Mothers-to-be have long been warned about drinking alcohol and smoking cigarettes, but men who are trying to have children may want to be just as careful. A growing body of research suggests that what fathers are exposed to in the environment can have lasting effects on their children’s health.
A new report details how various aspects of the father’s life — from alcohol consumption and smoking to age and nutritional status — can influence the offspring’s risk of developing fetal alcohol syndrome, birth defects, autism and other conditions.
The idea that maternal lifestyle and health can influence the fetus has been appreciated for a while, “but nobody thought about fathers because it did not seem there was a logical link between the two,” said Joanna B. Kitlinska, associate professor of biochemistry and molecular and cellular biology at Georgetown University Medical Center. Kitlinska was part of the group of Georgetown researchers who wrote the article (PDF) reviewing previous research, which was published Monday in the American Journal of Stem Cells.
Fathers can increase fetal alcohol risk
In the case of fetal alcohol syndrome, it makes sense that women should not consume alcohol during pregnancy because it crosses the placenta and can result in low birth weight, poor coordination, delays in cognitive development and heart defects.
However, Kitlinska and her colleagues point to research over the past decade suggesting that fathers who regularly consume alcohol before conceiving increase their child’s risk of having fetal alcohol syndrome, even if the mother does not drink before or during pregnancy. Heavy drinking or alcoholism among fathers has been implicated in as many as 75% of affected children.
When men drink alcohol, smoke or engage in other behaviors, it seems to leave a mark on their offspring through epigenetics, the biological processes that tweak genes without mutating them. Alcohol consumption has been associated with an epigenetic change called methylation, which adds to or takes away a molecule called a methyl group that sits on DNA and influences whether genes are active or silent.
Another aspect of paternal health that could have a lasting effect on children, and possibly even on subsequent generations, is obesity. Research has linked obesity among fathers with the addition of methyl groups to genes that play roles in growth and metabolism; the methyl groups were added to genes both in sperm cells and in the offspring.
It is still not clear which genes in particular are affected by shifts in patterns of methylation, Kitlinska said. In many cases, methyl groups — and epigenetic changes in general — that the embryo inherits from the father or mother are “wiped out” as the embryo develops, but certain genes can be imprinted, meaning they preserve the changes through gestation and into childhood.
Methylation could help explain the longstanding mystery of why older men are more likely to have children with autism, schizophrenia and heart defects.
One study found that people diagnosed with schizophrenia were twice as likely to have been born to fathers between 45 and 49 years old and three times more likely to have been born to fathers 50 and older, compared with fathers younger than 25, although the risks of children of older dads were still low. Another study found that children with autism were nearly six times as likely to have fathers who were 40 or older when they were conceived than fathers who were younger than 30 years of age.
Nevertheless, mutations in sperm DNA, which accumulate with age, could also play an important role in increasing the risk of these conditions among offspring. “My feeling, although nothing has been proven, is that the association [with paternal age] is more due to genetic changes,” Kitlinska said.
A better understanding of why fathers matter
For a long time, sperm were considered nothing more than a vehicle for the father’s genes. “It was difficult to think there would be any information in that cell type other than the DNA sequence itself,” said Stephen A. Krawetz, associate director of the C.S. Mott Center for Human Growth and Development at the Wayne State University School of Medicine, who was not involved in the new report.
That all changed when technologies became available that let researchers look in the cell at the genes and the products of those genes, Krawetz said.
In the 1990s, Krawetz and his colleagues realized that sperm contain RNA, which are the intermediary molecules that convert DNA into proteins. That opened the door to the possibility that some of these RNA species could be having epigenetic effects, Krawetz said. Similar to methyl groups, they could be altering the activity of genes without mutating them.
There are hints coming from recent research, which Kitlinska described in her article, that men who smoke have differences in the types of RNA species in their sperm compared with men who do not smoke. These RNA are thought to play key roles in the development of healthy sperm and healthy embryos.
How can fathers protect their sperm?
Research suggests that future fathers can increase the chances of having healthy children through “common sense recommendations” such as not drinking alcohol in excess or smoking, Kitlinska said.
When it comes to paternal age, the rise in risk is gradual. Studies of rates of schizophrenia and autism found that they inched up with every five-year increase in the father’s age at the time of conception.
“With everything, there is a balance in life, because biology tells us to have children earlier, but the social and economic factors promote having children later,” Kitlinska said.
For better or worse, this area of research is underscoring the important role that fathers play in the health of their children even from the earliest moments of development.
“The dad has to assume some of the responsibility, at least 50% of the birth of a healthy child,” Krawetz said.