Genetics and stem cells

Can mental trauma be passed on through sperm?

"Traumatic experiences can be inherited, as major shocks alter how cells in the body work," The Daily Telegraph reports.

But before you start blaming mum and dad for your problems, the research it reports on only involved mice.

The study looked at how traumatic stress in the early life of male mice influenced the genetic material in their sperm.

Researchers “traumatised” male mice during their first weeks of life by separating them from their mother. They then gave the male mice a series of behavioural tests. They found that those separated from their mothers didn’t show a rodent’s natural avoidance for open and brightly lit spaces.

The researchers then extracted sperm from the “traumatised” male mice and found it had several changes to small molecules (RNA) involved in genetic regulation. These molecules are believed to play a role in transferring the effects of our environmental experiences to our DNA.

They then showed the behaviour of offspring was similarly affected purely by injecting the sperm RNA from the traumatised male into an already fertilised egg cell from an untraumatised female. On behavioural tests they found that the offspring displayed the same behavioural tendencies as the “traumatised” male mice.

This suggests that the small RNA molecules could have a role in transferring the effects of traumatic experiences to our genetic material.

While this study may appear to confirm the sentiment of Phillip Larkin’s famous poem, This Be the Verse (in which parents are blamed for the faults of their children using post-watershed language), trying to untangle the genetic as opposed to any environmental parental effects on your current mental health is an extremely complex task.

Where did the story come from?

The study was carried out by researchers from University of Zürich and Swiss Federal Institute of Technology in Zürich, Switzerland, and the Gurdon Institute, Cambridge, UK. The study was supported by the Austrian Academy of Sciences, the University of Zürich, the Swiss Federal Institute of Technology, Roche, the Swiss National Science Foundation, and The National Center of Competence in Research “Neural Plasticity and Repair”. One researcher received funding from a Gonville and Caius College fellowship.

The study was published in the peer-reviewed scientific journal Nature Neuroscience.

The Daily Telegraph and the Mail Online’s reporting of this study was of poor quality. Both news sources gave the impression the research findings could be directly applied to humans.

The Mail in particular gives a very misleading impression, saying that, “children of people who have experienced extremely traumatic events are more likely to develop mental health problems”. They also say that “changes are so strong they can even influence a man’s grandchildren”. Only much further in, the article does correctly begin to discuss the real nature of the research.

Still, these massive leaps towards the implications for humans should not be made from this animal research.

What kind of research was this?

This was animal research aiming to look at how traumatic stress in the early life of a mouse influenced its genetic material. They also looked at how injecting sperm from traumatised males into female eggs cells affected the biological processes and behaviour of the offspring.

The researchers explain that though an individual’s characteristics and risk of diseases are largely determined by their genetics, environmental factors, such as traumatic experiences in early life, can also have an important effect on an individual. How this happens is not known for certain.

This research centred on looking at the possible effect of environmental trauma on what are called small non-coding RNAs (sncRNAs). These molecules are believed to be the intermediary between genes and the environment, and are thought to relay signals from the environment to our DNA, affecting gene activity. Previous research has implicated sncRNAs as the possible cause for the abnormal functioning of genes in many diseases. Furthermore, sncRNAs are said to be abundant in the mature sperm of mammals. So they may have a role in transferring the effects of environmental experiences to the next generation.

What did the research involve?

The researchers began their study by examining the sncRNA of adult male mouse sperm under normal conditions. They identified several groups of sncRNA that mapped to the genetic material of the sperm. They then looked at the effect that traumatic experiences in the early life of the male mouse had on their sperm sncRNA.

These early life traumatic experiences were the unpredictable separation of the male mouse from its mother. Female mice and their offspring were randomly selected to be unpredictably separated for three hours of the day between days one and 14 after birth.

Meanwhile, the group of control animals were left undisturbed.

After weaning, the mice were housed in small social groups of other mice who had been subjected to the same treatment.

The “traumatised” and control male mice were then given a series of behavioural tests. In a maze test they were put on a platform with two open and two closed walls.

The researchers looked at the time it took the mice to enter the open parts of the maze, and observed their body movements such as rearing and protective and non-protective postures. This is based on the mouse’s natural avoidance for open and unknown spaces. They then placed them in a light-dark box, which was split by dividers into light and dark parts, and looked at the time spent in each compartment. This was based on the natural aversion of rodents for brightly lit areas.

Mice who behave “unnaturally” are said to have an “an altered response to aversive conditions"; a possible sign of stress and trauma.

As another test, they observed them swimming and floating when placed in a tank of water from which there was no way to escape. Mice that quickly gave up trying to escape are said to have increased levels of "behavioural despair" – they literally gave up trying to leave the tank.

They also looked at the mice’s metabolism, by measuring their blood sugar and insulin levels, and measuring their calorie intake.

Samples of mature sperm were also extracted from the male mice and the sperm RNA was analysed. The researchers then injected RNA extracted from the sperm of “traumatised” or control mice into fertilised eggs cells. The reason for this was likely to have been an attempt to isolate the effects of the sncRNA, rather than just fertilising “wholesale” with the sperm of the traumatised males.

Not isolating the effects could mean that other genetic material, proteins and molecules could also have had an influence.

The researchers repeated the behavioural tests with the offspring to see if any behavioural traits had been inherited.

What were the basic results?

On the behavioural tests, the researchers found that male mice that had been traumatised were quicker to enter the open spaces than the control mice (they were not displacing the natural fear of unknown spaces).

Similarly, on the light-dark test the separated male mice spent longer in the lit compartments (they were not displacing the natural avoidance of brightly lit spaces).

When placed in the water tank the separated mice spent more time floating rather than swimming compared to the control mice.

The researchers found that the trauma led to changes in many different sncRNAs in the sperm of the young male mice.

On the repeat behavioural tests on the subsequent offspring, the same observed tendencies of the traumatised male mice seem to have been transferred to the next generation. Also the traumatised male mice themselves didn’t seem to have different metabolism from controls, but the next generation seemed to have an increased metabolic rate. They had increased sensitivity to insulin, and lower body weight despite increased calorie intake.

How did the researchers interpret the results?

The researchers conclude that their findings, “provide evidence for the idea that RNA-dependent processes contribute to the transmission of acquired traits in mammals. They underscore the importance of sncRNAs in [sex] cells and highlight their sensitivity to early traumatic stress”.

Conclusion

This animal study supported the theory that small chain RNA molecules may act as the interface between the environment and our genetics.

The researchers found that the sperm extracted from male mice that had been “traumatised” by being randomly separated from their mothers did show several changes to the small RNA molecules.

These traumatised mice also displayed fewer natural mouse tendencies compared to controls – namely, they did not show the natural aversion for open and brightly lit spaces.

These effects did then seem to be transferred into the offspring when some of this sperm RNA was directly injected into already fertilised eggs cells. On behavioural tests the resulting offspring displayed the same behavioural tendencies as the “traumatised” male mice.

This suggests that the small RNA molecules could have a role in transferring the effects of traumatic experiences to the genetic material of mammals which could be passed onto subsequent generations.

However, extrapolating the findings of this highly artificial study into the complex sphere of human emotions and behaviour is unwise.

A direct comparison between mice and humans is difficult. Maternal separation at a young age is only one possibility in a vast multitude of possible stressors that can affect a human.

Similarly, any offspring’s genetic propensity towards behavioural and mental health will also be greatly influenced by the various environmental exposures and events they experience in their own lives.

Overall, this furthers scientific understanding of how small RNA molecules may be involved in transferring the effects of traumatic experiences to our genetic material and how this may then be passed on to subsequent generations.

However, it does not prove that children of men exposed to trauma are more likely to have mental health conditions, as some of the media indicated.


NHS Attribution