National Geographic

Mice Inherit the Fears of Their Fathers

UPDATE (12/1, 2:37pm): This study was just published in Nature Neuroscience; you can read all of the juicy details here.

UPDATE (11/17, 11:22 am): I just published a new post showing how scientists reacted to this study on Twitter, with comments ranging from “awe-inspiring biology” to “deep skepticism.”

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There’s no question that trauma gets handed down from one generation to the next.

In one highly publicized example, researchers in New York studied several dozen women who were pregnant on September 11, 2001, and had been in the vicinity of the terrorist attacks. Some of these women developed post-traumatic stress disorder (PTSD), and this group shows lower levels of the stress hormone cortisol in their saliva than do those who did not develop PTSD. But here’s the rub: At 9 months old, the babies of the women with PTSD have significantly lower cortisol levels than babies of healthy mothers.

In earlier work, the same researchers had reported low cortisol levels in adult children of Holocaust survivors with PTSD. And in yet another study, Kerry Ressler’s group at Emory University showed that the so-called “startle response” to a sudden stimulus — a marker of anxiety — is more pronounced in kids whose mothers were physically abused as children then in those whose mothers were not abused. I could go on.

But how, exactly, does a parent’s stress leave such a deep impression on its progeny?

Part of it is nurture. A parent’s sadness and stress naturally affects how they interact with other people, including their children. The Holocaust study, in fact, found that the survivors with PTSD tended to emotionally abuse or neglect their children. And we know from some remarkable experiments in rats that parental care affects the offspring’s genes: Rat pups that get a lot of licking and grooming from their mothers show distinct changes in their epigenome, the chemical markers that attach to DNA and can turn genes on and off. Neglected pups, in contrast, don’t show these epigenetic tweaks.

Now a fascinating new study reveals that it’s not just nurture. Traumatic experiences can actually work themselves into the germ line. When a male mouse becomes afraid of a specific smell, this fear is somehow transmitted into his sperm, the study found. His pups will also be afraid of the odor, and will pass that fear down to their pups.

“Parents transfer information to their offspring, and they do so even before the offspring are conceived,” said Brian Dias, a postdoctoral fellow in Ressler’s lab, at an engaging talk about this unpublished data on Tuesday at the Society for Neuroscience meeting in San Diego.

And why, evolutionarily, would a parent pass down such specific information? “So that when the offspring, or descending generations, encounter that environment later in life, they’ll know how to behave appropriately,” Dias said.

The researchers made the mice afraid of certain odors by pairing them with a mild shock to the foot. In a study published a few years ago, Ressler had shown that this type of fear learning is specific: Mice trained to fear one particular smell show an increased startle to that odor but not others. What’s more, this fear learning changes the organization of neurons in the animal’s nose, leading to more cells that are sensitive to that particular smell.

Dias trained mice to fear acetophenone — which, according to this chemist, smells “like orange blossom with a bit of artificial cherry” — over three days, then waited 10 days and allowed the animals to mate. The offspring (known as the F1 generation) show an increased startle to acetophenone (with no shock) even though they have never encountered the smell before. And their reaction is specific: They do not startle to a different odor, propanol (which smells like alcohol). What’s more, the researchers found the same thing in the F1 generation’s offspring (known as F2).

The scientists also looked at the F1 and F2 animals’ brains. When the grandparent generation is trained to fear acetophenone, the F1 and F2 generations have more “M71 neurons” in their noses, Dias said. These cells contain a receptor that detects acetophenone. Their brains also have larger “M71 glomeruli,” a region of the olfactory bulb that responds to this smell. “Like father like son, we’re getting some ancestral information,” Dias said. “But how is that occurring?”

His team performed an in vitro fertilization (IVF) experiment in which they trained animals to fear acetophenone and then 10 days later harvested their sperm. They sent the sperm to another lab across campus where it was used to artificially inseminate female mice. Then the researchers looked at the brains of the offspring. “What is striking is that the neuroanatomical results still persist after IVF,” Dias said. “There’s something in the sperm.”

I’ve been to a lot of scientific talks. The excitement around this one was notable, with many scientists whispering about it in the room and more loudly buzzing in the hallways outside.

But I know what you’re wondering. It was the first question that Dias received from the audience after the talk: “Do you have any idea of how this information being stored in the brain is being transmitted to the gonads?” the questioner asked.

The short answer is that the researchers don’t have any idea, though they’ve thought about several possible explanations. Apparently a study in cats and pigeons showed that after smelling an odor, the odorant receptor molecules can get into the blood stream, and other studies have reported odorant receptors on sperm. So maybe the odor molecules get into the bloodstream and make their way to sperm. Another possibility is that microRNAs — tiny RNA molecules involved in gene expression — get into the bloodstream and deliver odor information to sperm.

For now, though, Dias said, “those are two science-fiction hypotheses.”

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Read more about Ressler’s work in a feature on stress and resilience that I wrote for Nature last year.

There are 19 Comments. Add Yours.

  1. Mike Lewinski
    November 15, 2013

    Fascinating!

    Speculation is fun. I wonder if the other seminal fluids might be having an epigenetic effect directly on the fertilized egg.

  2. Matt Gruner
    November 15, 2013

    This reminded me of Jean-Jacques Remy’s work on olfactory imprinting in the roundworm C. elegans. He found the worms are more attracted to odors experienced during development and that this enhancement could be inherited for over 40 generations. Others have found that small RNAs are essential for multigenerational inheritance of resistance to viral infections in C. elegans. Fascinating stuff!

  3. David Whitlock
    November 16, 2013

    This is very interesting. Since the fetus can hear sounds in the environment, do sounds associated with maternal stress potentiate stress responses in the infant/child/adult?

    Pretty powerful explanation for the cycle-of-violence, and the importance of breaking that cycle before it can affect the next generation. That means prevention, and especially the prevention of violence against women.

  4. Gerarde Carlton
    November 17, 2013

    This sounds really fascinating. It does seem to be based fairly heavily on naturalistic observation though. Further research should find a way to try and induce emotional reactions to these smells in some way. Correlation does not necessarily mean causation and I can see several confounds in the experiments. It’s definitely worth investigating further, though.

  5. Darold A. Treffert, M.D.
    November 18, 2013

    I have been involved in research on how savants “know things they never learned” (see http://www.savantsyndrome.com) Something I call genetic memory..There is plenty of room on DNA for transfer of huge amounts of “knowledge”, not just instincts. Fascinating ‘grist for the mill’ for my work with genetic memory.

    Darold A. Treffert, M.D.

  6. reader
    November 18, 2013

    I thought additional stress produced higher levels of cortisol, not lower levels.

  7. Leah Jones
    November 18, 2013

    This is absolutely fascinating ! ! ! ! ! I’m not a bibliophile, or a Christian, but could this be a way of explaining “And the sins of the fathers shall be visited unto the children, even to the last generation?” I’ve never thought that to mean punishment of any kind, but rather genetic traits, so that the CHILDREN will have the “ways” of their fathers passed onto them. This amazing article seems to say “yes”.

  8. Chris
    November 18, 2013

    Doesn’t stress increase , not decrease, cortisol levels ?

  9. JBQ
    November 19, 2013

    Just from reading the title, I had a gut feeling this had something to do with the epigenome. Surprising it gets mention in the article but the scientists don’t consider it as a hypothesis. It seems to me there has been a lot of evidence indicating that the epigenome works as an ancestral memory and tweaks hormonal triggers to better adapt to the last few generations’ conditions. Even before this study, I had really been wondering where instinctual fears come from, like those exhibited in domestic cockatiels that had never seen snakes when they encounter something that looks like one. Basically, they will panic seemingly out of nowhere, even if they’ve never seen a living snake in their lives.

  10. Max_B
    November 20, 2013

    Without a published paper to read it’s hard to deduce much from this. Eric Nestler did similar research in 2011 using defeated rodents, compairing the inheritance effect in offspring conceived through IVF to natural conception. He found a big difference, but still did find an inheritance effect in IVF, but more subdued.
    Nestler considered that the IVF harvesting process itself might have preselected immature sperm.
    That an inheritance effect is occurring in these IVF studies looks plausible to me, but there is a wild card option still left. To collect the Sperm in Nestlers experiments the rodents were killed, leaving the door open on a field type effect, that has not yet been ruled out.
    When or even if this paper gets published we might get to know more.

  11. Robert Cook
    November 21, 2013

    This must have profound implications for the ideas of Natural Selection. I understand that Darwin himself became rather sceptical that it was sufficient in itself to explain the speed and apparently directed nature of evolution, and so later returned to looking more closely at Lamark’s ideas of inherited characteristics. These findings would give such speed and directedness to a process that otherwise often seems to be a rather meandering and unconvincing driver of developmental.

  12. Anthony McCarthy
    November 21, 2013

    It’s interesting that the negative reaction to this story in tweets is all about the reported phenomenon whereas I’m rather interested in the immediate assumption that it would necessarily fit into some baseless, unevidenced scenario of natural selection. The fact is that even if the phenomenon can be irrefutably established and a mechanism of its inheritance firmly attached to it, the purported place it would have as an evolutionary adaptation could never be anything but speculative since it is impossible to go back in time and research its presence in varying strength and its effect on reproduction rates. Yet that enormous leap into the unknowable seems to be considered less outrageous than the presentation of a presumably observable phenomenon which could be reproduced.

  13. KT McCann
    November 21, 2013

    My cats exhibited an astounding behavior–my partner brought a snakeskin into the house to show me. It got put down. One by one, as the cats found it, they began behaving as if there were a deadly predator in the house–and universally they began to avoid the floor and walk around the house on top of available furniture, the backs of couches, jumping to tables, etc. Their tails would jerk as if they were preternaturally on edge. Finally after observing this for a few days, we took pity on them and put the snakeskin outside, and life returned to normal! I don’t believe a single one of them ever encountered a snake in real life. Where did the reaction come from?

  14. Mel Tisdale
    November 22, 2013

    The process described in the article involves inheriting a negative experience. Could it be, I wonder, if what is really going on is that all experiences are inherited, both good ones and bad ones. That would be only a small step to inheriting skills, such as spiders web building and infant bird migration to a country that they have never seen before, etc.

    As for any connection with evolution, it would be informative to track whether the increase in neurons in the noses of subsequent generations was maintained as the number of generations not exposed to the supposedly harmful smell increased and the ‘memory’ of the harm became more distant.

  15. Kent
    November 23, 2013

    I am a Bible believer.

    The quote referenced by the other is as below. It is not to the “last generation”

    (Exodus 20:5) – “You shall not worship them or serve them; for I, the Lord your God, am a jealous God, visiting the iniquity of the fathers on the children, on the third and the fourth generations of those who hate Me,”

  16. Seeker
    December 8, 2013
  17. caw
    December 16, 2013

    When you think about what an advantage it is to our species to nurture our children – communicate and teach from experience – it would be remarkable if evolution had NOT found some fairly direct mechanisms to perform this function.

  18. Tim Holt-Wilson
    December 21, 2013

    Here’s a blog post which explains how these effects may have come about. It’s well-written and worth reading it its entirety.
    http://aeon.co/magazine/nature-and-cosmos/why-its-time-to-lay-the-selfish-gene-to-rest/

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