A new study, published in Nature Neuroscience, has shown that traumatic experiences early in the life of mice alters the expression of small RNAs in the sperm. The depressive behaviors seen in the father are also present in the offspring, persisting for several generations.
In recent years it has become apparent that it is not only our DNA that contributes to heritability; environmental factors evidently also play a role. Observations that individuals who have experienced trauma often have children that also display particular behavioral traits, such as depression and anxiety, led researchers to believe that there may be more to the story than purely social explanations. Of course, individuals that have experienced trauma may behave differently toward their children which could provide some explanation for the apparent effects, but it is evident that stress can also affect epigenetics. Epigenetics refers to alterations in the expression of genes which are not due to changes in the sequence itself.
In this new study scientists wanted to investigate how stress early in the life of mice affects the behavior of their offspring, and also how it can alter expression of a particular type of RNA found in sperm. Recent evidence has suggested that small non-coding RNAs, which are RNA molecules that aren’t used to make protein, are abundantly expressed in the sperm of mammals, and that they may mediate inheritance of traits. It is not known, however, whether stress can influence the expression of these RNAs.
Researchers from the University of Zurich exposed young mice to traumatic stress by unpredictably separating them from their mothers and also exposing the mother to stressful situations, such as placing them in cold water.
Unsurprisingly these male offspring, termed the F1 generation, displayed depressive behaviors. But the team also found that their sperm contained abnormally high levels of five microRNAs (miRNAs), which are a type of small non-coding RNA. In particular, one of these miRNAs has been previously associated with stress. Not only that, but the blood and hippocampus were also found to display abnormally high expression of these 5 miRNAs.
The team then investigated the offspring of the F1 males, called the F2 generation. They also displayed depressive behaviors and had high levels of the same miRNAs in the blood and hippocampus. The offspring of these males, the F3 generation, once again displayed depressive behaviors. Intriguingly, however, miRNA expression in the sperm of the F2 and F3 males was unaffected, suggesting another epigenetic mechanism may be at play.
Since it remained a possibility that the observed effects could be explained by social factors, the team isolated RNA from the sperm of traumatized males and injected it into the eggs of mice that had not been traumatized. This reproduced the depressive behaviors in the offspring, and also the offspring of these mice.
The team are now investigating the expression of similar miRNAs in humans that have experienced trauma and also the children of these individuals. According to Isabelle Mansuy, one of the authors of this study, this could possibly be used indicate susceptibility to stress.