Fathers’ age and its possible impact: an Australian summary
With the average age of childbearing for men and women rising over recent decades, the media often focuses on how a mother’s age can affect the health of her baby. But a growing body of research suggests prospective fathers’ age can also increase a child’s risk of developing certain conditions.
Professor John McGrath, a psychiatrist and epidemiologist from the Queensland Brain Institute at the University of Queensland is one of a growing number of researchers investigating a link between older fathers and neurological conditions including schizophrenia and autism in their children.
In Australia, around one child in 100 will develop autism; figures are similar for schizophrenia. McGrath has been looking into factors that increase a person’s risk of developing these and other neurological conditions. Over the past decade or so, he has found strong links between a fathers’ age at conception and a number of neurological conditions.
So far, research has linked older fathers with autism, schizophrenia, bipolar disorder, as well general cognitive development in children. But the precise risk of these conditions developing in children of older fathers has not been calculated, and other predisposing genetic and environment factors are likely to play a role.
In 2012, a team of researchers published a study in the prestigious journal Nature, describing how de novo mutations increase with a father’s age. The researchers sequenced the entire genomes of 78 mother-father-child trios from Iceland. The children of these trios had either autism or schizophrenia, but the parents had neither. After comparing the de novo mutations in these children with the genomes of close to 2000 healthy Icelanders, the researchers concluded that around 97 per cent of these mutations came from the fathers.
The researchers estimated that the number of mutations a man is likely to pass on doubles every 16.5 years. At 20, a man will pass on roughly 25 mutations; at 40, the number will be about 65. In contrast, the average number passed on by mothers is just 14, regardless of age.
Another 2012 study calculated that mutations leading to autism were four times more likely to come from the father than the mother.
It is not clear why a father’s age is linked to later development of neurological conditions in particular, but McGrath told ABC Health and Wellbeing he suspects these disorders could be the “canaries in the gold mine”.
“It could well be that there are other disorders that are also linked to father’s age, but no-one’s really done the studies yet,” he said.
Lifestyle and environment can also influence sperm quality, Dr Mark Green, a reproductive biologist at the University of Melbourne told ABC. “Males do keep producing sperm,” he said, “but what kind of sperm, and what kind of quality?”
Years of exposure to environmental toxins such as pesticides, paint strippers and other chemicals could be having more subtle effects on the way in which genes within the sperm are tagged and used later on. These so-called epigenetic changes don’t alter the genetic sequence within the sperm, but may alter when and where genes are switched on or off during foetal development.
Green and his colleagues are currently investigating how these epigenetic changes in the sperm of mice effect male fertility and the health of the resulting embryos conceived with these sperm.
De novo mutations and epigenetic changes could both be contributing factors in another recent study linking a father’s age to stillbirth, pre-term birth and low birth weight.
So what’s the advice for prospective parents?
McGrath doesn’t think couples necessarily should start having babies at a younger age: “We’re not ready to give strong advice to prospective parents about what the optimal age for men to have their children is.”
“The increased risk is quite small in the universe of risks that we take every day. There are many other things that may be more potent risk factors than this risk of advanced paternal age.”
Factors such as improving your diet, getting more exercise, and cutting down on cigarettes and alcohol can help to improve a man’s sperm quality. And the good news is it only takes around three months for these changes to have an impact. Green told ABC it is important for older men to make these lifestyle changes before trying to conceive and welcomed the shift in emphasis away from women bearing the sole responsibility for a baby’s health during pregnancy.
“It’s not all about what your partner’s eating or drinking. It’s what you’re doing as well.”
“You can definitely improve your chances of conceiving,” said Green, “but not just that, the quality of your sperm, and the quality probably of that child.”
A few facts about sperm
When a man goes through puberty, a sperm production line within his testes is set in motion and it continues pumping out millions of sperm each day until he dies.
The raw materials that feed this voracious sperm factory are sperm precursor cells, called spermatogonia. Every 16 days, spermatogonia diligently copy their genetic material and divide into two identical cells. One cell will be fed into the 74-day-long manufacturing line to become a mature sperm, while the other will continue to copy and divide to ensure a constant supply of sperm for the future.
By the time a man reaches 20 his spermatogonia have already been through around 200 rounds of cell replication, and approximately 660 by age 40. This wouldn’t be a problem if the process worked perfectly every time. But it doesn’t.
Each round of replication brings with it the chance of an error being introduced, in the form of a mutation. Just as a typist transcribing a book might inadvertently introduce a typo, the cellular replication machinery that copies the genetic material within a spermatogonial cell is also fallible.
When a mutation occurs in a sex cell, such as a sperm or egg, the mutation (called a de novo mutation) can potentially be passed on to a baby.
While many of these mutations are completely harmless, the number of them increases as men age – this also increases the risk of one of these mutations causing havoc.
Adapted from Dads’ biological clocks tick too by Dyani Lewis in ABC Health and Wellbeing, 17 October 2013. Click here for the original article.Tags: child health, Fatherhood research, genetics, older fathers