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30.10.18 Long RNA species contribute to intergenerational effects of early life trauma in mice

last modified Oct 30, 2018 08:55 AM
The Miska lab with colleagues in Switzerland show that early life trauma can cause alterations in long RNA in mouse sperm, and this contributes to transmitting the effects to the next generation

Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma

Gapp K et al. (2018) Molecular Psychiatry; 30 Oct. DOI: 10.1038/s41380-018-0271-6


Reproduced from press release from University of Cambridge

Evidence has been building in recent years that our diet, our habits or traumatic experiences can have consequences for the health of our children – and even our grandchildren. The explanation that has gained most currency for how this occurs is so-called ‘epigenetic inheritance’ – patterns of chemical ‘marks’ on or around our DNA that are hypothesised to be passed down the generations. But new research suggests, however, that one way that environmental effects are passed on may in fact be through molecules produced from the DNA known as RNA that are found in a father’s sperm.

In a study carried out in mice, researchers at the Gurdon Institute's Miska lab, in collaboration with the lab of Professor Isabelle Mansuy from the University of Zürich and Swiss Federal Institute of Technology, report how the ‘memory’ of early life trauma can be passed down to the next generation via RNA molecules carried by sperm.  

Dr Katharina Gapp from the Gurdon Institute, with the Mansuy lab, have previously shown that trauma in postnatal life increases the risk of behavioural and metabolic disorders not only in the directly exposed individuals but also in their subsequent offspring. 

Now, the team has shown that the trauma can cause alterations in ‘long RNA’ (RNA molecules containing more than 200 nucleotides) in the father’s sperm and that these contribute to the inter-generational effect. This complements earlier research that found alterations in ‘short RNA’ molecules (with fewer than 200 nucleotides) in the sperm. RNA is a molecule that serves a number of functions, including, for some of the long versions called messenger RNA, ‘translating’ DNA code into functional proteins and regulating functions within cells.

Using a set of behavioural tests, the team showed that specific effects on the resulting offspring mediated by long RNA included risk-taking, increased insulin sensitivity and overeating, whereas small RNA conveyed the depressive-like behaviour of despair. 

Dr Gapp said: "While other research groups have recently shown that small RNAs contribute to inheritance of the effects of chronic stress or changes in nutrition, our study indicates that long RNA can also contribute to transmitting some of the effects of early life trauma. We have added another piece to the puzzle for potential interventions in transfer of information down the generations."

Gapp Fig 1 sperm long rna

Fig 1 shows the experimental protocol.


Abstract from the paper

Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences.

Here we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk taking in adulthood whereas the small RNA fraction alters body weight and behavioral despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.


Read more about research in the Miska lab.

Watch Eric Miska describe his research on video.

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Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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