The age of the father plays a role in pregnancy outcomes, with harmful genetic changes in sperm being substantially more common in older men, new research shows.
Along with a steady build-up of random changes in DNA as men got older, the researchers also discovered the increase in mutations is due to a subtle form of natural selection, with some mutations having a competitive edge during sperm production in the testes, according to a report in Nature.
In 81 healthy volunteers, researchers found that approximately 2% of sperm from men in their early 30s carried disease-causing mutations, compared to 3% to 5% of sperm from men ages 43 to 74, and 4.5% of sperm from 75-year-olds.
Some of the mutations have been previously linked to cell growth and development, while others are associated with severe neurodevelopmental disorders in children and inherited cancer risk, the researchers noted.
Others may impair fertilization, embryo development, or result in pregnancy loss, they said.
“Some changes in DNA not only survive but thrive within the testes, meaning that fathers who conceive later in life may unknowingly have a higher risk of passing on a harmful mutation to their children," Professor Matt Hurles of the Wellcome Sanger Institute in Hinxton, England, said in a statement.
In a complementary study involving over 54,000 parent–child trios and 800,000 healthy individuals, also published in Nature, some of the same researchers analyzed mutations already passed on to children, rather than those measured directly in sperm.
They identified more than 30 genes where mutations give sperm cells a competitive edge via natural selection, again including many linked to rare developmental disorders and cancer. Many such mutations overlap the set of genes observed directly in sperm.
The work highlights how natural selection within sperm can be directly observed in the DNA of children, influencing their chances of inheriting certain genetic disorders, the researchers said.
"Our findings reveal a hidden genetic risk that increases with paternal age,” Hurles, who co-authored both studies, said.