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Birth defects caused by markers on DNA

Father’s diet may affect offspring

The Washington Post

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 B-9. 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 B-9. Most Americans 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 do not 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, well-balanced 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-to-be 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.