9: Literature Review: Impact of Inflammatory Diseases on Fertility

by | Jun 17, 2024 | Ruminate This Podcast

In this episode, Dr. Larry Roth reviews research on the impact of inflammatory diseases on fertility in cattle, focusing on studies from Eduardo S. Ribeiro and Murilo R. Carvalho of the University of Guelph. We will dig into how unresolved inflammation affects every stage of the reproductive cycle—from oocyte development and embryo implantation to the growth of the embryo and calf.

We will break down key findings including the crucial role of the often-overlooked uterine environment in successful pregnancies, the effects of inflammation on developmental biology in postnatal life, and the influence of prenatal inflammation on gene expression in future generations. Discover the dramatic effects of prenatal inflammation on gene suppression, which can impact the health of both the calf and its offspring.

Listen to this comprehensive review that connects research with practical applications to enhance cattle reproductive health and overall well-being. Contact Agrarian to learn how our experts can help you protect your cows from the damaging effects of inflammation. Contact us.

🎧 Listen now to set your herd up for lifelong success!

Scott Zehr

 All right. Welcome everybody to Ruminate This with Agrarian Solutions. I’m your host Scott Zehr. And today I am going to be joined with, none other than the great Dr. Larry Roth. So, Dr. Roth, I appreciate you jumping in today and, visiting with us. Dr. Roth is our Vice President of Nutrition here at Agrarian Solutions. And so far a pretty regular contributor to Ruminate This. So, Larry, again, thanks for taking time out of your day to visit with us.

Dr. Larry Roth

 All right. Great to be here, Scott.

Scott Zehr

 Larry, you know, you and I have talked about a number of different topics on this platform so far. However, there’s something that we’ve looked at recently, a research paper, that really caught your attention.

And this is Ribeiro and Colvalho, the study that was done at that research group. And it’s the Impact and Mechanisms of Inflammatory Diseases on Embryonic Development and Fertility in Cattle. So say that five times fast.

Dr. Larry Roth

There you go.

Scott Zehr

 What we’re going to do today, Larry, if you could, I’d like to kind of walk through some of the results of this study and, just kind of give us an overview of what the study was designed to look at.

And then, maybe just kind of summarize for our listeners, if you could, the outcomes and give us a take home message and how do we think about this, on dairies or as a nutritionist and so on.

Dr. Larry Roth

 All right. Excellent. Well, this is a very good review article. They will get into, some hypothesis of how inflammation affects reproduction. You know, we know that transition hiccups, transition issues will impact first service conception rates. And then that has a long term impact upon financial success of the dairy.

So it all comes back to what can we do to manage these inflammatory diseases. And that goes all the way from making sure we don’t get into subclinical milk fever, to ketosis, to just minimizing the load that comes onto the immune system.

Scott Zehr

 So within this review, what did they discover?

Dr. Larry Roth

 Well, they’re estimating that in the first three weeks of lactation, 60 to 80 percent of cows have some type of a major inflammatory reaction. And some cows are just going to sail right through it. Others, it’s going to linger.

And Scott, you know, I kind of like to use the analogy of a fire. If we have a big fire, we’re going to call the fire department, and they’re going to come and they’re going to put out the fire. But the real problem comes in the smoldering fire that we just kind of allow to linger and don’t come in and bring in a big fire hose and put it out.

But that smoldering fire just lingers and lingers and lingers until the right situation comes along, and then it flames up into a major inferno. And I think that’s a fairly good analogy to use with some of these inflammatory diseases. The cow’s going to get better tomorrow because of the dairy farm. I don’t remember, Scott, is that a thousand and one or a thousand and two things that we got.

And so we’re going to put off treating this cow today because she’s going to get better and we’ll just look at her tomorrow, right? And the problem that comes up is she doesn’t get better tomorrow and we continue to deal with the issues. And the, the inflammation, causes a repartitioning of nutrients.

That’s a fancy way of saying the inflammation is stealing away the nutrients, are stealing away the dollars from what the producer is wanting the nutrients or dollars to go into. And so consequently, the cow doesn’t get better early in lactation, and she still continues to deal with that going way out.

So Scott, we talked about repartitioning or stealing of nutrients. So let’s think about the high production dairy cow. She’s got all the genetic capabilities of producing a whole lot of milk. But, she’s got to have so many nutrients to help the factory live up to its potential.

In the old days when the cows weren’t so productive, yeah, if there was some other challenge that came along, she could much more easily divert nutrients over to dealing with that inflammatory response. But now she’s just right on the edge of the knife.

Right on the edge of the knife. And there isn’t that margin to accommodate the inflammatory drain. Maybe we should call it inflammatory drain on the nutrients. You know, we think about beef cows and we just don’t talk about transition issues with beef cows. We talk about needing to get the cow back onto a positive plane of nutrition, increasing in body condition.

Well, the beef cow just doesn’t have that high a demand of nutrients for making milk. Yeah, she’s got to make milk for the calf that’s standing beside her, but she’s not as finely tuned. She’s not as high a demand. She can tolerate more of the variabilities that come day to day. So certainly beef producers have to deal with all of these things we’re talking about.

It’s just that if we want to think about it, they’re dealing with the old farm truck. They’re dealing with a 1968, you know, pickup that doesn’t have to go 80 miles an hour down the interstate. Doesn’t have to do all of those fine things. It can handle a whole lot more abuse. But somebody who’s driving that fancy Lamborghini that is so finely tuned, that’s a machine that’s designed to go fast. And it just can’t handle the bumps in the road. It can’t handle the potholes like the old farm truck can.

So that’s where I think the inflammation and, the drain of nutrients has become so critical with these high production cows. Now, fortunately, nutrition has come along, management has come along to help compensate for some of this. But if I could step on some toes here for a moment, you know, things like the double offsync program are kind of designed to account for when we have these inflammatory drains.

And things aren’t going the way that they ought to. Well, now we’re going to come in and hormonally, shall we say, readjust the cow.

Scott Zehr

 I think that’s fair. And, you know, I think there’s a place for things like double offsync. But I, I do believe that some of these programs have been developed to cover up the sins, if you would.

Larry, you and I just talked recently about why do we not see as many cystic cows on dairy anymore? Well, we use a lot of GnRH. That’s part of the reason. And so when we, you know, we talked about zearalenone in a previous episode and its ability to impact that, right? I think that the double lobsting program has helped cover some of that up. For better or worse.

Going back to the inflammation conversation and this nutrient drain, you know, one of the things I, I, and maybe I’m jumping too far ahead of you, but one of the things that really stuck out to me in this study was the difference in conception rates in this study. And probably more alarming the pregnancy loss.

I just kind of make reference to it that there was a subset of the cows and I don’t have the numbers right in front of me. But, the animals that had no metabolic issues or had no diseases, experienced, so it was about a 12.4 percent pregnancy loss versus 21.3%.

Dr. Larry Roth

 And I think a follow up on that, Scott, is when does that pregnancy loss occur?

Scott Zehr

 Yeah, exactly.

Dr. Larry Roth

 If it’s very soon after we initially bred the cow. And there I’m using bred as a verb, not as an adjective, you and I have had that discussion. Sso we bred the cow and we have that pregnancy loss. Let’s say within the first 7 to 10 days. Well, that’s bad news, but I think, Scott, the really bad news is if that pregnancy loss occurs, let’s say day 40 or later. Okay? And I pulled day 40 just kind of…

Scott Zehr

Well, I  would say day 30 and later for sure.

Dr. Larry Roth

 Yeah. Because now man, we thought we had her brad now we’re really going to have a delay and when she’s going to freshen again. And the and Another good, good topic. How long should that lactation be? Because if we’ve just lengthened that lactation, let’s say another 30 days, we’ve increased the risk that maybe she carries a little bit more body condition at the end than what she should be. And then we’re maybe we’re setting her up for some subclinical ketosis when she freshens next year.

So again, I come back to the inflammatory drain, the repartitioning of nutrients. What are we doing that messes up the uterine environment? What are we doing that impairs Oocyte development, embryo development? All of those things, I think, when there’s a problem, can come back to some type of inflammatory drain.

Scott Zehr

 We’ve talked a lot about the, different, you know, the different things that are playing a role in causing inflammation. And just quickly, you know, 15, 20 seconds, just review that, and then I have, another question I want to ask you in regards to the study.

Dr. Larry Roth

 Well, I’ll tell you what, a lot of it comes to where’s the site of the, let’s say, bacterial infection. Are we having a bacterial infection in the uterus? Is it in the udder? Are we having a viral problem in the respiratory tract? All of these things will, cause a repartition of nutrients. But probably where we can’t tolerate the infection is in the uterus, because it all comes in to create an as good of uterine environment for the embryo to develop in is what we can have.

So we need to be thinking about what is the timing of the inflammation, shall we say, problem, where is it occurring, and what are we doing to help the cow deal with this and recover from it?

Scott Zehr

 So Dr. Roth if we have one inflammation, one inflammatory disease today, let’s call it, uh, Matritis.There’s longer term effects, than just the symptom we’re seeing today. Right. And it may be decreased appetite or decreased milk production. But there’s also the ability for other issues to creep up out of that.

I’m going to say beyond depressed first service conception rate or something like that. What are some of those things that might happen? Because the door is already open, if you would.

Dr. Larry Roth

 You bet. Oh, good point. So to use your term, the door is already open because we’ve got, we’re dealing with some metritis.

Well, the body can only deal with so many challenges at a time. And you mentioned that intake is down, milk production is down in your example. Well, that’s because the body is diverting nutrients away to deal with this metritis. But the immune system is also having to defend the respiratory tract, having to defend the udder.

So many different things that are going on. Let’s think about the digestive tract. Maybe she consumes some clostridium. Maybe we have some mycotoxins. Any place where there’s a challenge on her body, the immune system needs to go there and respond. But if the immune system is shall we say occupied there with, resolving the metritis, it’s not able to deal with other issues.

And so part of the challenge with inflammation is if it’s not resolved, it can become additive. It can become a bigger and bigger issue because now we’ve got more things to deal with. And that that’s really, I think where the delay in first breeding or the delay, or where a reduced first service conception rate comes into play.

So let’s go back to the time day I programs. Basically is trying to, shall we say, trick the cow into saying, “Hey, I need to get bread here, even though I don’t have all of the nutrients to make things happen the way that they should.” And so maybe we do get the cow bread, but the question then becomes: Does she stay that way? I like to use my little cliche. The main objective here is to get the cow pregnant and stay pregnant.

Scott Zehr

Right

Dr. Larry Roth

And those are not necessarily the same thing.

Scott Zehr

 But I think those things that happen after that initial door is, is opened up. If you would. That’s really, really demonstrated pre partum. If you think about some of the data, say from, that you and I’ve looked at from, Aegis Cow Manager, right? Where we have one bad day in the dry cow program, just off feed for the day. It might be, who knows, it might be two days. Wow, that opens the door for a whole lot of this other stuff.

Dr. Larry Roth

Mmm-mmm.

Scott Zehr

 And so what’s the impact outside of… To me, there’s got to be something more that it impacts than just she’s off feed today and that means she’s a higher risk for developing ketosis or a DA postpartum. But what are some things that we, that may be going on that aren’t actually visual to us?

Dr. Larry Roth

 Right. So, let’s go back to one of my favorite topics, the Britt hypothesis, okay? And so, you know, we could say that what happens, what, 70 to 100 days before fertilization occurs is going to determine if we have an egg to be fertilized, the health of the egg, the likelihood that it’s going to get fertilized and turn into an embryo.

And so, you were just talking about dry cow issues. Well, let’s just say for the sake of discussion, we’re trying to breed what day 70 to day 80. Take 70 to a hundred days off of that. Where are we, Scott? We’re in that dry cow period. And too often we’ve thought that the dry cow period was a time of R and R rest and relaxation.

Now she’s actually doing a whole lot of physiological work. During the dry cow period is the time of greatest fetal growth that takes a lot of nutrients and if those nutrients are being drained away to deal with inflammation, guess what? You know? And now we’re starting to understand that a shortage of nutrients dealing with inflammation has a big impact on turning on or turning off different different genes.

That late dry cow period is also when we’re determining the quantity and quality of colostrum. Well, the immune system is involved in colostrum creation. And if the immune system is off trying to fight some war or wars, guess what? Colostrum is going to suffer. The body, the cow’s body is trying to get prepared for the most challenging day of the year: the day that she freshens.

So if she has these little hiccups, these little upsets that come, pre fresh, those may actually set her up for bigger issues that comes when she freshens and is trying to take off in lactation and is trying to get ready to have a calf the next year. So it’s, it’s also additive. It all builds upon what comes before.

And we just got to get better at identifying when a cow has an issue and helping her resolve that issue as quickly as possible so that the situation doesn’t just continue to increase in degree of a problem.

Scott Zehr

 Right. So, within that study, there was a slide you wanted to share today. And I understand if, if you’re listening to this on the Apple podcast or Spotify, obviously it’s not a visual platform.

All these calls are also available on YouTube, Larry. And, I believe it’s figure seven in the slide and it’s basically, I guess is a diagram of what we just discussed. And I’d like to just ask you to pull that up for our YouTube audience. And again, if you’re listening on Spotify or Apple or other podcast platforms, you can always skip over to YouTube and, and also we’ll figure out a way to make these documents available.

Maybe in the description of today’s podcast call. So Larry’s got this queued up on screen now. For those of you watching on YouTube. And Larry, just kind of walk us through this slide because there’s a lot of moving parts here.

Dr. Larry Roth

 Yeah, there is Scott. There’s a whole lot here that I encourage people to go to Carvalho. Ribeiro & Carvalho. It appears in animal reproduction in 2017. But again, it just goes back to free part of, and Scott, that’s just what we were talking about those free part of diseases start to come up. We’ve got the follicle develop and release the old side. Here comes the most challenging day of the year.

And if we have multiple instances of inflammatory disease occurring is going to affect development at this critical stage here. And I really like how in their figure, they had three different arrows representing three different instances of inflammatory disease. And so it’s kind of a cascade. Things keep trying to develop over here, but we keep having these challenges.

Well, here’s altered energy and lipid metabolism. And Scott, I sure don’t mean to show any disrespect to the authors of this paper. But I, I would just change that to altered nutrient metabolism.  Because we also have protein, amino acids involved. We also have minerals involved. We also have antioxidants involved.

It’s just such a multi factor response. And so all of this is impairing the development that we’ve got going on with Polycle, the oocyte release. We have fertilization taking place. Now we’ve got an embryo that continues to develop. We got the urine environment here. We have the development of the embryo taking place.

And this is where we start to have some of the genes turned on or turned off. And so often in the past, we’ve focused on what’s identified here as, step five as, as being heat… Apparently, heat stress mounts inflammatory response. There’s been much research done on how heat stress affects this calf in utero as well as that calves. Future calves.

Well, we have all types of inflammatory responses that can come on. Might be mycotoxins, might be bacterial, might be respiratory. All types of things that come into play that can either turn on or turn off genetics that affect not only the animal in utero, but also can impact her daughters and, and so on down the line.

So, man, there’s just so much in this graph here. But it occurs on the last page of their article, figure seven. And a person could spend a tremendous amount of time just thinking about how different developments, different situations that occur, going way back to the dry period are going to affect if we create a calf and what type of a calf is eventually born. And what type of an animal that that calf matures into.

Scott, we do a lot of talking here on the heifer side, the dairy replacement side. Everything that we’re talking about here also pertains to, be it the Holstein steer, be it the beef on dairy steer. Everything we’re talking about here also transfers over to the beef side.

You know, we talked about fescue toxicosis with beef animals that are grazing tall fescue that’s infected with the endophyte. That’s where this comes into play right here. So, many different situations can cause the inflammatory response, the altered nutrient metabolism.

And at the end of the day, it determines if we have a calf born and if that calf it’s going to live up to the genetics that were present back at the moment of conception. What genes are turned on, what genes are turned off.

Scott Zehr

 I think that’s the key. And I’ll give some credit over to, our good friend, Jeff Hostetter. Who was on our podcast a few weeks ago and, and just the way he likes to frame it up is the bag of gold coins. And when that animal is, is conceived, when that egg is fertilized and we have a conception, that’s it’s peak genetic potential right there.

And basically it can only go down from there, right? It’s ability to express those genes. And, another episode that I’m talking with Dr. Britt about it’s, it’s epigenetics, right? It’s things that happen to that animal that prohibit the expression of genes.

You mentioned heat stress, you mentioned mycotoxins. You know, there’s a lot of research there on he’s stressed and it affects the cow, the calf, the developing gonads of that calf. But really it’s epigenetics is anything that prohibits the expression of those genes. Larry, that’s overcrowding that’s, not maintaining your sandbags, that’s social effects of moving, moving animals when they shouldn’t be moved.

Boy, there’s a lot of, a lot of things that play into that. Looking at this and talking with you about this, part of me says it’s amazing ee ever get any cows pregnant ever. Part of me says that, you know, it’s amazing. We have animals that are producing a hundred plus pounds of milk a day. And the other part of me says, wow, we’re only scratching the surface of the potential here.

Dr. Larry Roth

 Absolutely. I mean, Scott, everything you said is absolutely true. It’s amazing that the cow gets pregnant. It’s amazing that the calf gets born. It’s amazing that we have cows producing tremendous amounts of milk.

But what if we were able to do a better job of controlling this whole situation? What could we really do to preg rates? What could we really do to help an animal’s live up to their true genetic potential for milk production?

Scott Zehr

So…

Dr. Larry Roth

 That’s the brave new world Scott.

Scott Zehr

 Yeah, and I, I guess my final question for you is what can we do?

Dr. Larry Roth

You know, you mentioned something a little bit ago that so often it gets ignored pin moves. How often do we move the cow? You know?

Scott Zehr

Too many.

Dr. Larry Roth

 Things like heat stress. We’ll put off those fans to next year. We will put off doing a sprinkler system to cool them down. We don’t understand when the cow really comes into heat stress much sooner than what we do. Overcrowding. You’ve mentioned that.

Come on, Scott, can’t we just go up to 125%? Maybe the banker, maybe somebody else is asking us to have more cows there. Is there an impact that comes from all of that? Not only an impact today, but a long term impact.

Scott Zehr

Yeah.

Dr. Larry Roth

I mean, the epigenetics thing is just absolutely incredible. You know, I’m a nutritionist. You come from the genetics world. Man, we can do all this fantastic development with the genetics, but from a nutrition standpoint, a management standpoint, do we allow those genetics to truly express themselves?

Scott Zehr

 I think that’s the, that’s the question that we, we probably should be asking ourselves if we’re, if we’re a cattle rancher in the U.S., if we’re a dairy farm in the U.S., you know, what, what decisions, what practices, what things are we doing today?

And not just how they’re affecting our bottom line today or how they’re going to affect our bottom line moving forward. But what, what effect does this have on our animals abilities to perform the way they’re meant to perform? Cause that’s, that’s really a direct impact to that bottom line, right? It’s…

Dr. Larry Roth

Absolutely.

Scott Zehr

Wow. Well…

Dr. Larry Roth

 Your term, I can get by maybe 140, 150 percent stocking. Well, what’s it going to do to those calves that are born? What’s it going to do to my herd in two years, four years down the road? Well, again, like I said, that’s the brave new world, Scott.

Scott Zehr

 It is. It is Larry. I want to, I guess I have a follow up question for you. Does this, this came up in conversation that I had within the last month here. And it was a herd that is currently dealing with some higher, higher than what we’d like to see toxin loads, mycotoxin loads. And they’re also overcrowded.

And the comment that was made on farm is, was along the lines of, “Well, we don’t feed binders. We haven’t for years because they don’t work. And, overcrowding is what it is around about 135, 140%. But we’ve been doing this long enough that I feel like we’ve just created tough cows. My cows have learned to adapt to it. And that’s why we’re able to make 90 pounds of milk.”

So did this farmer successfully create a bunch of tough cows that truly can overcome mycotoxins and overcrowding?

Dr. Larry Roth

 Well, that’s a fantastic question.The first response is, yeah, maybe we did create a herd of cows that can deal with those situations. But what if stocking was 110, 115%? What if mycotoxins weren’t there?

What if there was a more effective way to protect against mycotoxins than the binders? Are we now talking about a herd that’s 100, 110, 120 percent? Is, does this producer need that 1968 Chevy ranch truck, when they could be creating a herd of Lamborghinis?

Scott Zehr

 You know, it just made me realize that, if there’s ever a good argument for a genetic audit, this would be the farm to do a genetic audit on because what’s your, what’s your rate of genetic gain over the last 10 years, five years, two years?

And, did you create a cow that’s truly tolerant of this stuff? Or did we just create a new, did we move the baseline down? Because these genetics are not allowed to express themselves the way they’re supposed to express themselves?

Dr. Larry Roth

 Wow. That’s a fantastic question. That’s a question for geneticists. Somebody smarter than me. Because my initial reaction is that maybe we have just, lord, the genetics that we’ve got, we’ve selected for a different type of genetics. We’ve selected for a cow that can survive rather than a cow that can excel.

Scott Zehr

Yeah. Good stuff. Well, Dr. Roth, take home message for the audience today in regards to the Ribeiro and Cavalho’s study.

Dr. Larry Roth

 Any inflammatory disease is going to become a drain on nutrients and is going to ultimately reduce reproductive success and has the risk of impairing genetic expression. Read as good a herd as you can, help them get, get as pregnant as be reproductively successful. And then help the genetics express themselves.

Scott Zehr

 Love it. All right. Dr. Roth, appreciate you stopping by on Ruminate This with Agrarian Solutions. And, we will see you again in future episodes. And everybody else, we will talk to you again in two weeks.

Dr. Larry Roth

All right. Thank you, Scott.

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