Sex Cells and Inherited Trauma – De-Natured
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Sex Cells and Inherited Trauma – De-Natured


On Nature League, we spend the third week
of each month exploring a current trending article from the peer-reviewed literature. Scientific information isn’t just for scientists-
it’s for everyone! It just requires a bit of a break down. [CHEERY INTRO MUSIC] For this month’s De-Natured segment, we’re
going to look at an article released in May 2018 in the journal Translational Psychiatry. In this month’s Lesson Plan, we talked about
the different ways that organisms make more of themselves. We also discussed the biggest biological advantage
of sexual reproduction, which is increasing genetic diversity by combining multiple sex
cells. But it turns out that sex cells aren’t the
only things being passed onto the next generation. We’ve long understood that certain individual
traits we have come from the DNA inside of eggs and sperm given to us from our parents. But what about something…not so great? What about trauma? This paper is entitled, “Reduced levels
of miRNAs 449 and 34 in /sperm of mice and men/ exposed to early life stress” and yes,
that is also the title of a play I would definitely pay to see. Theatre references aside, the title contains
some concepts we should dig into. Particularly, miRNA and what we know about
their reduction in levels. So here’s what’s already known. Being exposed to severe stress during childhood
can absolutely have negative health effects later in life. For example, studies have shown that adults
who report having experienced more childhood trauma are more likely to experience depression
and struggle with suicidal thoughts and tendencies. But here’s the thing- the trauma doesn’t
stop at the adult who experienced it. Scientists have also noticed that children
of parents who experienced trauma as kids are at a higher risk of developing psychiatric
disorders. So how does this trauma persist across generations? Several mechanisms have come to light, but
the one with the most current scientific support has to do with small RNA in sperm. Ribonucleic acid, or RNA, is single-stranded
genetic material. One of its most famous jobs is delivering
the genetic code from inside of the cell’s nucleus to a cell’s ribosome, where that
same code is eventually translated into all of the proteins we know in life on Earth. I mean, no big deal guys, just, y’know,
making the building blocks of life over here. And as if that wasn’t a big enough job,
there are actually all /kinds/ of RNA that do a ton of different things. It turns out that sperm cells contain several
types of RNA…and because it’s sperm we’re talking about, these RNA have the potential
to affect the development of the embryo formed between that sperm and an egg. Scientists have used mice to figure out ways
that trauma can persist across generations, and two separate studies have concluded that
it is specifically microRNA, abbreviated as miRNA, that might play the largest role. But mice are mice, and although we have many
similarities, the way that stress and microRNAs are related in mice might be different than
in humans. So, in this brand new paper, scientists investigated
how trauma early in life can affect the levels of microRNA in the sperm of…you guessed
it. Mice /and/ men. To address this phenomena in humans, the scientists
took a sample of adult men and conducted an observational study. In this kind of research, the experimenters
don’t actually change anything that happens to the subjects- they simply ask them about
previous experiences and measure some kind of response variable at the present time. In this scenario, they measured their extent
of childhood trauma by using something called the adverse child experiences, or ACE, survey. This questionnaire has the participating adult
answer 10 yes or no questions regarding their experiences at home until the age of 18. Half of the questions are about the experiences
of the participant themselves, and the other half have to do with other family members. This is an observational data set- all of
the things already happened, and the scientists didn’t cause any of them to occur in a lab
environment. But, observational studies do still measure
some kind of response. For this study, the men who took the ACE survey
also provided a sample of semen, and that semen was filtered down to mature sperm that
provided some data. Demographic, behavioral, and general sperm
characteristics were recorded as response variables, and then the researchers compared
these results to the ACE survey scores that measured childhood trauma experience. Of the 28 men included in the study, half
scored between 0 and 1 on the ACE survey and were labeled as the low ACE group. “Low” in this case means they had experienced
a low amount of childhood trauma. 7 men scored between 2 and 4, and the remaining
7 who scored more than 4 were labeled as the high ACE group, meaning that they had experience
a high amount of childhood trauma. Since this paper is of mice and men, and our
ability to ask mice survey questions isn’t /quite/ developed, the researchers exposed
the study mice to early life stress by randomly shuffling the individuals into different enclosures
twice a week for 7 weeks. Nothing life threatening or painful, but still…it
definitely sucks to get a new apartment and roommates every few days, and this level of
stress was enough for the researchers to compare experiment groups. Since previous work had shown that microRNA
could be one of the ways trauma gets passed on to other generations, the scientists looked
at the expression of microRNA in the sperm from the low ACE group and compared it to
the high ACE group. Out of the hundreds of microRNAs detected
in the human sperm samples, the team found that microRNAs in a specific family called
miR-34 and miR-449 had the most significant differences in expression between the low
childhood trauma and high childhood trauma groups. This was an interesting find on its own, as
these specific families of microRNA have been shown in some studies to affect things like
brain development and mature sperm development, as well as adult brain stress regulation. Once they knew to check out the 34 and 449
families of microRNAs, they measured the expression levels of these microRNAs in all of the study
participants. So what did they find? For most of the demographic, behavioral, and
general sperm characteristics, the team didn’t find clinically significant differences between
the low, medium, and high ACE groups. However, they did find a statistically significant
inverse correlation between the levels of microRNAs 34 and 449 and ACE scores. Finding an inverse correlation just means
that a pattern is found between two variables, and when one goes up, the other goes down
(or vice versa). So in this situation, it means they found
significantly /lower/ levels of the microRNAs in /higher/ ACE score groups- those were the
adult men who had experienced more early life trauma. Statistical significance aside, these differences
were /really/ noticeable. In fact, the paper reports that many of the
men in the high childhood trauma group had sperm with microRNA 34 and 449 levels /300-fold
lower/ than many of the low childhood trauma group men. It’s one thing to find a statistically significant
difference between two groups, but the scientists had to make sure that the differences were
associated with early age trauma instead of something else. Even though data in other studies have shown
that microRNA levels in sperm can be affected by smoking and obesity, this group of researchers
/didn’t/ find a statistically significant difference between these microRNA levels of
smokers vs non-smokers or high vs low body mass index scores. They also didn’t find any significant differences
between microRNA expression when they looked at variables like drug and alcohol use, sperm
count, and sperm motility. By ruling out associations with other variables,
the researchers were able to conclude that childhood trauma, as measured by ACE score,
is associated with lower levels of certain sperm microRNAs. The researchers found the same statistically
significant differences in these sperm microRNA levels in mice when they compared the control
group with the group that was exposed to the roommate shuffling stress we talked about
earlier. Since mice can reproduce and mature much faster
than humans, the researchers were able to do some additional follow-up on the offspring
of the stressed male mice. They found that in mice, microRNA 34c and
449a levels were also reduced in the embryos resulting from a stressed male mating with
a control female. The amazing thing, though, is what they found
next. Not only did the stressed male parent mate
and produce embryos that had those lowered levels of microRNAs, but the male embryos
that grew into adult mice /also/ had sperm with reduced levels of microRNAs. That’s right- the changes associated with
trauma had actually been passed on across generations. This paper has received quite a bit of attention
in both scientific circles and public media outlets. Here are some reasons why I think this study
is creating such a buzz. The world of genetics is currently undergoing
major renovations. Whereas developmental biologists used to pose
the question “nature vs nurture”, we’re now figuring out that the answer is a hard
“nature AND nurture”. There’s a wave of epigenetic research happening
right now in almost all spheres of science. Epigenetics refers to inherited changes in
gene expression that don’t affect the actual genetic code, and this study is just one of
the many exploring this trending topic. And when it comes to psychiatry, epigenetics
isn’t a trendy topic just because it’s interesting- it also has major implications
for understanding how trauma affects ourselves and others. We’ve discussed in other De-Natured episodes
that being first is definitely one way to make waves in science, and this study is no
exception. One reason the results are getting so much
attention is because this is the first time a research team has identified specific changes
in human sperm microRNA levels in association with early life trauma. And that association means that the specific
microRNA 34 and 449 molecules could eventually be used in screening individuals for trauma. This could be a big step forward in clinical
situations if a microRNA screening was used in addition to the ACE questionnaire. Due to the nature of the questions on the
ACE survey, it’s possible that some patients don’t respond accurately, or might experience
distress while sifting through painful past experiences. So, these microRNA markers could be used as
a complement to the ACE surveys in clinical settings, and that could be a big deal for
the mental health profession moving forward. Any observational study runs into problems
when it comes to establishing causation. All we can really accurately speak of is correlation-
basically, the fact that two variables were seen to have a relationship. My biggest problems with this study have more
to do with the sampling design than with the fact that it’s observational, and there
are several that jumped out at me. First of all, the 28 human subjects were voluntary
participants, which means it’s possible that we’re getting a biased sample. For all we know, low microRNA 34 levels cause
men to love being part of research trials, so we just got a group of men with a confounding
variable we didn’t know about. Additionally, the 28 men were all Caucasian,
so we can’t apply these results to the human population as a whole. And then there’s the sample size. 28 semen samples. The researchers mention that they were aiming
for a sample size of 35 in order to have more statistical power, but they halted recruitment
at 28 due to low clinic volume. When studies have a smaller than optimal sample
size, there is always a possibility that the results they observe are due to chance alone. Throughout the discussion section, the authors
do a great job of recognizing these downfalls in methodology, and they suggest ways that
the study can be expanded and improved in the future. Regardless of these methodological improvement
points, this study is an amazing example of a first step toward understanding the physical
mechanism underlying the inheritance of trauma. And figuring out the way our actions can affect
those who aren’t even born yet is definitely worth the time and effort it takes to improve
on current work. Thanks for watching this episode of De-Natured
here on Nature League. Nature League is a Complexly production, and
if you want to learn more about how trauma can be inherited, check out this episode from
our sister channel, SciShow Psych.

17 thoughts on “Sex Cells and Inherited Trauma – De-Natured

  1. Has there ever been a study done on children of veterans, conceived during the soldier's deployments, or shortly after..?

  2. Thank you, this was really interesting 🙂 Also a good example of how small studies don't have to be unimportant!

  3. How to even deal with selection bias?
    Do you, like, offer secretly the same study in several tiers?
    "voluntarily" (no compensation)
    "with incentive" (i.e. monetary reward or something, possibly several variations"
    "targeted" (i.e. find people who, in this case, you already know have high/low childhood drama and ask them to participate?)
    "forced" (O.o)
    ?
    And then look for statistical differences between those classes?
    I'm guessing as the sample size approaches huge numbers, concerns with that might go down, but it's still a weird issue. I mean, it's an important and valid issue, but "the fix", at least as far as I can tell, is pretty hard to employ.

    To deal with low sample sizes, is a permutation-based analysis reasonable? I'm not sure if it actually makes sense in this case. (Also I haven't read the paper, maybe they already did that regardless) – I'm talking about what is explained here: https://youtu.be/bPZFQ6i759g

    EDIT: Or is that permutation thing only useful for processes in time?

  4. 9:29 but i thought race is a social construct, are you telling me that there exist significant genetic differences between ethnic groups? that's ridiculous

  5. So erm … they jerked off mice?

    There are whole illnesses that are inherited that are "gained" during the life of the parents like Borderline Personality Disorder. So is this the real reason for epigenetics? And how about females? The egg cells are developed before birth so does those traits jump one generation? So many questions! We need more science and research!

  6. Fascinating, I've checked in (here and there) on this kind of research for almost 20 years, now.

    It's too bad the study is so limited by sample size.

    In the category of being an easy mark, this video and study supports my long preexisting feeling/belief/leaning toward nature+nature vs either-or.

  7. I am curious where the researchers were located with an all – caucasian test group? An excellent study though! Says a lot for adaptation. Thanks for the knowledge and the breakdown!

  8. Epigenetics is mind blowing. If it wasn't for you guys I wouldn't even know it is a thing.

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