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expert reaction to study looking at epigenetics in mice and the influence of exercise on the cognitive abilities of offspring

A new study, published in Cell Reports, examines whether exercise, through epigentic effects, can have a cognitive benefit on the health of future offspring of adult male mice.


Dr Jon Houseley, Principal Investigator in Epigenetics, The Babraham Institute, said:

“Benito et al’s work implies the existence a mechanism in mice that connects an adult male’s environment to the neural development of his offspring. Intuitively it makes sense for parents to pass information about the environment to their offspring, but this does not fit well with classical models of inheritance and the existence of such processes in mammals remains controversial.

“The results of this study suggest that mice born to fathers in complex environments will be more mentally agile than those in simpler surroundings, and highlight RNA molecules present in sperm that mediate this change. While it agrees with other recent work in the field, this research leaves major questions unanswered – how is the complexity of the environment communicated from the brain to the germline to change the RNA component of sperm, and how do RNA molecules alter neural development?

“Nonetheless, this work adds to accumulating evidence that epigenetic inheritance mechanisms are active and important in mammals. It seems unlikely that these particular RNA molecules will also communicate environmental information across generations in humans, however understanding such inheritance mechanisms in mice suggests ways in which environmental information may be passed to our own children.”


Prof. Eric O’Neill, Associate Professor, CRUK/MRC Oxford Institute, said:

“The study raises an interesting concept of transgenerational transition of fitness attributes linked to small RNA species in the sperm of fathers. The transgenerational transition of parental environmental and social exposures, such as to famine or war, have been proposed to be passed on to subsequent generations via epigenetics. However, the results here are limited to very small observations in a small number of mice. As such, the results, although potentially interesting, do not represent sufficient evidence to support a conclusion that this is a robust phenomenon or translatable to humans.”


Prof. Marcus Pembrey, Emeritus Professor of Paediatric Genetics, UCL Great Ormond Street Institute of Child Health, said:

“This thorough mouse experiment is an important step in unravelling what, if anything, contributes to an individual’s intelligence beyond genetic inheritance and learning after birth. Using physical and mental exercise to fine-tune the brain’s ability to learn (i.e. enhance synaptic plasticity) of male mice, they show the offspring (of both sexes) inherit this enhanced synaptic plasticity regardless of exercise.  If this system of the offspring inheriting a ‘head start’ applies to humans, it might help to explain the so-called Flynn effect where the population IQ in industrial societies has risen every decade for the last century.

“The authors chose to start with male mice because sperm are more readily available than eggs; a practical point that would apply when doing similar studies in humans. Sperm carry the DNA and its variations within a single set of paternal chromosomes, but they also carry free-lying molecules called microRNAs. A single type of microRNA can modify the activity, or influence the impact of, large sets of different genes. Whilst this mouse experiment was able to identify a key microRNA (miR212/132) in the transmission of the enhanced synaptic plasticity, the authors admit we are a long way from fully understanding the causal pathways. How do optimal levels of this microRNA relate to physical and mental exercise, how and when do these molecules get into sperm, let alone how they impact embryological development of the offspring’s brain.

“It was a pleasure to see a study of inheritance of enhancement of brain function rather than damage and disease!”


Prof. Simon Fishel, Founder and President, CARE Fertility, said:

“This is a fascinating study in mice providing further increasing evidence of how we conduct our lives before we conceive our children may have consequences for our offspring. In this study, which looks solely at adult male mice (i.e. of reproductive potential) and concludes that mice provided with environmentally enhanced opportunity produce small molecules, called ‘microRNAs’, that can be passed on to sperm and when these sperm bring about fertilisation pass on to the pup enhanced cognitive ability over controls.

“This is a complex scientific study that is well-conducted and presented and opens up further the enthralling study of a ‘transgenerational inheritance’; by which parental inheritance is not only generated by the conventional DNA genetic code already present and fixed in our gametes, but an inheritance that can modify an offspring’s health and functions according to how the male (in this case) lives life!

“However, there is much work to do to understand if this study can not only be replicated in mice, but other mammalian species too, and ultimately in humans. The authors have been very clear that the work is focused solely on mice, and much needs to be done to understand if there will be any relationship to reproductive medicine.”


* ‘RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment’ by Eva Benito et al. published in Cell Reports on Tuesday 10th April. 


All our previous output on this subject can be seen at this weblink:


Declared interests

Dr Jon Houseley: I am a Wellcome Trust Senior Research Fellow at a BBSRC-funded Research Institute, and my research aims to determine how cells modify genetic inheritance in response to the environment.

Prof. Marcus Pembrey: No relevant declarations of interest

Prof. Simon Fishel: “Minor shareholder in CARE Fertility.”

None others received.

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