The rate of birth defects was 28 per cent higher per litter of baby mice if their fathers were fed a diet deficient in vitamin B9 or folate compared to litters where both parents were fed a healthy diet, reported the study published Tuesday in the journal Nature Communications.
Folate, found in leafy green vegetables, cereals, fruit, beans and liver, is known to prevent miscarriages and birth defects in humans if taken by the mother. Because of that, folate supplements are often recommended for women of childbearing age, especially if they are trying to become pregnant, and a lot of processed food is now enriched with folate. In men, folate deficiency is already known to reduce fertility.
However, many human populations, such as those in Canada's North, still don't have enough folate in their diets, said Sarah Kimmins, associate professor of reproductive biology at McGill and the senior author of the new study.
Recent research also suggest that obesity, which affects about 25 per cent of the Canadian population, can impact the way the body handles folate, reducing its absorption into the bloodstream.
Kimmins, who holds a Canada Research Chair in epigenetics, reproduction and development, noted that mice are genetically very similar to humans. She added that the mechanism that appears to link a father's diet and his offspring's health works the same among mice and humans.
Birth defect prevention now targets moms
She suggested the findings therefore have implications for public health messages about the prevention of birth defects, which currently target mothers exclusively.
"There's a perception that's no longer true, that really needs to be challenged, that the father can do whatever he wants in terms of what he eats, what kind of lifestyle he lives, whether he takes drugs or not, and this isn't going to affect whether he has a healthy child or not," she said.
"Our research really shows that this isn't the case — men really need to think carefully about the life they're living because there is a potential for an impact on the offspring."
Kimmins said she and her colleagues were interested in looking at the effect of fathers' diet on their offspring because some recent epidemiological studies on humans suggested that what a person's father or grandfather ate may affect his or her health.
What Kimmins wanted to find out is how that might work.
She and her colleagues set up an experiment where all the female mice were fed a healthy diet of food pellets with enough folate. They were mated with 35 male mice who were also fed a healthy diet and 32 who ate pellets low in folate, designed to mimic a typical folate-deficient diet in humans.
Kimmins was interested to see how that would affect the epigenome — markers in the DNA that turn genes up or down that can be affected by the environment and are copied along with the DNA every time a cell divides.
Researchers already knew that folate is one chemical used to generate those epigenetic markers.
The researchers examined the sperm of the males fed the folate deficient diet, and sure enough, they found the epigenetic markers were affected for genes linked to development and diseases such as cancer, diabetes, autism and schizophrenia.
They also found some changes in the epigenetic markers in the placenta, the organ that nourishes the fetus during pregnancy and contains the same genes as the fetus itself.
"And then we were shocked when we found this increase in incidence of birth defects," Kimmins said, adding that a link between a father's diet and birth defects had never been reported before.
Among the 328 mice born to fathers with the folate-deficient diet, 14 had birth defects including muscle and skeletal defects, face and skull abnormalities, small lower jaws and webbed or fused digits.
There were only three minor defects among the 285 mice whose fathers had a healthy diet.
Human tests next
"I'm certainly confident that we need to move forward as soon as possible with this work to validate in humans," Kimmins said. "It's too important not to."
She noted that right now one in 33 children are born with a birth defect and half the time, the cause is unknown. It's possible that targeting fathers could help prevent some of those defects.
Kimmins said her research group is planning to work with fertility clinics to look at how men's folate levels – and obesity that can affect folate absorption – affect the risk of birth defects among their children.
Many questions remain, such as how long environmental factors such as levels of folate in a male's diet will affect the sperm.
Kimmins said it takes about three months for each sperm cell to develop and mature, even though thousands are produced at any given moment.
"Potentially you could clean up life for three months and maybe that would allow you to make the healthiest sperm possible," Kimmins said. "But we don't know how reversible any damage is … that's something we need to figure out."