After the replication crisis and "Why Most Published Research Findings Are False," I am very sceptical of statistical findings like this with a poorly/not understood mechanism.
But the RNA theory at least sounds possible to layperson.
> I am very sceptical of statistical findings like this with a poorly/not understood mechanism.
And you’re right to be (in fact, this is exactly the same instinct researchers get). We’ll have to wait until the actual research article is published before we can assess the quality of their evidence. But in their defence, they performed a so-called functional verification by knocking out the suspect gene (MIR206) in mice and looking for phenotypic changes. It is relatively straightforward to perform this in such a way that you get statistically robust results. And it’s also straightforward to replicate independently, which will happen in due course.
As somebody who’s working on a highly related topic, I’m thrilled to see the research explained so well here. But unfortunately I am unable to assess the quality of the findings because the researchers have decided to buck convention and went to the press before publishing their scientific manuscript.
And this immediately sets off alarm bells: Unfortunately experience shows that when researchers skip the “due process” of peer evaluation and go directly to the press they usually oversell their findings. I hope this isn’t the case here, and the findings hold up under scrutiny.
My own experience is that working with sperm RNA is a b*tch because of high stochastic noise. It’s basically impossible to get any clear signal from a whole-transcriptome assay. I’m therefore quite interested in their quantification.
Maybe. It’s really too early to say. Even assuming the mechanism described here is correct, there’s a difference between mice and humans, and there’s a difference between merely being stressed and a systemic stress response that would affect the sperm production (which, by the way, doesn’t occur just during sex but before).
And, finally, the effect on the offspring is completely unclear. One of the effects, which was reported here, is that offspring is less stressed (why? how? we don’t know; that’s a major missing puzzle piece). But systemic stress has quite a few, and partially drastic, effects — increasing expression of a particular microRNA is just one of many consequences. It also generally negatively affects semen quality (e.g. [1]), which doesn’t fare well for procreation.
And even just that particular microRNA in question, MiR-206, is tentatively implicated in multiple disease predispositions. You might make your children slightly less stressed. Or you might make it slightly more (or less) likely for them to acquire muscular dystrophy or schizophrenia.
>and there’s a difference between merely being stressed and a systemic stress response that would affect the sperm production (which, by the way, doesn’t occur just during sex but before).
According to the way the research was described, this mechanism acts outside of the genetic code, so it isn’t a matter of when sperm is produced. These particles can latch on to the gamete long after the gamete is produced. For example they can be present along the lining or interstitial fluids in the epididymis, where sperm passes through from the testes during reproduction.
> They could equally well be attached to sperm just before sexual intercourse. Ms Chan therefore concentrated her attentions on part of the male genital tract called the epididymis. This is where sperm mature. Cells lining the epididymis constantly discharge small, fluid-filled, membrane-bound bubbles called vesicles. When Ms Chan, working with mice, looked in detail at these vesicles, she found that they contained lots of micro-RNAs.
So, if you have unprotected sex with a women who recently was or will be impregnated by another man, you can still pass your microRNA and affect the child?
Don't know anything about RNA, but I wonder if some kind of small virus could be used to test the micro RNA transport hypothesis. Googling "micro RNA virus", first link is https://www.ncbi.nlm.nih.gov/pubmed/21431678 . The paper seems promising, since 2004, more than 200 microRNAs (miRNAs) have been discovered in double-stranded DNA viruses, mainly herpesviruses and polyomaviruses.This chapter aims to summarize our current knowledge of viral miRNAs, their targets and function, and the challenges lying ahead to decipher their role in viral biology.
Using microRNA virus to test the sperm transport mechanism seems to be a good idea.
Glooging for "microRNA virus sperm transport" suggest the link: Intercellular Transport of MicroRNAs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580056/), This review brings into focus what is currently known and outstanding in a novel field of study with applicability to cardiovascular disease.
So, perhaps sperm transport of microRNA could be tested using some RNAvirus to produce cardiovascular desease.
So you’re suggesting injecting viral miRNA into the epididymis of parental mice and checking for symptoms of viral infection in the offspring? This won’t work because (a) the miRNA isn’t the whole virus, it probably won’t have a clearly discernible phenotype; and (b) the mechanism suggested here relies on specific vesicles. Export of small RNAs into vesicles isn’t an automatic process, it requires active targeting of the RNA inside the cells for export (RNAs essentially need to carry a “luggage tag” that directs the cell machinery to envelope it with a membrane and send it out).
Still, your fundamental idea has some merits. A more promising experiment would forego viral RNA and instead mutate the specific miRNA-206 in mice to carry a specific signature. Sequencing the resulting embryo in early development could show whether the mutated miRNA was taken up. I say “could” because there are fairly big caveat: miRNAs are short-lived (unless they are actively regenerated) and the concentrations may be too low to pick up a signal.
The experiment you suggest seems promising. As a math teacher, I don't know about this field. But to suggest experiments that "could" prove or support and hypothesis is a good way to advance science. Thanks for our suggestions. As a Ph.D. math teacher I don't know about this field.
There's no mention of IVF/in-vitro-fertilization techniques and whether male micro-RNA can survive that process. There apparently are side effects of IVF and I wonder whether they could be due to degradation of male RNA transport.
If you do ICSI with sperm taken directly from the testis, which is quite common, then the sperm never travel through the epididymis and therefore are not loaded with the microRNAs. So yes, you would certainly have removed the (is life good or shitty) signal that the sperm normally would carry with them. The Rando lab at UMass does a lot of this kind of research if you want to go down the rabbit hole...https://umassmed.edu/randolab/
It’s not mentioned because it hasn’t been studied yet. That said, side-effects from IVF can be explained much easier, no need to invoke degrading sperm RNA (which is almost certainly not required for healthy fertilisation, and rather a side-effect): IVF is a fairly disruptive and stressful procedure for cells: Among other things, it requires processing cells outside of their natural protective environment. Even though it’s a routine procedure, there’s a high failure rate (which is why multiple oocytes are collected and fertilised, and subsequently the best embryo is picked for implantation).
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[ 1.1 ms ] story [ 72.9 ms ] threadBut the RNA theory at least sounds possible to layperson.
And you’re right to be (in fact, this is exactly the same instinct researchers get). We’ll have to wait until the actual research article is published before we can assess the quality of their evidence. But in their defence, they performed a so-called functional verification by knocking out the suspect gene (MIR206) in mice and looking for phenotypic changes. It is relatively straightforward to perform this in such a way that you get statistically robust results. And it’s also straightforward to replicate independently, which will happen in due course.
And this immediately sets off alarm bells: Unfortunately experience shows that when researchers skip the “due process” of peer evaluation and go directly to the press they usually oversell their findings. I hope this isn’t the case here, and the findings hold up under scrutiny.
My own experience is that working with sperm RNA is a b*tch because of high stochastic noise. It’s basically impossible to get any clear signal from a whole-transcriptome assay. I’m therefore quite interested in their quantification.
And, finally, the effect on the offspring is completely unclear. One of the effects, which was reported here, is that offspring is less stressed (why? how? we don’t know; that’s a major missing puzzle piece). But systemic stress has quite a few, and partially drastic, effects — increasing expression of a particular microRNA is just one of many consequences. It also generally negatively affects semen quality (e.g. [1]), which doesn’t fare well for procreation.
And even just that particular microRNA in question, MiR-206, is tentatively implicated in multiple disease predispositions. You might make your children slightly less stressed. Or you might make it slightly more (or less) likely for them to acquire muscular dystrophy or schizophrenia.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382866/
According to the way the research was described, this mechanism acts outside of the genetic code, so it isn’t a matter of when sperm is produced. These particles can latch on to the gamete long after the gamete is produced. For example they can be present along the lining or interstitial fluids in the epididymis, where sperm passes through from the testes during reproduction.
However, the transport of micro RNAs on sperm is a pretty cool mechanism - hope it is correct!
So, if you have unprotected sex with a women who recently was or will be impregnated by another man, you can still pass your microRNA and affect the child?
Using microRNA virus to test the sperm transport mechanism seems to be a good idea. Glooging for "microRNA virus sperm transport" suggest the link: Intercellular Transport of MicroRNAs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580056/), This review brings into focus what is currently known and outstanding in a novel field of study with applicability to cardiovascular disease.
So, perhaps sperm transport of microRNA could be tested using some RNAvirus to produce cardiovascular desease.
Still, your fundamental idea has some merits. A more promising experiment would forego viral RNA and instead mutate the specific miRNA-206 in mice to carry a specific signature. Sequencing the resulting embryo in early development could show whether the mutated miRNA was taken up. I say “could” because there are fairly big caveat: miRNAs are short-lived (unless they are actively regenerated) and the concentrations may be too low to pick up a signal.