Scientists prove that fears and memories can be inherited via sperm
Darwin’s theory of evolution, that of blind mutation and natural selection, is a pillar of modern day science. Yet to many, it remains deeply dissatisfying for one simple reason — it lacks biological provisioning to pass to our children anything that we have won, or lost, by our exertions through the course of life. While scientists have documented numerous cases where the children of significantly traumatized parents have in fact inherited specific predispositions, direct experimental evidence for this phenomenon, and a plausible mechanism, has until now been lacking. Reporting in the current issue of Nature Neuroscience, researchers have now shown that mice can inherit the acquired fears of their fathers through some mysterious reprogramming occurring within the family jewels.
The way that the researchers were able to constrain the range of possible influences of parent upon child, or in this case from mouse to pup, was to separate them entirely by doing artificial insemination. In that way, the only source of information transfer between the two was the sperm itself. The “fear” or at least the “event” that the experimenters chose to transfer was an association of the smell of a chemical known as acetophenone, which was paired with a slightly discomforting electric shock to the their feet. Acetophenone is a commonly used chemical within the larger science of smell that has a citrus, orange-like smell to it. While there is no perfect stimulus (in higher concentrations acetophonone is actually a hypnotic), it is as good as any for the experiments at hand.
When the researchers tested the pups of the traumatized dads for a startle response to different smells, the acetophenone stimulus had a big effect which was not seen in controls. To emphasize here, these pups never actually learned from any previous footshock trials that the acetophonone was bad news, they just somehow knew it because of who there were. If we accept these results at face value, (and there is simply no further progress if we choose not to) than the question becomes, what in the sperm ferries this experience? It is likely that there are many overlapping mechanisms, existing on many levels. First, there could be changes to the actual DNA sequence, or significant tracts of it. One example for this would be by some kind of viral transformation or directed mutation. Second, there could be so called “epigenetic” modifications to the sequence — basically additional bits that get set by various enzymes acting to modify the DNA base pairs. And third, some other chemical influence affecting global properties of the sperm interior, which possibly gets transmitted to the egg along with the raw genetic cargo.
The researchers focused on mechanism number two here, for several reasons. In this case, sperm happen to carry a similar receptor for acetophenone as that which the nose uses to detect it in the first place. Furthermore, they could look for epigenetic modifications to the control region of the actual gene in the sperm which codes for the acetophone detector. The full fate of odorants like acetophenone, once they are inhaled, still remains to be seen. The idea that acetophone gets into the bloodstream and then to the sperm may have a certain appeal, but it is difficult to actually prove that unambiguously without many controls.
The reason a lot of neuroscientists are excited about this work is that the researchers were also able to show that the regions of the pup’s smell-brain (the olfactory glomeruli) that specifically process acetophonone were much larger than normal. These astonishing effects were also found in the grandpups of the original mouse which underwent the fear conditioning. What confounds is that the changes that took place in the sperm, (or gauged another way, the selection from a pre-existing palette of freshly-minted sperm options), have somehow underwritten the construction of the brain in the next generation. Or so it would appear.
So it seems we now have an experimental base established, through which various mechanisms of the transmission of specific experiences to offspring can be further probed. The actual bandwidth, in bits per second, between brain (which presumably acts as the main detector and controller of experienced-based modifications) and balls is not known. There are certainly nerves that feed the gonads, and also various chemicals of influence that are timely spritzed into the bloodstream. Additionally, there can be fine-scale temperature regulation within the deep vaults of the seminiferous tubule file system (the hatchery bank where sperm are halved) that directly bear on the final product.
We should note that beyond the controlled setting of a caged laboratory mouse isolated from nearly every other possible experience in life, such effects would probably be harder to observe. As humans, we absorb and respond to a constant and diverse onslaught of potentially significant stimuli in any given day. Reliably transmitting any one microexperience in isolation directly to our gonads would be difficult to imagine. However, if males did not in fact dump some level of environmental experience into their sperm each day, then what other reason has been offered to date to explain the prolific turnover of these minions?
Or in other words, sperm must retain some adaptive capacity for the transmission of the instantaneous fitness of the larger collective body, at least on the scale of threat, perhaps extending into other pass-fail social trials. In this larger view, it is important to recognize that the mice in these particular experiments could only do just one thing in their entire life — smell acetophonone when shocked, and put that into next generation. That, they seemed to have done.
Happening in humans?
Commenting on the findings, British geneticist Marcus Pembrey says they could be useful in the study of phobias, anxiety and post-traumatic stress disorders.
“It is high time public health researchers took human transgenerational responses seriously,” he said in a statement issued by the Science Media Centre.
“I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”
Wolf Reik, epigenetics head at the Babraham Institute in England, says such results were “encouraging” as they suggested that transgenerational inheritance does exist, but cannot yet be extrapolated to humans.
The gene, inherited through the sperm of trained mice, had undergone no change to its DNA encoding, the team found.
But the gene did carry epigenetic marks that could alter its behaviour and cause it to be “expressed more” in descendants, says Dias.
This in turn caused a physical change in the brains of the trained mice, their sons and grandsons, who all had a larger glomerulus — a section in the olfactory (smell) unit of the brain.
“This happens because there are more M71 neurons in the nose sending more axons” into the brain, says Dias.
Similar changes in the brain were seen even in offspring conceived with artificial insemination from the sperm of cherry blossom-fearing fathers.
The sons of trained mouse fathers also had the altered gene expression in their sperm.
“Such information transfer would be an efficient way for parents to ‘inform’ their offspring about the importance of specific environmental features that they are likely to encounter in their future environments,” says Ressler.
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