Mutant sperm-factories spread in testes

Mutant sperm-factories spread in men's testicles as they age to increase the risk of children with genetic diseases, researchers have shown.

Millions of spermatogonia produce a constant supply of sperm in the testes.

But the University of Oxford study showed mutant spermatogonia gain a "tumour-like" competitive edge, leading to a greater proportion of sperm becoming defective.

Experts said couples should consider having children earlier in life.

A range of diseases including autism and schizophrenia are more likely with older dads due to mutations in their sperm.

And the risk of very serious health problems goes from around four in every 200 births to five in every 200 once the father passes the age of 50.

Mature sperm

The study, published in Proceedings of the National Academy of Sciences, analysed 14 testes from men aged between 39 and 90.

The sexual organs were considered healthy, but were removed for other conditions such as a hernia causing swelling in the groin.

The researchers explored the "massive tangle of spaghetti" inside the testes to find the areas producing diseased sperm.

The analysis of the DNA - the instructions for life - in those defective zones showed mutations linked to a range of bodily processes.

They were linked to malformations and a predisposition to cancer, but they also had a role in growth and reproduction in the testes.

The same mutations that were ultimately damaging to children were encouraging the defective spermatogonia to spread - leading to a greater proportion of sperm being defective.

Prof Andrew Wilkie, one of the researchers, told the BBC: "This is why we call it selfish selection.

"These mutations within the testes get an advantage over their normal neighbours, but if that sperm fertilises an egg then that [mutation] carries a disadvantage to that person and causes disease.

"It's the first time anyone has been able to look at a piece of testis and say that's where this is happening."

That "selfish" growth is more commonly seen in cancer.

The researchers were able to find the mutations because their impact is so severe.

It is still unclear what the study means for the sections of DNA that increase the risk of disorders such as autism.

Allan Pacey, a professor of andrology at the University of Sheffield, said the risks associated with being an older dad were well known.

But he told the BBC the explanation had been unclear: "These are important processes to understand because more and more men are waiting until they are older before they have their children.

"Moreover, it is a sobering reminder that men are not as immune from reproductive ageing as we might think.

"If they have a choice, couples should always consider having their children earlier in their lives than perhaps they want to."

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