Male mice's deficient diet is linked to birth defects
15 Dec 2013
The Washington Post Sunday
BY MEERI KIM Kim is a freelance science journalist based in Philadelphia.
"We should be looking carefully at the way a man is living his life." Sarah Kimmins, study author and reproductive biologist
Watching what you eat and drink isn't just for moms-to-be anymore. New scientific evidence suggests that the father's diet before
conception might be just as important to a child's health.
A study in mice linked nutritional deficiencies in paternal diet to a higher rate of birth defects compared with those whose fathers were
fed a normal, well-rounded menu. The findings raise concerns about dads unknowingly passing on harmful traits through molecular markers
on the DNA of their sperm.
These epigenetic markers don't change the genetic information, but rather switch parts of the genome on and off. They are susceptible to
environment and diet throughout fetal development but were thought to be wiped clean before birth. New studies, including the one published
online Tuesday in Nature Communications, have revealed that some of them may survive all the way from sperm to baby.
When analyzing the sperm epigenomes of the low-nutrition mice, the researchers found abnormalities in epigenetic markers that affected
genes linked to development, neurological and psychological disorders and certain cancers.
"We should be looking carefully at the way a man is living his life," said study author and reproductive biologist Sarah Kimmins of McGill
University. "Environmental exposure is remembered in the developing sperm and transmitted to offspring."
Since it takes human males about three months to produce fully grown sperm from stem cells, Kimmins speculates that men trying to have
children could try cleaning up their diets even temporarily.
"If a man has been living a bad, unhealthy lifestyle, he will not only improve his own health but the health of his offspring," she said.
Scientists at McGill fed male mice a diet containing less than 15 percent of the recommended amount of folate, otherwise known as
vitamin B9. High doses of the nutrient can be found naturally in liver, spinach, brussels sprouts, asparagus and avocados. Kimmins
chose folate because it can directly affect the body's ability to produce epigenetic markers.
In 1998, the Food and Drug Administration started to require makers of grain products to enrich breads, pastas, rice and cereals with
folic acid, the synthetic form of B9. Most people in the United States get enough of the vitamin, but some groups such as younger
women tend to absorb less of it. Also, being overweight or consuming alcohol can cause the body to metabolize less folate.
Babies of women who don't get enough folate are more likely to have defects in the neural tube, a structure in embryos that later becomes
the brain and spinal cord. While it was known that low folate in males can affect their fertility, these findings show a surprising
association with birth defects.
"No one ever thinks of birth defects as coming from the father if they aren't genetic," said Kimmins. Instead, the focus tends to be
entirely on the mother and what she eats and drinks because of the shared nutrients during pregnancy. "This is becoming a really
outdated way of thinking," she said.
One of every 33 children in the United States is born with a birth defect, according to the Centers for Disease Control and Prevention,
but most of those have an unknown, nongenetic cause. Some scientists suggest that the inherited layer of epigenetic information could
contribute to birth defects.
Kimmins and her colleagues set out to discover whether they could change the information transmitted by sperm without altering the DNA
itself, by tweaking only food intake.
Male mice in one group were fed a folate-deficient diet from womb to adulthood, because sperm cells start to form when pups are still in
utero. The control male mice, as well as the females that both groups bred with, were kept on normal, wellbalanced diets.
The folate-deficient fathers had fertility issues, as expected, and their litters had almost 30 percent more birth defects than the
control group's.
"The birth defects were quite severe: club foot, underdeveloped digits, shortened jaws, webbing of the digits," Kimmins said. "I didn't see any of that in the controls."
When analyzing the sperm epigenome of the mice, researchers found differences between the two groups that affected genes linked to
development, the nervous system and cancer.
Kimmins is now working with fertility clinics to gather human data on paternal folate levels, obesity and the sperm epigenome in order to
link them with reproductive success and child health. She expects the results to translate from mice to men, because they are genetically
and epigenetically very similar.
Ohio University endocrinologist Felicia Nowak called the study "a very nice piece of the transgenerational epigenetic puzzle."
Nowak's preliminary results on mice fed high-fat diets reinforce the importance of dads-tobe watching what they eat. Male mice who noshed
on too many fatty foods fathered heavier pups with higher percentages of body fat compared with their low-fat-diet counterparts, even
though all the pups were kept on the same healthy diet.