Stress alters the expression of small RNAs in male mice and leads to depressive behaviours in later generations.
Trauma is insidious. It not only increases a person’s risk for psychiatric disorders, but can also spill over into the next generation. People who were traumatized during the Khmer Rouge genocide in Cambodia tended to have children with depression and anxiety, for example, and children of Australian veterans of the Vietnam War have higher rates of suicide than the general population.
Trauma’s impact comes partly from social factors, such as its influence on how parents interact with their children. But stress also leaves ‘epigenetic marks’ — chemical changes that affect how DNA is expressed without altering its sequence. A study published this week inNature Neuroscience finds that stress in early life alters the production of small RNAs, called microRNAs, in the sperm of mice (K. Gapp et al. Nature Neurosci. http://dx.doi.org/10.1038/nn.3695; 2014). The mice show depressive behaviours that persist in their progeny, which also show glitches in metabolism.
The study is notable for showing that sperm responds to the environment, says Stephen Krawetz, a geneticist at Wayne State University School of Medicine in Detroit, Michigan, who studies microRNAs in human sperm. (He was not involved in the latest study.) “Dad is having a much larger role in the whole process, rather than just delivering his genome and being done with it,” he says. He adds that this is one of a growing number of studies to show that subtle changes in sperm microRNAs “set the stage for a huge plethora of other effects”.
In the new study, Isabelle Mansuy, a neuroscientist at the University of Zurich, Switzerland, and her colleagues periodically separated mother mice from their young pups and exposed the mothers to stressful situations — either by placing them in cold water or physically restraining them. These separations occurred every day but at erratic times, so that the mothers could not comfort their pups (termed the F1 generation) with extra cuddling before separation.
When raised this way, male offspring showed depressive behaviours and tended to underestimate risk, the study found. Their sperm also showed abnormally high expression of five microRNAs. One of these, miR-375, has been linked to stress and regulation of metabolism.
Written By: Virginia Hughes
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