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MEN ARE YOU THINKING OF DELAYING FATHERHOOD? READ THIS BEFORE YOU DO

Men delaying fatherhood 'should understand the risks'.
As a man ages,
his Sperm contains an increasing proportion of cells with selfish mutations, say the researchers.
For the first time, scientists have pinpointed the source of some severe disease-causing mutations in sperm-producing tubes inside the testicles of healthy men.

Andrew Wilkie, Nuffield professor of pathology at the University of Oxford in the UK, and colleagues describe their findings in a paper published in the Proceedings of the National Academy of Sciences.
The authors suggest their work should help us better understand how genetic diseases can arise in children born to parents who do not themselves have them.

Men are not born with ready-made sperm cells unlike women that are born with all their egg cells. Sperm production starts in puberty, in a tangle of spaghetti-like tubes - the seminiferous tubules - inside the testicles. Each testicle contains about 400 m of seminiferous tubules.

Inside the seminiferous tubules, special stem cells called spermatogonia generate sperm cells. A spermatogonium divides into two cells - one that eventually matures into a sperm cell, and the other is a new spermatogonium so the cycle can repeat itself. A man's testicles produce millions of sperm and new spermatogonia every day in this way.

At each cell cycle, the DNA in the old spermatogonium is copied into the two new cells - the new spermatogonium and the cell destined to be a sperm cell. But every so often, a copy error - a mutation - arises in the DNA, which carries on in new generations of cells. The Proportion of sperm with 'selfish mutations' increases with age.

Some DNA mutations are harmless while some are not and can give rise to genetic disorders. But the researchers found out that in some cases, the proportion of sperm cells carrying a particular mutation is much higher than one might expect from spontaneous copying errors in spermatogonia.

They showed that some mutations that occur in the spermatogonia enhance their own chances of propagating forward - they call them "selfish mutations."It appears that the effect of selfish mutations is to cause spermatogonia to give rise to more than one new spermatogonium at each cell cycle, each carrying the mutation.

Thus, as a man ages, and his sperm production undergoes more cell cycles, his sperm contains an increasing proportion of cells with selfish mutations.
The researchers liken the process to cancer, where defective cells grow at a faster rate than healthy cells and eventually form a tumor.

In their study, they investigated a rare genetic disease called Apert Syndrome that affects the development of the skull and limbs. The disease affects about 1 in 60,000-70,000 babies.

Older men tend to produce more Apert mutations
The parents of most children born with Apert syndrome do not have it, and Prof. Wilkie and colleagues - who have been studying it for 20 years - have shown that it is caused by new mutations in a gene called FGFR2 that arise spontaneously in the father's sperm production.

Based on the knowledge of how spontaneous mutations happen, one might expect Apert syndrome to be extremely rare, and indeed it is - but, note the authors, cases occur up to 1,000 times more frequently than they ought to on this basis.

To find out why Apert syndrome is more common than expected, the team compared sperm from fathers of children with and without the disease and found that both groups had rare sperm cells with the FGFR2 mutation.

"The process that gives rise to Apert syndrome happens in every man, meaning any couple could have a child with Apert syndrome, regardless of the health of the parents." ; according to Coauthor Anne Goriely, associate professor of human genetics at Oxford.
However, she says they found that older men tended to produce more of the Apert mutations.

The team found that normal men also produce sperm with other mutations that cause lethal forms of dwarfism and other severe diseases. But because there are so many millions of sperm, the chances of a mutation being in a sperm that fertilizes an egg are very low.

In their study, the team identified where the mutant cells grow inside the testicles of normal men. They examined the seminiferous tubules of men whose testicles had been removed for surgical reasons and who had donated them for research.

They developed techniques to pinpoint the abnormal regions of the seminiferous tubules, and using a laser-powered microscope, they could isolate the regions and perform detailed genetic analyses. From these analyses they identified mutations linked to severe diseases in 13 of the 14 donated testicles.
The researchers note that all men will develop these mutant growths in their testicles as they age. However, as men are tending to delay fatherhood, it is important to understand the risks, they suggest.

Meanwhile, Medical News Today recently learned of a study that found a man's weight affects the genetic information contained in his sperm. The researchers suggest a child's predisposition to obesity may be inherited via epigenetic marks on the DNA of the father's sperm.



This post first appeared on Welcome To Life And Fertility, please read the originial post: here

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MEN ARE YOU THINKING OF DELAYING FATHERHOOD? READ THIS BEFORE YOU DO

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