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
'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'.