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Obese men found to make sperm with thousands of modified genes

By Andy Coghlan

3 December 2015

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Now there’s even more reason to watch your waistline. A man’s weight seems to influence gene activity in his sperm, which might be passed on to any children he has.

“Our results suggest that environmentally driven changes carried in sperm cells could represent a mechanism by which obesity is transmitted to the next generation,” says of the University of Copenhagen in Denmark. He suggests his findings might lead parents-to-be to consider changing their behaviour before conceiving.

We already know that a child’s weight seems to be highly linked to that of their parents. So far, much research into how obesity is passed on has focused on mothers and their diet before or during pregnancy. But the new study suggests that the father’s health may also be important.

Comparing the sperm of 13 lean and 10 moderately obese men, Barr猫s and his team have found striking differences in their epigenomes 鈥 the marks on DNA that affect how active different genes are. “We found around 9000 genes epigenetically changed in obese men,” says Barr猫s.

This includes the FTO gene, the only gene so far that has been unequivocally linked to obesity. Overall, the team identified epigenetic changes affecting 300 genes that have been linked to behaviour, including eating patterns and habits, Barr猫s says.

Sins of the father

“The results add to the body of evidence that we are not just products of ‘what our mothers ate’, but also ‘what our fathers ate’,” says at the University of Cambridge.

It was thought that epigenetic changes couldn’t be passed across human generations because patterns of DNA methylation 鈥 a type of epigenetic change that makes a gene less active 鈥 are wiped clean soon after fertilisation.

However, research earlier this year found that some genes seem to escape this cleansing. And there’s evidence that short fragments of RNA that dictate which genes are methylated can be passed on via sperm. Barr猫s’s study found a higher level of these kinds of short RNA strands in obese men’s sperm, including one that is known to target CART, a gene that controls appetite.

“We’ve not studied the transmission of these epigenetic marks to the offspring, but we are currently doing this,” says Barr猫s. “We hypothesise that several epigenetic marks act in concert, after fertilisation, to change the developmental programming of the embryo.”

But epigenetic changes like these aren’t necessarily permanent. When Barr猫s’s team analysed the sperm epigenomes of six massively obese men who underwent bariatric surgery to help them lose weight, they found that after only a week, the methylation of 1500 genes had been changed. A year later, some 4000 genes had been altered.

But of these, only 2700 genes had been identified in the earlier experiment, and the majority of these did not now match the pattern seen in the lean group of men.

“It could just be that surgery induces different epigenetic patterns that somewhat compensate for the obesity-associated ones,” says of the University of Zurich.

However, without controls, we can’t know for sure that some of these changes weren’t simply the result of time passing, says Barr猫s.

Journal reference: Cell Metabolism, DOI: 10.1016/j.cmet.2015.11.004

(Image credit: Ian Hooton/Science Photo Library/Corbis)

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