Tracy Bale, PhD, Professor in Pharmacology and Psychiatry, and Director for the Center for Epigenetic Research in Child Health and Brain Development, talks about research that aims to determine if long-term stress can pass on negative effects to offspring.
What is your focus and area of expertise?
BALE: My area of expertise and background is in neuroscience and endocrinology. I really study the impact of stress in many aspects as it relates to the developing brain, or maturing brain. We do a lot of research on intergenerational transmission of stress or trauma in the environment. For example, how Mom and Dad can pass on effects that alter how their offspring’s brain develops and functions.
Why were you and your colleagues interested in looking at this topic of stress and fertility and then possibly passing on stress to children?
BALE: My lab has been studying the impact of parental stress, especially mom, for well over a decade. Studying mom’s interaction with her environment and its effect on her offspring seems straightforward. About a decade ago, we started thinking about we know less about dad’s role and interaction with his environment. So early life, childhood experiences that dad might have that may impact how his germ cells grow and mature. There’s lots of reasons for the differences between mom and dad and how their germ cells grow, develop and mature that had led to a deficit in this area of understanding. So, we started doing studies about a decade ago trying to understand the influence of the environment on dad’s germ cells and then whether those changes actually meant anything. We can always, as scientists, define things that are different, but then we want to know do those differences have meaning? As neuroscientists, we’re especially interested in the child’s brain. So, if dad’s experience and his environment albeit stress, trauma, early childhood adverse events, those sorts of interactions, do they have lasting effects on his germ cells? You can think about dad coming home from military service and he experienced a traumatic brain injury or PTSD from his injuries. That might be a chronic situation that affects his germ cells. But what about effects that happened in his childhood? Do those also place lasting effects? So, we study mice, but all of the research in my lab that we learn from the mice we then take into humans. We have both mouse data and human data in this area.
Talk to me about what you found or how did you go about studying this?
BALE: Over the last decade, we’ve been looking at the effects of exposing mice to chronic stress. That’s where we can take a male mouse and expose him to different things in his environment. Mice have a very controlled environment so it’s really easy to stress them. Mice are also creatures of habit and comfort, so it’s very easy to make them respond to stress. We just do something very mild to their environment every day around the same time of day so that they’re reacting in a way that is out of their circadian rhythm. That allows them to produce glucocorticoids, which are the same for humans as they are for mice, out of circadian rhythm and that can interact with all kinds of cells in their body. Our question was, do those glucocorticoids interact with cells along the reproductive tract and does that also relay a difference in signal in dad’s sperm. Ultimately, sperm is going to reach the egg and we want to know about that signal. So, we set out to do a chronic stress experience on dad and then look at the timing after that stress resolved. Did he pass on effect to his offspring? A model that we developed about 10 years ago showed that, in fact, his offspring did. They had dramatic changes in the maturation rate of their brain. It wasn’t like we were modeling autism or schizophrenia, but really this is about the rate at which your brain develops. Certain things must happen at certain times. If you speed up development or slow development, you’re changing the fine tuning of those processes. So, you’re not modeling the disease, what you’re modeling is an additional risk. You already have genetics that put you at risk for a given to your environment, now you have that insult of your environment and, you’re more likely then to present with a given disorder.
How do you take what you studied in the lab and bring it to people?
BALE: All of our mouse models in the lab have a human component. So, from the University of Pennsylvania, when I was faculty there, we recruited men. So young, normative subjects just to ask this question about if we could look at and measure the stress in their environments over final exams. Could we detect changes in their sperm compared to their previous month or their next month. We collected samples each month and found some amazing differences and that’s a study we just submitted for publication as well in the human subjects. Some of that data is in our current publication. So yes, there are, in fact, detectable differences and we know from our mouse studies that what those differences are have meaning for how that child’s brain will develop.
What are the implications of the study? If you see that there are those changes, what does that suggest to people?
BALE: What that suggests is from what we do in the fertility clinic, from understanding these attached signals, or extracellular vesicles that interact with that sperm, they wash away not knowing what the role is. So, everything from understanding normal fertility measures to trying to understand men who may have been exposed, to extreme stressors or traumas, etc. Once we better understand what those biomarkers are and understand what they do, then we can better understand who we might want to assay in terms of humans. For instance, a man coming home from military service. He’s at that age where he might be having children. Are there things that we can assess in his sperm easily and then ask, are there ways that we might want to intervene or not? So, we need to understand first what those markers do. That’s where we are right now is the biology of what do these changes mean and are those changes just different because we as a culture celebrate diversity or are those differences a risk? And if they are a risk, would we want to intervene?
So, it’s not affecting the fertility, it’s affecting how the children’s brain would develop because the father was under stress?
BALE: Exactly right. We do have evidence that stress increases fecundity. We have lots of examples of this we can go through. But when you’re under extreme stress, once that stress is resolved, fertility tends to go up. So, fertility isn’t really the issue with these extracellular vesicles that we’ve been looking at, it’s actually the effect it has on the rate of the offspring’s development. You might imagine, evolutionarily, if there is pervasive stress in an environment, like we have right now, that evolutionarily it might make sense to sort of speed up the rates of development to crank out more children because if the environment is stressful, what does that mean about survival? So, we go back to our roots. That is really not at the level of fertility, but more about the rates of development and what consequence that might have for the brain.
From a practical standpoint, especially if they’re men who are thinking about becoming fathers in the next couple of months, what can people do?
BALE: We can’t say at this time because we can only assess things that there are differences. I can’t say yet that those differences are necessarily bad. In fact, there’s lots of evidence with the studies on grit that many times under certain stressful conditions we actually rise above. So, we cannot say that these differences are necessarily bad. They may, in fact, be more in terms of survivability or best fit for an environment. All we know at this time is that they are, in fact, different.
Do you have any suggestions or recommendations in reducing stress?
BALE: Well, chronic stress is never great for anybody. So, the recommendations that I always make, as a PhD not an MD, for both moms and dads, is that finding healthy ways to deal with our stress, which is huge right now. Healthy ways to get some exercise, eat healthier, avoid things such as drugs of abuse or ways in which that might not be healthy for us or our children is the best advice that we can give. Find ways to cope.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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