Scientists are investigating the epigenetics of fatherhood: how a man’s experiences can alter his sperm, and whether those changes in turn may alter his children. Credit Dann Tardif/LWA, via Corbis
A week before the operation, the man provided a sperm sample to Danish scientists. A week after the procedure, he did so again. A year later, he donated a third sample.
Scientists were investigating a tantalizing but controversial hypothesis: that a man’s experiences can alter his sperm, and that those changes in turn may alter his children.
That idea runs counter to standard thinking about heredity: that parents pass down only genes to their children. People inherit genes that predispose them to obesity, or stress, or cancer — or they don’t. Whether one’s parents actually were obese or continually anxious doesn’t rewrite those genes.
Yet a number of animal experiments in recent years have challenged conventional thinking on heredity, suggesting that something more is at work.
In 2010, for example, Dr. Romain Barres of the University of Copenhagen and his colleagues fed male rats a high-fat diet and then mated them with females. Compared with male rats fed a regular diet, those on the high-fat diet fathered offspring that tended to gain more weight, develop more fat and have more trouble regulating insulin levels.
Eating high-fat food is just one of several experiences a father can have that can change his offspring. Stress is another. Male rats exposed to stressful experiences — like smelling the odor of a fox — will father pups that have a dampened response to stress.
To find the link between a father’s experiences and his offspring’s biology, scientists have taken a close look at sperm. A sperm cell delivers DNA to an egg, of course. But those genes are regulated by swarms of molecules, so-called epigenetic factors.
These molecules can respond to environmental influences by silencing some genes and activating others as needed. Some studies suggest the changes in epigenetic factors can be handed down to offspring via sperm.
When Dr. Tracy L. Bale, a neuroscientist at the University of Pennsylvania, and her colleagues looked at the sperm of stressed male rats, for example, they found unusual levels of epigenetic molecules called microRNAs.
They created a cocktail of microRNAs and injected them into embryos from mellow fathers. As Dr. Bale and her colleagues reported recently, the embryos developed into rats with altered stress responses.
The notion that environmental responses might influence human health in similar ways has huge implications. But scientists have only started to investigate the epigenetics of fatherhood. As is often the case when scientists turn from animal experiments to humans, the results have been provocative but hardly clear-cut.
In 2013, Adelheid Soubry, a molecular epidemiologist at KU Leuven University in Belgium, and her colleagues studied 79 newborn children. They found epigenetic differences between children with obese fathers and those with lean ones.
Are changes like these actually caused by men’s obesity? Dr. Barres and his colleagues set out to investigate that potential link in two ways.
First, they collected sperm from 10 obese Danish men and 13 lean ones. They found numerous epigenetic differences. One type of epigenetic factor they looked at involved molecular caps that are placed on DNA in a process called methylation. Dr. Barres and his colleagues found more than 9,000 genes in which the methylation pattern differed between lean and obese men.
Then the scientists recruited six obese men getting bariatric surgery to see how losing weight changed these methylation patterns. In a report published on Thursday in the journal Cell Metabolism, Dr. Barres and his colleagues identified more than 3,900 genes that were methylated differently a year after surgery.
Among the genes that are epigenetically altered are those that affect such behaviors as appetite control. But the new study does not show whether those changes have any effect on a father’s children, Dr. Barres said.
“I don’t want to speculate whether it’s positive or negative in the following generation,” he said.
Dr. Barres and his colleagues are now expanding on the study by comparing epigenetic patterns in the sperm of obese fathers with the patterns in the blood cells of their offspring. “We’re going to try to see if there’s something transmitted all the way down,” Dr. Barres said.
Other scientists had mixed views about the study. On one hand, they agreed that the researchers used sophisticated methods to survey epigenetic differences in the sperm. But they were wary of drawing broad conclusions.
Dr. John M. Greally, an epigenetics expert at the Albert Einstein College of Medicine, said it was possible that genetic differences between the men were mostly to blame for the differences seen in their sperm.
He also shared a concern with Dr. Bale and Dr. Soubry that the study involved too few men. The differences in such a small sample might have occurred randomly.
“Honestly, I think a lot of what they have is noise,” Dr. Greally said.
That doesn’t mean that Dr. Greally thinks the Danish scientists are wrong, but rather that pinning down the epigenetic effects that fathers pass to their children will take much more work.
“I’d say, let’s do a study of hundreds of people,” Dr. Greally said. “It’s doable. It just requires that we’re bold about doing these things.”