I’m still surprised that the 2011 paper by Nestler et. al. “Paternal Transmission of Stress-Induced Pathologies” hasn’t received more consideration.
Eric Nestler wanted to remove any possible contact by the defeated rodent fathers, with the impregnated female rodent, so used IVF. Comparing the results against defeated rodent fathers who conceived naturally. The offspring never meet their father in all the experiments.
Nestler assumed that if the transmission was really Epigenetic, (through the sperm of the rodent father) there would be no difference between the inheritance effect in IVF offspring, compared to naturally conceived offspring.
However, he found a big difference between the inheritance effect in IVF, compared to natural conception. The problem is he still found an inheritance effect in IVF, just more subdued. Indicating something much more complex is going on.
I find his results perplexing, and I can’t understand why they haven’t been discussed more. If it’s not Epigenetic, then they should find no inheritance effect from the IVF rodent fathers, not a smaller inheritance effect than naturally conceived rodent fathers.
Nestler’s only potential explanation is that the IVF process itself, inadvertently selected immature sperm, that seems reasonable.
However, I dug into the paper, trying to find out if there were any other differences in the way these experiments might have been conducted, beyond the stated ‘IVF’ vs ‘natural conception’ process?
I asked Nestler what happened to the IVF rodent fathers, he replied that at their labs, the IVF-control and IVF-defeated rodent fathers were killed as part of the process to extract sperm from the testes.
Get it…? The rodent father’s were not alive during the course of the IVF experiments (i.e. pregnancy/offspring-development phases). This is not mentioned in the paper, as Nestler can’t see why the fathers being dead or alive during offspring development should make any difference.
However, because of this his experiments are not identical (apart from the IVF vs Natural Conception). ‘IVF’ fathers were already dead, whilst ‘natural conception’ fathers were still alive during the females pregnancy and offspring’s development. This significant difference is not mentioned in the paper, and it needs a bit of exposure in my view, because it keeps the door open on a ‘field type’ effect.
So wouldn’t it be interesting to generally replicate Nestler’s experiment, but this time keeping an additional group of IVF defeated rodent fathers alive during the whole course of the experiment. By using a different technique that would allow sperm extraction without killing the fathers. This would allow us to see if there is a difference in inheritance effect between offspring from dead IVF fathers, as opposed to living IVF fathers?