jsp?id=ns99991462

13:18 23 October 01

Emma Young

 

Using genetically modified sperm to prevent disease in future generations

has come a step closer, say US scientists. They have succeeded in using a

virus to introduce a foreign gene into up to 20 per cent of mouse sperm stem

cells. This gene was then passed on for at least three generations.

 

Gene therapy to treat genetic disease in adults has shown some success. But

previous attempts to modify sperm for 'germline' therapy - in which

modifications are passed to offspring - have not produced good results, say

Ralph Brinster of the University of Pennsylvania and his colleagues.

 

Culturing samples of stem cells for a shorter period of time allowed them to

introduce a marker gene into 20 per cent of mouse sperm stem cells. This

represents a ten-fold increase in success rate over past attempts.

 

These cells were then transplanted into recipient mice. The inserted foreign

genes appeared in about 4.5 per cent of the offspring of these mice

 

 

Self-renewing

 

 

" Spermatatogonial " stem cells, which are found in the testes throughout

life, are the only cells in the male that self-renew after birth and

contribute genes to subsequent generations. " These cells are thought by some

to provide the best approach, should human germline therapy be undertaken in

the future, " Brinster says.

 

The number of stem cells in cultured testis samples is known to decrease by

about half after three days and by 90 per cent after seven days, the team

say. They suggest that a shorter culture time could be a key reason for

their improved results.

 

The idea of germline engineering in humans is controversial. Some argue it

could lead to unforeseen side effects being passed down generations of

people. The technique is more likely to be applied to livestock in the short

term.

 

It could enable the production of herds or flocks of animals modified to be

more disease-resistant, to produce useful proteins in their milk or to act

as better models for human diseases.

 

Journal reference: Proceedings of the National Academy of Sciences (vol 2,

no 43)