When it comes to making babies, everybody knows that a mother’s lifestyle matters. During gestation, a mother’s habits and nutritional status can have powerful effects on the way a baby develops. Folate, for instance, is so important for brain development and the prevention of birth defects that the U.S. Center for Disease Control recommends that every woman of child-bearing age get 400 micrograms of folate (also called “folic acid”) each day. Establishing a history of good nutrition before conception helps ensure that a fetus has what it needs during the crucial, early weeks of pregnancy.
But what about fathers? Conventional wisdom suggests that men don’t have to worry as much about their lifestyle choices. Sure, some things, like smoking, can have a negative impact: Exposure to second-hand smoke increases the risk of miscarriage and birth defects. But doctors haven’t paid much attention to what fathers-to-be eat and drink. And that should change.
Take the latest study of folate deficiency in mice. Romain Lambrot and his colleagues bred a group of male mice with insufficient levels of dietary folic acid. Then they mated these males with healthy, nutritionally-replete females, and monitored the results.
Two things happened. First, there were fertility problems. The rate of pregnancy by folate-deficient males was only 52%, compared with 85% for normal males. Second, when babies were conceived, there were more birth defects.
“We were very surprised to see that there was an almost 30 per cent increase in birth defects in the litters sired by fathers whose levels of folates were insufficient,” Lambrot says in this press release. “We saw some pretty severe skeletal abnormalities that included both cranio-facial and spinal deformities.”
The photograph here, courtesy of Lambrot, shows some of these differences. The mouse pup on the left, sired by a folate-sufficient father, is developmentally normal. The pup on the right, sired by a folate-deficient dad, has skull abnormalities.
How is this possible? Until recent decades, scientists thought of the male contribution to fertilization in terms of DNA alone, so it was hard to see how something like paternal diet could influence prenatal development.
A male might alter the DNA in his sperm by exposing himself to harmful, mutagenic radiation, and the results could get passed onto offspring. Alternatively, a male could change the course of a pregnancy by exposing the mother to environmental toxins (like secondhand smoke) or subjecting her to stress and abuse. But barring those kinds of scenarios, it wasn’t clear that male behavior — before or around the time of conception — could make much difference.
But now we know that DNA is often wrapped — quite literally — in molecules that have the power to switch genes on or off. These wrappers make up your “epigenome,” a collection of chemical compounds that tell your genes what to do. And what’s so interesting about the epigenome is that (1) it is influenced by environmental factors, including stress, diet, and drug use; and (2) it can get passed from parent to offspring.
So if folate, or a lack of folate, triggers changes in a man’s epigenome, these changes might end up in the man’s sperm and become part of the new baby’s epigenome as well. In the mouse study, Lambrot’s team analyzed sperm and confirmed that folate-deficient males showed epigenetic changes for a number of genes, including genes associated with brain development and various life-threatening diseases. But the researchers didn’t find direct evidence that the babies’ epigenomes were similarly altered. They think such evidence may emerge in future studies.
Meanwhile, it seems pretty clear that paternal folate deficiency resulted in a higher rate of birth defects, and the researchers think this should be a warning call for human fathers-to-be. “Our research suggests that fathers need to think about what they put in their mouths, what they smoke and what they drink and remember they are caretakers of generations to come,” says study coauthor Sarah Kimmins. Indeed, new discoveries in epigenetics suggest that we all have the power to safeguard the health of subsequent generations, if we make the right choices.
For more information about epigenetics and the influence of fathers’ lifestyles on offspring, see my post, “Weird science: Your early life stress can reprogram your kid’s DNA.”
Photo: US Navy Mass Communications Specialist 1st Class Leslie L. Tomaino