Fathers may be able to pass on the enhanced learning ability that comes from being physically and mentally active through molecular changes in their sperm, according to new research from Germany.
In a paper published in the journal Cell Reports, researchers from the German Center for Neurodegenerative Diseases (DZNE) and the University Medical Center Göttingen, also in Germany, explain how they came to this conclusion after studying mice.
They found that exposure to a stimulating environment with lots of exercise not only increased learning ability in adult male mice, but also that this benefit was inherited by their offspring.
Further tests revealed that the effect was passed on through changes in RNA molecules in the fathers' sperm.
The researchers identified two specific microRNA molecules — called miRNA212 and miRNA132 — as being primarily responsible. MicroRNAs are a group of molecules that control gene activity without changing the underlying DNA.
The new study provides further evidence of an "epigenetic" process of inheritance in which skills can be passed on to the next generation without involving DNA.
In their paper, senior study author André Fischer, a professor in the Department of Psychiatry and Psychotherapy at the DZNE, and his colleagues recap on recent evidence of "non-genetic mechanisms" of inheritance.
The mechanisms concern the emerging field of epigenetics, in which scientists are collecting more and more evidence of how environmental factors — such as lifestyle and diet — of one generation affect biological development, health, and disease of the next generation.
Epigenetic mechanisms alter gene expression without altering DNA. They influence cell activity by switching genes on and off and changing patterns of protein production, for example.
Recent studies suggest that epigenetic changes can be passed on through sperm. Research that was recently presented at a conference, for instance, showed that exposure to a lifetime of mild stress can alter sperm in male mice in such a way that it shapes brain development in their offspring.
Exercise and 'synaptic plasticity'
Prof. Fischer and colleagues note that physical exercise combined with cognitive training — which they refer to as "environmental enrichment" — is known to lower the risk of various diseases, including those that affect the brain.
In particular, studies in rats and humans have demonstrated that environmental enrichment can boost "synaptic plasticity," which determines how well brain cells communicate and is also recognized as the biological basis of learning.
However, while studies have also revealed that raising mice in enriched environments can lead to enhanced synaptic plasticity in their offspring, it is not clear whether this is also true if the exposure only occurs in adulthood.
In addition, the mechanism through which the increased synaptic plasticity is inherited is poorly understood, note the authors.
For their study, the scientists took two groups of male mice. They allowed one group to experience environmental enrichment, which included plenty of exercise, for 10 weeks, while the other group remained in "home cages."
They discovered that compared with the caged mice (the controls), the mice that had experienced environmental enrichment showed a "significant increase" in synaptic activity in the hippocampus, which is an area of the brain that is important for learning.
Benefit is passed on through sperm RNA
In the next phase of the study, the researchers took another two groups of adult male mice and put them through the same regimen, except that after 10 weeks, they mated them with home-caged females.
The team's results revealed that the offspring of the male mice that had experienced environmental enrichment in adulthood also had increased hippocampal synaptic activity, compared with the offspring of the male controls.
The authors note that since the mothers had never experienced environmental enrichment, the benefit must have passed down through the fathers.
In further experiments, they extracted RNA from the fathers' sperm and injected it into fertilized mouse egg cells.
It was discovered that offspring from eggs with sperm RNA of mice that had been exposed to environmental enrichment during adulthood had "enhanced synaptic plasticity and learning ability" compared with offspring from eggs with sperm RNA from control mice.
The researchers concluded that environmental enrichment, or being more physically and mentally active, in adulthood can boost cognitive ability in offspring, and that this is passed on through sperm RNA.
Using more precise injections of RNA, the team then sought to identify the exact RNA molecules responsible for the epigenetic inheritance of the enhanced learning ability. They found that miRNA212 and miRNA132 accounted for most of it.
"For the first time, our work specifically links an epigenetic phenomenon to certain microRNAs."
Prof. André Fischer