Stress in early life can alter the production of small sections of the genetic material RNA in the sperm of mice, affecting behaviour not only in the mice themselves but also in their offspring, research suggests.
Researchers at the University of Zurich 'traumatised' male mice by separating them from the mother at unpredictable times in the first two weeks of life. When these young mice because adults, they were less hesitant to enter open spaces and brightly lit areas than mice that had not been separated from their mothers.
These behavioural changes were also present in the mice's offspring, which also displayed alterations in metabolism, and in their offspring's offspring.
'We were able to demonstrate for the first time that traumatic experiences affect metabolism in the long-term and that these changes are hereditary', said Professor Isabelle Mansuy, who led the study.
'What it's doing is building on the notion that dad's contribution is actually more than just his genes when he fertilises the oocyte,' said Professor Stephen Krawetz from Wayne State University, who studies RNA in sperm but was not involved in the study. '[It] really adds a new dimension in terms of what impact dad can have'.
The question of how epigenetic changes are passed on through sperm continues to be a matter of debate, with one proposed mechanism centering on alterations in the levels of small non-coding RNAs called micro RNAs (miRNAs) in sperm. These miRNAs turn down the expression of specific target genes, potentially causing long-lasting changes in gene expression.
In this latest study, researchers found increases in several miRNAs in the sperm of traumatised mice. The same changes were also observed in the hippocampus (the area of the brain usually associated with stress sensing) in their offspring.
To see whether these alterations could be responsible for the abnormal behaviour in the next generation, the scientists isolated RNA from the sperm of traumatised mice and injected it into an egg that had already been fertilised, excluding any effects due to changes to the DNA of the sperm.
They found that the resulting mice developed the same behavioural and metabolic abnormalities as the natural offspring of the traumatised mice, suggesting that these effects were transmitted through miRNA in the sperm.
'That was the best and most causal evidence we could provide', said Professor Mansuy.
Nonetheless, the authors admit that many questions are still to be answered. It is not known how stress in early life can induce these miRNA changes in sperm, or how these changes cause the behavioural effects in the offspring.
Dr Minoo Rassoulzadegan, a geneticist at the University of Nice who advised the researchers but was not herself an author, commented: 'This is the question for the future, to find out what [the RNA] is doing to the genome'.