Inheriting Our Father's Experiences

Last night I was out with one of my favorite characters from Dalhousie, and I say “character” because that’s exactly what she is. Rahia is creative, funny, outspoken, and has a great scientific mind. Rahia is also currently a PhD student at Columbia University in New York (http://champagnelab.psych.columbia.edu/rahia.html). 

Over (great) beer at this off-the-beaten-path bar, Downtown Johnny Brown’s, Rahia was telling me about her research on the transmission of experiences from fathers, via epigenetic mechanisms to the offspring (see previous post: /mandywintink/2012/11/epigenetics-stress-science-review-part-1.html). That in itself is interesting but what was of particular interest -- both to me that night and to Rahia for the past year as she slaved away in the lab -- was whether or not the mothers could regulate the expression of the fathers experiences in utero such that it would change the fate of the offspring. Indeed, Rahia’s data suggest that moms can!  As Rahia put it, it’s like the mom looks at the dad and say “You sucks” and then compensates for that dad inadequacies!

One example of this is when moms may need to overcompensate is when the dad are food restricted and therefore not as healthy as one would like. When the female mates with the food-restricted male she ends up gaining significantly more weight during pregnancy and nursing the young more after birth, thereby compensating for the nutritional deficits of the dad. There are also corresponding changes in the brains of the mom, such as changes in the hypothalamus, an area of the brain regulating several hormones and their dependent behaviours of feeding and stress. This research is interesting indeed: Moms can compensate for the inadequacies of the dads. Like women didn’t already know that, right!?  ;)

But what if the mom doesn’t know that the father has inadequacies? That was the question Rahia posed wondering if moms would fail to compensate for those inadequacies, for example during in vitro fertilization when mating doesn’t actually happen the same way. Rahia tested this by mating females with an “adequate” male that were castrated (so it would not actually impregnate the female), then knocked the female unconscious and knocked her up with the sperm of another male that was food-restricted (a male that was effectively “inadequate”). Btw, this was all done in laboratory rats!  ;)

Interestingly, astonishingly, and super coolly, the females failed to compensate for the inadequacies of the biological dad! They didn’t gain weight or nurse the young more and the result were offspring that had several memory and attentional problems!

This line of research is incredibly interesting from a scientific perspective and I look forward to hearing about how Rahia’s studies evolve. But this work also fits into a greater field of study where several researchers are investigating these transgenerational epigenetic effects, i.e., the effects of experiences that are encoded (epigenetically) within the genome and passed on to future generations. I have written about these before, with respect to inherited stress and maternal care (see /mandywintink/2012/11/epigenetics-stress-science-review-part-1.html) Today, at the Society for Neuroscience Annual Meeting, scientist Tracy Bale was speaking about this some transgenerational effects she observed, particularly in male laboratory animals. However, we can see justification for this field of research from some historical events, such as the post-WWII calorie-restricted legislation in Holland that forced people, including pregnant women, to eat no more than 400 - 800 calories only a day. That is ridiculously low for those who don’t know. To compare, look up what a Cafe Mocha has and your jaw will drop. The Holland food-restriction, along with several other times of famines, have been investigated and revealed behavioural effects (like anxiety and chronic disease susceptibility) that can be detected in the grand children of people who endured these times. 

In the lab, this has been investigated again with rats under several different circumstances. For example, exposing a father to repeated social defeat results in altered social behaviour in the offspring (think the McFly family from the Back to the Future series). High fat diets in dads also results in dysregulation of glucose and several metabolic processes related to obesity as well as epigenetic changes in the liver. Chronic stress is another model, one that Bale uses in her laboratory. In the process she and her student have revealed some some interesting findings. For example, when dads are exposed to chronic stress (as adults and during puberty) they produced offspring that developed a maladaptive stress system reflected by a poorly functioning hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a neural system that regulates the stress response, a response that is need for proper coping strategies. Essentially what Bale and her students have found is that the offspring of males who were chronically stressed themselves, were less equipped to deal with stress. 

Bale’s lab has begun to isolate some of the contributors to this poorly functioning stress system including changes in microRNA, a component of epigenetic changes. They identified 9 microRNAs that were expressed (or upregulated) in the offspring of dads that experienced chronic stress. In a creative set of follow-up experiments, Bale’s lab determined that these microRNA were causing some of the offsprings problems by  simply injecting the microRNA right into a developing zygote of non-stressed dads, effectively simulating an experience of paternal stress. The results were as predicted: similar dysfunctional changes in the stress system rendering the offspring less equipped to deal with stress.

Although much of this review was about the negative effects of transgenerational experiences, in fact there are adaptive circumstances that put the offspring in a better predicament, resulting in a more resilient start. Bale ended her talk by suggesting that whether or not one ends up in a resilient or a risky situation after birth is a matter of coping, i.e., how we respond to changes in the environment. Rahia would likely argue that part of these coping mechanisms begin long before the offspring are born and consist of biological and behavioural strategies used by the mom to compensate. 

Complicated and exciting work indeed! For me, this was interesting largely because of the hypotheses and how the researchers, like Rahia, tested them. But when I take a step back and wonder about what this all means I can’t help but think about that common rationale that floats around for why men are thought to be more promiscuous than women. You know the one that says males are biologically predisposed to spread their seeds where as women are biological predisposed to nurture? All of this data makes me wonder about the truth of that whether laboratory animal or human men. I wonder about those men who chose to invest in the seeds they have planted and who do a really great job at it. I think of many of my friends where the men are stay-at-home fathers. I wonder, what sort of things are the women doing to compensate for these really good men? Perhaps, if those men are offering a great nurturing experience post-natally, and the women can detect this - just like they can detect malnourished, chronically stressed, or socially defeated males - would those moms then go on to divert their resources to something else instead of compensating for the dad’s inadequacies? What if, instead, moms could focus on nurturing high-level behaviours of the offspring. It kind of reminds me of Maslow’s Hierachy of Needs. It also kind of makes me want to be back in the lab studying this stuff myself. But alas... I cannot discriminate against all of the wonderful fields of research out there!