Heat Stress Part 1 with Dr. Marcus Kehrli

This episode explores the groundbreaking research on the long-term and multi-generational impacts of heat stress on dairy cows, focusing on epigenetic changes and their economic implications. Dr. Marcus Kehrli shares insights into how heat stress affects gene expression, fetal development, and future productivity, emphasizing the importance of mitigation strategies.

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Transcript

Chris Radke (01:24)
Hello and welcome to AK Podcasts where we explore science and nutrition behind livestock care management with the best and the brightest in the business. I'm your host, Chris Radke, part of the sales department here at Agri-King. And with me today is the director of field services and a member of the sales management team, Mr. Mike Donaldson. Mike, how you doing buddy?

Mike Donaldson (01:42)
Outstanding, Chris, good to be with you.

Chris Radke (01:44)
Yeah, it's a time, good time. Hey, Mike, who's with us again? And what are we talking about today?

Mike Donaldson (01:50)
But with us today, Dr. Marcus Kehrli is going to review some of the relatively newer findings about the long-term impacts of heat stress on dairy cows. Today's message is going to emphasize why we should be focused on doing all we can to minimize these effects, along with some thoughts on how we can help mitigate some of heat stress' challenges from a nutritional standpoint. When it comes to adding fans, sprinklers, things like that...

There are incredible resources already available. So we are not going to go into that part of combating heat stress other than to acknowledge it's very important. So Dr. Kehrli is now a member of our elite three-time guest club on the AK Podcast. We're looking into a system of pins or something to denote that. so a lot of our audience is already familiar with you. For those who may be meeting you for the first time, Marcus, please give us a

brief rundown on your life and accomplishments.

Dr. Marcus Kehrli (02:53)
Well, good morning and thank you, Mike and Chris. ⁓ boy, you know, a three-peat, ⁓ usually in the sports world, that's quite an accomplishment, but, ⁓ we'll leave that up to the audience to decide after the Podcast, whether in the Podcast world, a three-peat is, ⁓ is, is meritorious. ⁓ Mike, I'm, I'm a farm kid from Northeast Iowa We grew up on a, diversified livestock and crop production farm back in the sixties and seventies.

Mike Donaldson (02:59)
you

Ha

Dr. Marcus Kehrli (03:21)
I've always had an interest in dairy and hog production, because that's part of what we did on the farm. But ⁓ after going off to college and earning my bacteriology and dairy science undergraduate degrees from Iowa State, I went on to earn my DVM degree. And after that, I took a job at the USDA's National Animal Disease Center here in Ames, where my research focused on transition cow immunology and health. Along the way, I earned a PhD in immunobiology while working on that topic.

And after 16 years of that work, I took a job with the pharmaceutical industry for five years where I did a lot of research on drug discovery for unmet veterinary medical needs in livestock before I eventually returned to the USDA again. And while back there, I led a team of 13 to 15 world-class scientists whose research focused on bacterial, viral, and prion diseases of livestock and wildlife.

I did that for about 10 years before I became the director at the National Animal Disease Center for nearly eight more years. So after 40 years of animal health research in various capacities, I decided it was time to hang up my cleats and I retired. So in the interest of full disclosure, after I retired, I was invited to serve on the Agri-King Board of Directors, which I've enjoyed doing since July of 2021.

Mike Donaldson (04:44)
And I will add, we are extremely appreciative of you being on our board of directors, Marcus. I think we've got, we've got kind of a unique situation at Agri-King. Our board of directors don't just get together for dinner and drinks periodically. These people work very hard to help us be a better company. And we appreciate that. But to today's topic, recently, and by that, I mean the last year or two, heat stress has been revealed to be a much further reaching problem.

than it was previously addressed. I'd like to have you explain some of the what, where, when, and why that this new information is revealing.

Dr. Marcus Kehrli (05:25)
Well, Mike, you're exactly right about that. This is fairly new information, although it always takes years for it to come to fruition. We've learned a great deal in these last couple of years on hidden costs of heat stress on livestock. So in this Podcast ⁓ that we had a while back on mycotoxins, you asked me a question about whether consumption of mycotoxins would exacerbate or add to the impact of heat stress on cattle.

While there's no doubt in my mind that mycotoxin consumption will further aggravate the heat stress effects on cattle, ⁓ I felt it deserved its own focus because it's a pretty big topic. ⁓ And I also think the transition cows are particularly vulnerable to the combined effects of heat stress and mycotoxins because they're already dealing with a lot of energy and protein demands with the end of pregnancy and the onset of lactation.

I think they're doubly vulnerable to heat stress. And that is the link to what we're going to talk about today, because that was the focus of a body of research ⁓ that is really quite interesting. In fact, I'm going to say right up front that for a science geek like me, what scientists have found about the multi-generational effects of heat stress on these late gestation cows, it just blew my mind. It knocked my socks off because I would have never ⁓ predicted this.

based on my knowledge of genetics. More importantly for dairy farmers, these findings ought to really drive home the economic importance of heat stress mitigation on their farm. know, the dairy industry, is known for well over a century that heat stress hurts cows, which in turn hurts the bottom line on milk checks. So there's various estimates of what heat stress costs the US dairy industry. They range anywhere from one and a half to two and a half billion dollars.

You know, those are always numbers that you, they're, they're a little better numbers than just picking a number out of thin air, but ⁓ it's obviously a big impact. And globally heat stress is a much bigger problem than just here in the U S. So just to simplify it, heat stress for a cow happens when the combination of temperature and humidity rise to a point where that cow is no longer comfortable and she'll begin to sweat, breathe faster. She may start salivating when it gets bad enough. They seek shade. They, ⁓

We'll seek out water. need lots of water and heat stress affects both sexes as well as dairy and beef cattle. So while much of what I'm going to visit you with us about today is focused on the dairy cow, it's a broader topic than just that. And heat stress is really a problem when cattle are overcrowded and when they're pregnant. So the focus has been, as I said, on the last several weeks of pregnancy. So

I don't think there's anything too earth shattering, Mike, about what I just said, but a little over, well, almost a year ago, one of Agri-King's regional managers reached out to me and asked some questions about research he'd heard about that said heat stress in the last couple of months of pregnancy, in addition to what it does to that cow, can actually negatively impact the productivity and the productive lifespan of the next two generations of calves that are born to that cow.

So as I looked into it more, became apparent to me that we really need to pay attention to keeping your dry cows and transition cows cool. So this new understanding has shown us that heat stress impacts fetal development and the effects on that fetus do indeed extend transgenerationally to the subsequent offspring of even that fetus itself. So both the F1 and F2 generations of that pregnant cow.

Now we've known that calves from heat stress cows would on average have reduced birth weights, impaired immunity and lower lifetime productivity. But now we know that these effects involve epigenetic modifications of their genes while that fetus is still in the uterus.

Mike Donaldson (09:30)
Okay, and not even 10 minutes into the Podcast, we've got to stop for vocabulary lesson. So what in the world is meant by epigenetics? That seems like a, is at least a new term to me, and I have no idea what that actually is talking about.

Dr. Marcus Kehrli (09:41)
.

Well, Mike, that not too surprising to me because even when I was in college, epigenetics was not a term I remember hearing about in any of my genetics or animal breeding classes. And I don't think I had fallen asleep. It's not that the term didn't exist back then, but in the genetics world, it was used to describe a whole lot of things that seemed to be inheritable, but no one really knew exactly how it worked. But since some scientific advances,

Chris Radke (10:01)
Ahem.

Mike Donaldson (10:01)
Yeah

Dr. Marcus Kehrli (10:16)
back in the 80s and 90s and even into the 2000s, the term epigenetics now refers to heritable changes in gene expression without actual changes in the DNA sequence of the gene itself. ⁓ We now understand that the DNA can be chemically modified by a chemical process called methylation. That doesn't change the sequence of the gene, but it does have an impact on whether the gene is turned on or off.

There can be other types of epigenetic modifications that will also modify gene expression. But for today, we're going to focus on these known methylation effects that can persist across at least two generations and influence traits like liver and mammary gland development, milk yield, fertility, and immunity. Over the last 30 years, Mike, researchers of heat stress in dairy cattle, they've been concentrated in the geographical regions where heat stress is a major recurring problem.

particularly the hot, humid, subtropical areas, the arid hot zones, and even some emergent temperates, hot spots, that get really bad in the summer. So naturally, teams of scientists in the states of Georgia, Florida, and Arizona, they traditionally conducted a lot of research on heat stress. But there's other regions around the world that have similar climates to those states, and they too have been involved. But researchers across almost all regions of the planet today

are actively investigating this topic. So that's a little bit of who and where this research has been getting conducted by and where. So it's important to point this out because heat stress remains an ongoing topic of research that will undoubtedly continue to advance our understanding of this epigenetic regulation of gene expression and the effects it has on health and production. So I'm hopeful this research will actually someday identify how to specifically counteract the undesirable

epigenetic changes that result from heat stress. So next, Mike, let's go over the what of your question. What exactly are the details of epigenetic changes due to heat stress? So again, just to repeat, it refers to heritable changes in the gene expression without any change to the underlying DNA sequence. So the DNA is not changed in its sequence, but there are some things that have happened to the nucleotides. So these non-sequence

Modification allows cells or tissues in the body to respond to some environmental cues such as diet, stress, or even toxins. And these modifications can persist across cell divisions during fetal development. And since the changes can occur in the reproductive organs of that fetus, like the ovaries, that's where the cow's eggs are developed and they can get passed on to the next generation, the chemical changes. So how does a little tiny molecule like a methyl group

that's the methylation, possibly result in epigenetic changes to gene expression. know, a methyl group ⁓ is one of the smallest molecules in biology. It's made up of one carbon and three hydrogen atoms. And that's what gets added to one of the nucleotides in our DNA called cytosine. and that's the cytosine is part of our genetic code and this very small chemical gene

change can have a potentially large biological impact. And it happens in regions of the gene that actually regulate whether that gene is turned on or off at the time. And when you consider the massive size of the bovine genome, which that sequence was completed in around 2009, that genome is 2.8 billion nucleotides long if you lined up all the chromosomes end to end. So the bovine genome is only slightly smaller than the human genome.

actually contains about the same number of genes, somewhere between 20 and 25,000 genes that encode proteins that basically operate how everything works in the body. So what's amazing to me, Mike, is that the scientists doing this epigenetic research, they found that there's about 1500 nucleotide sites that are methylated differently when cows are heat stressed versus cows that have been kept under cooler conditions. And these are found in the fetus.

Importantly, these methylation differences, they map to around 400 different genes. And those genes are involved in various vital functions like mammary gland development, liver development, and immune defense, just to name a few. So when they further analyze what genes were involved, 50 of these genes were shared between the liver and the mammary gland. And that suggests that there's a consistent programming effect across these two organs.

⁓ caused by this methylation. On top of that, in the mammogram there was over 100 genes on top of that that were found to have altered methylation and they could all be impacting gene activity and predictably they would all over milk production.

Mike Donaldson (15:23)
Wow, Marcus, that's a lot of cell biology. Is there another way to explain these epigenetic changes?

Chris Radke (15:26)
you

Dr. Marcus Kehrli (15:33)
Well, let me give it a try, Mike. I realized that was a lot of genetics and biology 101. ⁓ All right. Think of it this way. It's like having a set of instructions written on top of your DNA to tell your genes when to turn on or turn off without changing the DNA code itself. So a cow's DNA is acting like a huge cookbook full of recipes, which are the genes. And those recipes are going to tell each tissue of her body

Mike Donaldson (15:57)
Okay.

Dr. Marcus Kehrli (16:01)
how to build the proteins and do all the things that keep that tissue alive and productive. So every cell in her body has the exact same cookbook, right? But not every recipe is needed in every cell. So for example, a skin cell doesn't need the same instructions as a brain cell or a liver cell or a mammogram cell. And that's where this epigenetics come in. These changes are like sticky notes or highlighters or dimmer switches.

that are attached to the pages of the cookbook. And they can highlight certain recipes. So one particular group of cells in a tissue use them a lot. those genes are turned on a lot. For example, the mammogram cells, they'd be expected to be turning on genes that make lactose, which drives milk production. While if you will, the coronary band of the foot on that cow, it turns on genes to make a hoof instead of lactose.

So each tissue and organ in the body has its own set of recipes that they use and epigenetics, in essence of this methylation, it puts a do or do not use sticker on those genes for each tissue as needed. And there's another really interesting and if you will, somewhat surprising part that ⁓ it may be possible these epigenetic notes that are on there that do pass on to the next generations. Maybe they're not fixed forever, but...

Research and time will tell, but it's possible someday scientists will figure out how we can reduce the undesirable epigenetic changes that have happened under heat stress or other factors. So there are a lot of questions. You know, they can ask, does a cow's diet have the ability to make epigenetic changes for the better? Does exposure to toxins cause these epigenetic changes? There is some emerging evidence that toxin exposure can cause these kinds of changes.

More importantly, can we reverse these multi-generational epigenetic changes that ⁓ cost producers money? So these are all possible avenues scientists can pursue. But for now, the take-home message is, with heat stress, is that the daughter's born to a heat stress cow when they're exposed while it's still in the uterus. They are going to have reduced milk production over their lifetime, reduced fertility, and a shorter herd life.

They have number estimates on that, in a lot of, a lot of factors vary into that, but tend to over 20 pounds of milk production, lower yield per day over their lifetime. The granddaughters that ⁓ were not obviously anything other than a cell or two inside the ovary of that fetus when it was exposed to heat stress, they still have a significantly lower milk yield over their lifetimes. So those epigenetic effects are carried over to the.

second generation after that, so the F2s. Interestingly, if you think about it in another way, epigenetics is actually a big part of why identical twins who have the same DNA for the most part, they end up with different health outcomes if they live very different lives.

Chris Radke (18:50)
Okay.

Mike Donaldson (19:07)
That makes sense. I actually sounds so complicated, but then when you explain it and I think back over different things I've seen, it starts to provide some answers or at least some leanings towards, you know, situations that have played out forever. We just didn't know. We didn't have fancy names for them and we didn't know why. Are there any economic estimates of what these epigenetic effects of heat stress?

and dry cows are costing producers. You see all the time someone has got fans and sprinklers in the holding area. The milk cows are treated like princesses and the dry cows are off in a hollow somewhere doing the best they can.

Dr. Marcus Kehrli (19:55)
Yeah, know, researchers are good at doing research and we, we often use a lot of economic impact estimates. So there's always a lot of assumptions in these numbers, Mike. ⁓ So, and they, and they'll be very specific for everybody's ⁓ herd situation. So ⁓ I don't hesitate to use these numbers, but, ⁓ you know, for the heat stress cow herself, that's getting stressed.

They're going to see a reduction in milk production for the upcoming lactation. Estimates there are maybe average is about 10 pounds of milk per day. But they also expect those cows to have just from this one episode on average, they're going to have a five month shorter productive herd life. And so that'll add up to maybe 80, $90 per cow and direct losses just to that one cow. But for the in utero exposed or the

The fetus that's still in the uterus, the F1 generation, ⁓ their estimates are based on what these studies have shown, a lifetime milk reduction of about 260 to 270 pounds per year per lactation on average. And they also have a lower survival to first calving. So that number ⁓ adds some additional costs. They estimate nearly $160 and extra ⁓ heifer replacement costs.

⁓ because they don't make it all the way to the next generation. ⁓ And then the per daughter annual loss estimates, they range between 370 to over $1,500 over their lifetime. So and add into that the granddaughters, the F2 generation, these numbers do add up.

Mike Donaldson (21:37)
Well, made an administrative decision that because of some of the technical nature of this topic, we wanted to divide this into two phases, two parts. And this is bringing us to the end of what Marcus and I thought was ⁓ a good stopping point. ⁓ So as we wrap this piece up,

Any overall observations on part one, Marcus?

Dr. Marcus Kehrli (22:09)
I think it's very important that we pay attention to this hidden economic cost that we didn't understand or maybe it wasn't as obvious that, you know, we knew we had to cool our cows and provide shade and all that, but ⁓ it's a much longer term impact than any of us probably ever realized.

Mike Donaldson (22:30)
No, I think that's, I mean, and it's funny. It's, it really hasn't been that long ago that some of the things we did were more to keep the people working in the tie stall barns comfortable than it maybe even was the cows and the transitions probably delayed and taking place. So Chris, would this be in part one of your introduction into handling heat stress and dairy cattle? What would you learn in part one, buddy?

Chris Radke (22:58)
My big takeaway is, I know we've said this before, but I'm fascinated with this idea that the things you're doing today is going to affect three generations down line. That whole, I know the big word of the day, epigenetics. I've never heard that word before, so I'll take away that. That environment, that heat is going to affect future generations is fascinating to me. Dr. Marcus, thanks for all you do and all your continuing research. I'm just fascinated with who you are and all you have to give to us. So thank you.

If you like what you heard, like what we're talking about, you can find us on just about any of the social platforms. If you liked us, you can leave us a review, please. And you can find us on our website, agriking.com. And that's about all I have. right. Dr. Marcus and Mike, thank you so much for this part one.

Mike Donaldson (23:44)
Keep watching people, part two's coming out real quick.