Guests: Dr. Jack Britt, Jack Britt Consulting; Dr. Jimena LaPorta, University of Wisconsin-Madison; Dr. Eric Ciappio, Balchem Corporation; Dr. Pete Hansen, University of Florida; Dr. Clay Zimmerman, Balchem Corporation Today’s episode was filmed live and in-person from the Tri-State Dairy Nutrition Conference! This episode will focus on the symposium exploring in utero influences on transgenerational performance.
Guests: Dr. Jack Britt, Jack Britt Consulting; Dr. Jimena LaPorta, University of Wisconsin-Madison; Dr. Eric Ciappio, Balchem Corporation; Dr. Pete Hansen, University of Florida; Dr. Clay Zimmerman, Balchem Corporation
Today’s episode was filmed live and in-person from the Tri-State Dairy Nutrition Conference! This episode will focus on the symposium exploring in utero influences on transgenerational performance.
Dr. Jack Britt started by saying when managing your dairy herd, if the cow is pregnant, you are managing the next three generations simultaneously. We need to be focused on the long term in how we care and feed the animal. (5:10)
Dr. Pete Hansen mentioned breeding for heat stress is challenging because there is so much movement of cattle across the U.S. However, there is genetic regulation of resistance to heat stress and how cells respond to hyperthermia. Dr. Hansen believes dairy cattle breeders will start to put out heat tolerance genetic data. (15:15)
Dr. Eric Ciappio has studied the role of choline in human pregnancy and its increase in infant cognition. While there is currently no direct data supporting choline fed in human pregnancies will also help the child’s immune system as it does in cattle, you could someday make that assumption. (25:48)
Dr. Clay Zimmerman shared a study that showed improved ADG through ten months of age when supplementing the cow with choline during pregnancy. Furthermore, the benefit was seen in utero, with less improvement but still some coming from colostrum. (38:19)
Dr. Jimena LaPorta said that her research focused on understanding if you can reverse heat stress in utero. Heifers born to heat stress cows were cooled and provided the opposite environment, but they didn’t recover. They responded to the treatment physiologically, but growth wasn’t recovered. (44:28)
Dr. Jack Britt wrapped up by emphasizing the importance of a single compound like a methyl group and how it could have a huge influence on the biology of an animal. You can look at big things, but we also need to look at the little things. (1:04:24)
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This podcast is sponsored by Balchem Animal Nutrition and Health. This podcast is sponsored by Balchem. All views expressed by the guests are the opinions of those individuals and are not the views of the Balchem, its affiliates or employees.
Scott Sorrell (00:00:07):
Good evening everyone. And welcome to the real science exchange. In the podcast, we're leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition at the science ex uh, real science exchange. We like to that, uh, we, we meet in a virtual pub with real drinks. Typically we are, uh, meeting, uh, on a screen. We see each other on a screen, but tonight that's not the case. We try to recreate the atmosphere that takes place after a scientific conference. Um, that takes place in the pub over a few drinks with, uh, good friends and colleagues, but tonight we don't have to. So, uh, pretend we're actually after a real science conference. So that's awesome. Uh, and with friends and colleagues, so we're looking for a, uh, arousing, uh, discussion tonight. We even have an audience looking forward to having some discussions, and questions from them as well would encourage them to participate. Um, I mentioned that we are at the tri-state nutrition conference, where we just had a, uh, a symposium on exploring in utero influences on transgenerational performance, and with us tonight with our panel first, we have, uh, Dr. Jack Britt, Jack, would you mind, uh, introducing yourself, tell us a little bit about yourself and then what are you drinking tonight?
Dr. Jack Britt (00:01:20):
Well, I'm drinking whiskey. Uh, I'm a retired professor. I worked at Michigan state university at North Carolina state university, and also the University of Tennessee. My specialty is dairy cattle, reproduction, and management. And I have a future team that looks at the dairy industry 50 years in the future.
Scott Sorrell (00:01:41):
Now, uh, I forgot to mention that your title for your talk today was epigenetics will change how we manage cattle. Uh, also to my, uh, right here is Dr. Lia porta. Um, and your topic was, uh, yeah, phenotype and, and molecular signatures of fatal hyperthermia. Tell us a little bit about your, and then what are you drinking tonight?
Dr. Jimena Laporta (00:02:05):
I am drinking a fruity cocktail, which is good. I recommend it. Um, I'm Jim porta. I am an assistant professor. I'm not retired yet. Um, an assistant professor in lactation physiology started my career at the University of Florida, uh, spent their five years and now, um, I of two years I have been in at the University of Wisconsin, Madison.
Scott Sorrell (00:02:27):
I noticed before you had a whiskey old fashion, what happened with that? Is it just, wasn't your liking
Dr. Jimena Laporta (00:02:31):
It? Wasn't Brandy. So had to pass. There you go. Sorry,
Scott Sorrell (00:02:36):
Brian. We need to fix the next one. All right. And to my left, my trustee, uh, and talented. Co-host Dr. Clay Zimmerman clay. Tell us a little about yourself and what are you, uh, drinking tonight?
Dr. Clay Zimmerman (00:02:49):
So, I'm the, um, director of technical services, uh, for BAS animal nutrition and health, uh, division. And I'm, I'm drinking a, a captain and diet tonight.
Scott Sorrell (00:03:02):
Oh, awesome. Sounds good. No, uh, uh, cider this time they, they
Dr. Clay Zimmerman (00:03:06):
Didn't have any, and hard cider,
Scott Sorrell (00:03:08):
No agree. Orchard, no angry clay. All right. Got it very well. I forgot to mention clay that your title, uh, the talk, uh, was prenatal colon supplementations role in calf performance. Uh, next speaker is, um, Dr. Eric, um, capo, no capo, capo, capo. All right. And, and your talk is a little bit different. It's, it's not, uh, anything to do with dairy science, but the growing importance of the colon in prenatal human nutrition is very interesting. Tell us a little bit about yourself and then what are you drinking tonight?
Dr. Eric Ciappio (00:03:39):
Sure. My name is, uh, Eric capo. I'm a part of the nutrition science team here at Beach. I'm on the human nutrition side. Uh, I am drinking a diet Coke, and the reason I'm doing that is that my wife is pregnant in preparation for today's talk. I think she was being very supportive
Scott Sorrell (00:03:59):
Very nice, very nice.
Dr. Eric Ciappio (00:04:01):
She, uh, you know, team capo.
Scott Sorrell (00:04:02):
Yeah, she is on colon though. Yes, she
Dr. Eric Ciappio (00:04:04):
Is. Yeah. Copious amounts.
Scott Sorrell (00:04:06):
Yeah. Good job. All right. And then our final speaker was, uh, Dr. Pete Hansen. He had meth donors and epigenetic regulation of the early embryo. Pete, tell us a bit about yourself, and then what are you drinking tonight?
Dr. Pete Hansen (00:04:18):
Yeah. Hi, I'm proof of, uh, animal reproduction at the University of Florida department of animal science where I've been there for 38 years. So I'm drinking whiskey. Yeah. Make young maids frisky.
Scott Sorrell (00:04:36):
Excellent. Uh, I've got a whiskey as well. Uh, Buffalo trace, I think, you know, I heard, uh, well actually Jack and I had a couple of Buffalo traces last night. We were practicing
Dr. Jack Britt (00:04:45):
For this today. Right. That's what we were doing.
Scott Sorrell (00:04:47):
Dr. Jack Britt (00:05:10):
Sure. When we look at a cow that's pregnant, uh, we think about the cow as being one generation and the calf in utero being the second generation at that calf in utero also has ovaries or testes, and they have the germ cells for the third generation. So when we're managing a herd, if the cow's pregnant, we're managing the next three generations all at the same time. And so we have to have a long look in terms of how those gonna be the car for and fed and what kind of nutrients they receive for them to be healthy and productive.
Scott Sorrell (00:05:49):
Excellent. You know, I enjoyed your presentation. I like the story that you told about your twin brother. So maybe you could kind of recount that story again.
Dr. Jack Britt (00:05:57):
Yes. I I'm a twin and twins are alike identically, genetically. And if we look at their DNA, the methylation or the changes in the DNA that may occur, uh, they're absolutely the same until they're moving until they move apart from each other. At three years of age, the DNA is the same as at 55 years of age, uh, that I used to compare with my brother. Uh, if you look at the DNA and the methylation on the DNA, it's different, significantly different among twins because the environment that they lived in over the time they've been apart has a significant effect on how their DNA functions. And I think that's a very important, uh, concept that we don't understand very well.
Scott Sorrell (00:06:49):
Now, during our pre-game discussions, you had a, uh, a very interesting question for, uh, Dr. Hanson. Do you wanna ask that one again?
Dr. Jack Britt (00:06:58):
Uh, we, I ask about splitting embryos and if they would, if we could make twins and would the, would those two embryos, if the two cells were split into twins, would they develop the same?
Dr. Pete Hansen (00:07:10):
Right. Thank you, Jack, for that question.
Dr. Jack Britt (00:08:10):
Well, it's the same as looking at young twins who are identical, right. And then looking at the same twins when they're 50 years old and they're always different right. At 50 years and always the same at or three years. So, uh, yeah, they, they probably are the same kind of, uh, changes there. Yeah. Yeah.
Scott Sorrell (00:08:28):
Carrie, do we have any questions for the audience?
Mark Fox (00:08:30):
I Mark Fox, uh, a dairy vet in the thumb of Michigan for 38 years too. And you are, look just like your twin brother, so
Dr. Jack Britt (00:09:21):
Let me start with the transition cow disease, we do have too much transition cow disease. We think we can manage that, but I think the long-term solution of that is genetics is that we, we need to be looking how to breed cows, that don't have that big transition loss in body weight and still produce, uh, lots of milk. One of the trends we see is an increase in protein and an increase in fat, which is what we need in the industry to produce products. So maybe we can stop putting as much focus on volume and put more focus on components and, uh, accomplish that goal
Scott Sorrell (00:10:04):
Jima. We had a discussion or question there about, uh, heat stress. Can you talk a little bit about how heat stress derails, the ma gland development?
Dr. Jimena Laporta (00:10:11):
Absolutely. So I didn't show too much of that data today because I wanna overwhelm everybody, but, uh, we see that heat stress during gestation leg gestation, really derails the epithelial cell component of the PERMA tissue. We see fewer epithelial structures there that are gonna become the future secretary cells. We also see less, uh, PERMA, not only the PERMA but also the fat pad, which is the support of that, uh, epithelial structure as the mammary gland develops is gonna grow into that fat pad. So if you have a less fat pad, to begin with, then you're gonna have a problem. And I think those early life development stages, we don't tend to think a lot about. And as I said today, in my presentation, we start thinking about that heifer when she's reached puberty, and then we start thinking about her mam land, but I think there's a lot of focus shifting now into those early life developmental stages and even nutrition during the pre winning period and impacting Mai growth. And I think heat stress is, is one of those stressors that can derail development. And we see consequences in multiple lactations. So those early life developmental windows are really important. And we have to start thinking about them more. So,
Dr. Pete Hansen (00:11:36):
Hey, manna, if I could just, yep. Ask you a question. So we know that the placenta's disrupted by heat stress. We know that the place has a big role in the development of the memory gland of the pregnant cow. Do you think those placental hormones that are regulating memory development in the pregnant female are having any effect on memory development in the fetus, or are there other causes besides that for the,
Dr. Jimena Laporta (00:12:08):
That's a great question. I think, um, the impairment in the placental development, it's impacting the calf as a whole, right. Fewer nutrients, less oxygen, less, less everything. Um, I think the placental development has a direct impact on the cow ma and that has been shown, you know, the connection between placenta, placental function, and ma development, the cow. Um, so I, I do think that there's an impact there. I do not know, and I think it will be a nice, um, segue to study is how the, uh, placental dysfunction impact the Marick none of the offspring directly maybe, um, you know, less estrogen, less gesture at that early life stage might have an impact. I'm pretty sure that it will. Um, but showing that connection, the direct connection, it's quite challenging.
Dr. Clay Zimmerman (00:13:30):
Hey man, I wanna follow up, uh, with the question you, you mention that the circulating IgG levels were lower in these calves that were born to the heat, and stress dams. Yeah. Why do you think that's occurring?
Dr. Jimena Laporta (00:13:44):
I think we hypothesize that the gut has a lot to do with it. Then, the development of the gut in Ute star a little bit earlier in, in utero heat, stress, CALS. And so those cells start dying. And so there's kind of like an early, um, I G G absorption event occurring. And so once they are born, they have, uh, fewer cells in the gut that are proliferating. And I instead our dying. So gut closure starts a little bit before. So we have shown that more cells are dying in the gut, uh, in those in tres calves. And so they have less ability to acquire those immunoglobulins from colostrum. So if you give them the same colors from the same amount of IgG in the colostrum, they absorb 20% less. So I think in utero heat stress is somehow accelerating that gut closure and, and, and then that's why they have that. And it's not just at birth it's throughout the pre winning period that they have lower IG. So there's, it's, it's, it's a long-term effect.
Scott Sorrell (00:14:59):
You might not feel like we're picking on you, but
Dr. Jimena Laporta (00:15:01):
I, I, I need a drink
Dr. Pete Hansen (00:15:03):
One second, cause she's an expert. She's done this before.
Dr. Jack Britt (00:15:06):
I wanna ask Pete, uh, talk about heat stress. Do you think we should be breeding cows that are more heat Toler?
Dr. Pete Hansen (00:15:15):
Yeah. Well for sure, you know, it's a little bit difficult to do in the United States, I think because there's so much movement of cattle across the country, so they can Florida, for example, probably a third of the replacement heifers come from outside the state. So it's, it's, it's difficult to select cattle genetically for resistance to heat stress. But I think in other parts of the world where that would not be an issue it's, I mean, it's clear that there's genetic regulation of resistance to heat stress, both in terms, of the body temperature during heat stress, but then also in how the cells respond to hyperthermia. So I think, yeah, I think we can, you know, not only can we select for genetic resistance to heat stress, I think you're gonna see, uh, um, genetic estimates of thermal tolerance start to put out by all the major, um, dairy cattle breeding organizations.
Dr. Pete Hansen (00:16:22):
You're already seeing that in Australia. And I just predict you're gonna see that in us. The one problem we have is that um,
Scott Sorrell (00:17:21):
Dr. Hansen, while you have the floor, um, during your presentation today, you talked about, uh, the fact that, um, uh, DNA methylation around the time of, uh, fertilization and then about cell after what's the best way or how can we get nothing donors into the cattle, uh, at that timeframe?
Dr. Pete Hansen (00:17:42):
Well, I guess you have to buy reassurance
Scott Sorrell (00:17:45):
Well,
Dr. Pete Hansen (00:17:46):
I mean, I mean I think, you know, that's, that's what makes this whole, that, that that's what makes us have a conversation about providing mental donors to ruminants. Yeah. Is the ability to bypass the Ruen.
Scott Sorrell (00:18:00):
Yeah. So no, I appreciate the question or the answer, but
Dr. Pete Hansen (00:18:04):
I was, yeah, I was just teasing there, but you know like I was talking to Eric earlier and I'm sure he'll comment about it. It's a lot easier to provide nonruminants, like, like women with Colleen through the diet than it is, uh, ruminants species, but you know, because of the technology we have available.
Scott Sorrell (00:18:23):
Yeah. I was thinking more around timing, right. So when a cow's bread she's around what a hundred days in LACT or so hundred 20 may be longer and we're not typically supplementing colon at that time. And so my question kind is how, how, how long do you have to be supplementing either colon or methyl ahead of, uh, fertilization,
Dr. Pete Hansen (00:18:45):
If I had to guess, I think you have to supplement it ed fertilization. Okay. I'm not sure that if you feed coal in the transition period, there's that much coal stored in the body stores, 70 days later, to be able to influence, uh, coal concentrations in the reproductive tract. You know, the same is true for Metin where, I mean, free probably disappears within a couple of hours after feeding and gets incorporated into tissues as amino acids. So my, you know, it's an issue in terms of making the feeding of meth donors practical for altering, uh, properties of the calf. So I guess what we have to figure out is, you know, what is the cost of feeding the colon versus the benefit that results from whatever the changed phenotype is in the calf?
Dr. Jack Britt (00:19:45):
What if we, what if we put it in the semen?
Dr. Pete Hansen (00:19:48):
Ooh. Yeah, I think about that all the time. You know, there there's like I study a lot of molecules that regulate their early embryo, but to inject those in a cow is expensive. And because you're trying to influence the concentrations in the reproductive tract, you know, which might weigh what 10 kilograms, but you gotta put it in a 500-kilogram animal to do that. So you gotta administer huge doses. And, and of course, every time you touch the animal that costs money. So if you could develop a delivery system in semen that would cause slow colon or other bioactive molecules, that would be great. And I, I'm not, I don't know anybody doing that right now, but I think
Dr. Jack Britt (00:20:45):
We put an, we put antibiotics in now that's so, so we have other ingredients. Yeah. Other than just sperm,
Dr. Pete Hansen (00:20:51):
But when we put antibiotics in, we want them to last 24 hours. Yeah. If we're gonna put a colon in, or let's say I Gone or bro hormonal, we want it to last seven days. Sure. Right. The embryo doesn't even enter the uterus until day four, day five. So we have to come up with a slow-release method and you know, there's been a lot of, I'm not a pharmacologist, but I just heard a seminar on Thursday about the slow release, uh, of vaccine products. You know, there's a lot of pharmacology has been developed to achieve slow release of molecules according to the way that you wanna achieve the increase and decrease. So I, I think, yeah, there's some opportunity there that we should be looking at.
Dr. Eric Ciappio (00:21:50):
If you look, um, at a moderately analogous situation, if you consider human nutrition requirements or for met donors during pregnancy, or pre-pregnancy the classic example that you're going to get is around folic acid for the prevention of neural tube defects. Right? So if you look at the public health recommendations that generally fall in that women should start taking folic acid supplements about three months before conception. Right? The reason is twofold. One is behavioral. One is physiological. One is that takes some time for folate status or meth donor status in this case, uh, to increase, right? So hence the three months and second is because women generally don't know that they're pregnant for the first month or so of pregnancy. And at that point, the neural two generally already closed around day 28. So if you take that lesson, I guess if I may hazard a guess into the dairy nutrition world of which I've got about five hours of exposure, so
Scott Sorrell (00:23:05):
Yeah. Thank you for that. Eric, why don't you give, uh, the audience, uh, at least the ones that aren't here today, kind of just a real brief overview of what you talked about today and why in the world is a, a human, uh, dietician on a dairy nutrition panel.
Dr. Eric Ciappio (00:23:18):
Do you get a non, a lot of non-human dieticians giving, uh,
Scott Sorrell (00:24:00):
Hmm. Very interesting. So H how, how different were differences, right. I mean, I, I saw the graphs, but I, I didn't know. How do you measure that? Were they, were they compelling? I guess that would be a word I would, I would describe it as, or were they marginally compelling?
Dr. Eric Ciappio (00:24:16):
No. So in infants, uh, you did see a significant difference in, uh, what they measured effectively was a reaction time test. And so you do see some significant differences there now from a clinical perspective. I mean, it's always difficult to try and assume how that might translate in terms of infant behavior because that's such a, a subtle finding in a sense, but at the same time, these small differences that are set up can have associations with behavior later in life that is more measurable and more practical to see. I mean, when you look at epidemiological data, you do see, so that there's a significant difference that persists, um, with the association of colon intake from mom and visuals, spatial memory in the offspring, and then even our data shows that the impact of supplementation Causely did increase the ability to maintain a child's attention over time, which children are not known for their ability to pay attention to one thing for any given period. Right. Mm-hmm
Scott Sorrell (00:25:29):
Mm-hmm
Dr. Eric Ciappio (00:25:48):
Not necessarily immune function, not for, um, uh, not for colon anyway. Um, if you consider the growth of, If you consider the growth of the function of the brain, improving with colon supplementation and by extension, that means there must be some biological change that's occurred, right? Be it epigenetic or genetic or physiological, or what have you, I would argue that, yeah, there must be logical, you would assume that there's some kind of a change in growth and development that's occurred as a function of, uh, colon supplementation, just because you see these effects cognitively in, in the offspring.
Dr. Pete Hansen (00:26:24):
I'm always shocked. It takes us so long to do these developmental programming experiments in cattle. I mean, you know, nine months for the gestation one year for the calf to grow up nine months gestation for the calf, and then it's lactation, but that's nothing compared to studies on the human, right. You would have to take those children into at least the teenage years or adulthood. And I'm sure it'll happen. Mm-hmm
Dr. Jimena Laporta (00:26:59):
Life. Right. And I think to add to that, I, I think we have a very, a very powerful tool in our hands with dairy, because if you think about human studies, then once that baby's born, they're gonna be exposed to, you know, different diets, different if they breastfeed or not, you know, there's a more heterogeneous environment for them. Whereas in cattle, we have a very homogeneous progression of events, especially nutrition and management. They're most of them are in the same facility for years. And so, and we milk them whether they like it or not, you know, when they become cows. So we have a more homogeneous phenotype, I think. So that's why I think we have a good Case, no hands.
Dr. Pete Hansen (00:27:45):
I used to work with a guy who studied puberty and sturgeon and takes the sturgeon 25 years to reach puberty. So he's, not a good project for a master's term
Dr. Clay Zimmerman (00:27:58):
So
Dr. Pete Hansen (00:27:58):
That is a limitation right everything we do takes a long time and
Dr. Jimena Laporta (00:28:02):
Lots of money too
Dr. Pete Hansen (00:28:03):
Mouse and ran studies take a long time to study the adults.
Dr. Clay Zimmerman (00:28:08):
So, Eric, what are the current recommendations for colon supplementation, um, in humans during gestation and lactation?
Dr. Eric Ciappio (00:28:18):
So the current guidelines are really to follow the adequate intake, uh, for colon, for pregnant women, which is, uh, just over 400 milligrams a day. Um, there's although that's kind of the general sort of state of the art, I guess, from the Institute of Medicine, that's somewhat of a dated recommendation. What you do see, however, is that most women do not meet, that adequate intake requirement. So there are some statements from some major authoritative bodies within the field of the dietary guidelines, uh, the American medical association, American academy of pediatrics, et cetera. Um, and they do, um, advocate trying to meet that requirement for the colon. Now, certain academics of course, uh, will have their own opinions about what the specific DRI should be and in the light of some growing evidence. Nevertheless, right now, um, the AI is sort of the magic number to hit. Uh, but even that is still a challenge
Scott Sorrell (00:29:12):
Very well. I think we have a question for the audience.
Speaker 8 (00:29:14):
Yeah. Um, I'm not sure who this question would go to, but basically what you were saying, um, early in the presentations was that methylation of genes can have a, uh, downregulating effect. Is there a known upside to that as far as the survivability of that animal, say in a wild environment where the mother happens to go through stress,
Dr. Pete Hansen (00:29:39):
You know, there is for sure. I mean, silencing a gene is not always bad. I mean, most of your genes are probably not most, I don't know how many are in a given tissue, but many of them are silenced. So I mean, there are genes that are probably active in all cells and then genes that are active just in specific cells or tissues and then genes that are periodically turned on or off, like, you know, the LH gene for during control of the Astro cycle. So turning a gene off by itself is not bad. And, and, you know, we don't completely understand what we're talking about, so, but inappropriate activation or inappropriate silencing that becomes bad.
Speaker 8 (00:30:28):
So I guess my question was in these situations where the dam is under heat stress and, and you look at the pattern may be of methylation, do you see, is it, is it kind of random or is there could a person say, well, I see how that would help that calf. If they were living in a wild, she's not gonna help the producer of milk, but it might be helpful.
Dr. Jimena Laporta (00:30:50):
Yeah. So that's a great question. I, I showed a handful of genes just, to give an overview, but it's a lot more complex than that. And we have, uh, methylation in the promoter, which is what we're more used to seeing. Okay. If it's methylated in the promoter, it's gonna be silenced, but we have methylation all over the genome that we certainly don't understand, um, what that does. Um, and we have methylation in, in introns. Um, and there's a lot more research coming from the human side, showing that methylation, even introns is quite important in regulating, uh, gene expression. And so it is a lot more complex. And, uh, some of the genes that I showed are methylated in the promoters. Um, and so, therefore, we, we assume that they're gonna be silenced, but obviously, we have to show that and we have to prove that, and we have to see what are the effects we show phenotypes that relate to something bad, you know?
Dr. Jimena Laporta (00:31:53):
Um, so that heat stress, um, silencing some genes exert in, uh, negative phenotype, cuz everything I showed is could be considered negative. Right. Um, but yeah, I think it's a lot more complex and this panel can talk more about that. But, um, methylation not only the promoters exist and do we know, is it one cytosine, two cytosines, three cytosine that needs to be methylated to, to see an effect. And so I just want to bring out to the table that, we certainly don't understand a whole lot on what direction do we go with this methylation?
Dr. Pete Hansen (00:32:33):
So, I mean the father of this field is sir David Barker also from the university of south Hampton. And he studied all these children who were fetuses during the winter of 1944 in Holland. And so their mothers were starving and when they became adults, they had all sorts of increased disease incidents, incre, especially metabolic diseases like diabetes, and cardiovascular disease. So he's thinking, which I think dominates the field today is that all this developmental reprogramming, all the epigenetic reprogramming is designed to prepare the fetus for the life it's gonna experience after it's born. So maybe it's thought, oh, I'm gonna be in a really hot environment. I have to turn these jeans on. And these turn off. And then when it's born, it's in an environment where the producer wants it to produce as much milk as possible. And I, you know, I think there's some of that in developmental programming that it is not an error. It is adaptation. It's just that when we try to fit it in the production system, it becomes, um, undesirable.
Dr. Jimena Laporta (00:33:50):
There are different theories yeah. And different names, silver spoon hypothesis, three 50 phenotype hypothesis that depending on what the environment was in utero, whether that gonna help out or it's gonna become a negative, uh, fitness adaptation to the animal. So yeah,
Speaker 8 (00:34:09):
I guess my last part of that question is, do you, is there anybody who's looked at, whether it affects genetic recombination because if you, it seems like if you methylate DNA, it might affect like, affect how that crossing over and all that stuff, uh, happens later on
Dr. Pete Hansen (00:34:26):
That's. Yeah. That's a very good question. You know, as far as I know, like recombination rate and cattle, it's only been measured a few times. I mean, there has not been a lot of you, probably 10 to 20 crossing events, crossover events during myosis. So it's not that many, but I mean, your point is yes. A fascinating one, cause yeah, that's a very good idea.
Scott Sorrell (00:34:52):
Great discussion, Eric, during your presentation, you talked a little bit about, um, how Colleen helps with, uh, the transport of DHA and a, if that's exactly the right term, uh, term. But I, I, I was intrigued by that and I was wondering if, you know, in, in dairy nutrition, we're doing a lot of work now in very specific fatty acids and the impact that they can have, um, on, on biology. And I found myself thinking, boy, it would be great to have a, you know, a fat, um, guy on the panel, but we, we don't have one of the
Dr. Clay Zimmerman (00:35:24):
On right here.
Dr. Pete Hansen (00:35:26):
What are you talking about? Not
Dr. Jimena Laporta (00:35:29):
Here.
Dr. Pete Hansen (00:35:32):
Our mothers took very good care of us when, well,
Scott Sorrell (00:35:39):
I was actually kind of taking a Dr. Poque out there.
Dr. Jack Britt (00:35:42):
Scott Sorrell (00:35:43):
Is it alright if I call a friend,
Dr. Jack Britt (00:35:45):
Let me tell you, my mother, my mother did not know I was going to be born. She did not know. And the doctor did know, did not know that she had twins and this was before any of the technologies. And so after the doctor had checked my brother out to make sure he was okay and checked my mom out, he said, I need to check you out. And he said, oh my God, there's another one in here.
Dr. Pete Hansen (00:36:12):
This one's gonna be,
Scott Sorrell (00:36:17):
Um, no, but I just kinda expound on the question. I'm just curious if, if you know, we're doing a lot of, um, uh, of work and I'm just curious if Dr. Palmquist has any, any thoughts on that and co helping with the transport of other fatty acids and what impact that might have on the gal biology, uh, sorry to put you on the, on the spot there, doc
Dr. Pete Hansen (00:36:37):
Speaker 10 (00:36:39):
Um, since you ask, um, I haven't looked at Colleen's metabolism specifically, but we did look to see what happens with an increasing amount of feeding fat. And as you do that, you increase the fossil lipids in the blood the lot, um, I question I could ask is, could we stress the cow out for coal or methyl donor supply by feeding too much fat? Um, and the other is by feeding fat, do we provide enough coal to not be an issue?
Dr. Eric Ciappio (00:37:14):
Yeah, that's a really interesting point. I mean, I don't know that we've come at it from the angle of if we adjust dietary fat, what does that do to colon requirements other than I guess the natural experiment of looking at depletion, depletion studies and humans, which are not known for having low-fat diets, generally speaking. So when you look at the folks who even under replete conditions, where they're getting the adequate intake of the colon, some still do have liver dysfunction, which would suggest to your point, they just don't have enough colon to meet their requirement. Now, whether that's some genetic condition or if that's just a function of excessive fat intake, I don't know that that study or those depletion studies were necessarily built to accommodate that question because they were relatively small. But I do think that's an interesting idea, right? Is it a supplier demand problem or is it just something in the architecture of us as the way we were built? So I think that's, that's an interesting approach
Scott Sorrell (00:38:13):
Clay. We haven't had a chance to talk to you much today. Why don't you give us a kind of an overview of your presentation?
Dr. Clay Zimmerman (00:38:19):
Yes, so, my presentation was about the, uh, the effects of maternal supplementation of Colleen, on the calf. And, uh, we've run a series of experiments at the University of Florida shows, uh, positive benefits, uh, primarily in utero benefits that are occurring in the calves born, uh, to dams that are supplemented with calling during the last three weeks of gestation. So we've seen improved average daily gain out through, out through 10 months of age and, and all, all the way to fir uh, out to first caving, um, in heifer CALS. And, uh, there was a study run with bull CALS, uh, submitting them to an LPs challenge at 21 days of age and showing improvements there as well in outcomes in average daily gain, um, after LPs, uh, supplementation. So, most of those benefits that we've seen, are occurring in utero. Those last three weeks, there are, uh, we've seen a little bit of improvement and some of the work, um, that have come from, um, from the colostrum side of things, um, from the colostrum produced from these, uh, supplemented dams
Dr. Jack Britt (00:39:48):
Clay, uh, in, in the transition period, particularly the last three weeks, you know, feed intake drop tremendously gets low in the last week or so do we need to be changing the supplements that we put in the dry cow feed for every week for the, for the three weeks before a cabinet?
Dr. Clay Zimmerman (00:40:13):
It's a great question. Um, we don't manage the cows that way. No, typically we could, we could, it's a really good question. Um, I would say overall, I don't, I don't think we see as much of a decline in dry or intake as we did maybe 30 years ago in, in, in these, uh, close-up dry house. Then there's still some, some intake depression, but I don't think it's quite as dramatic as what we used to see. Maybe
Dr. Jack Britt (00:40:45):
We just increased choline for the three weeks before in the last three weeks of the drop
Dr. Clay Zimmerman (00:40:50):
Period, right? Yeah. Yep. It's a, it's a great question.
Scott Sorrell (00:40:56):
You might wanna kick it back over to, uh, Humana, um, in keeping with our, our, uh, our theme here, how long, or how many generations does heat stress impact, uh, the dairy cattle,
Dr. Jimena Laporta (00:41:11):
As far as we can tell, um, three generations three, if we, if you use Dr. Red's, um, you know, classifi, but I, I, I refer to it as F zero Fone and F two. So the daughter and the granddaughter. So those are three generations. Um, and it comes down to what he stated in the, um, opening today, uh, that during that time we have those three generations that we're impacting. So that's why we see down the road, those effects because you are, you have them all at the same time in those last 60 days. So
Scott Sorrell (00:41:47):
Have you done research beyond
Dr. Jimena Laporta (00:41:49):
That? I have. Uh, so actually when I moved from Florida to Wisconsin, I took 40 halfers, 40 F ones that were generated in Florida. Um, so I put them in a truck, took them to Wisconsin and they're pregnant now. So we are generating the F two and we are gonna be able to track the phenotypes because the data we have is retrospective data, uh, 10 years worth of studies that we could gather 50 animals, 50 F twos. So now we're gonna be able to get our hands dirty and get some data, molecular data, and PHY data. And those, but what's striking is that we still see differences in their growth and, um, pure the attainment. And, um, even after taking them all across the country right. And different environments. And so you still see those differences. So that makes a think that what happens in Ute during that time stays with the animal regardless of the environment, is that was, it's one of the concerns, right? Like you're changing the environment postnatally, so that can wipe off those differences, but it doesn't look like it. So it's really interesting. I'm very curious to see what we get with these F twos soon. That'd
Dr. Clay Zimmerman (00:43:08):
Be interesting.
Dr. Jimena Laporta (00:43:09):
Stay, stay tuned.
Dr. Clay Zimmerman (00:43:10):
So Hema, you, you were showing a, a milk production graph from the, from the F two generation. Yep. And it looks like if I remember that graphite about 15 weeks into lactation, they start to separate. Yeah. Why do you think that's happening at 15 weeks in lactation?
Dr. Jimena Laporta (00:43:29):
I have no idea. That's a great question. I, I think, it does impact the mama Al cell turnover. Right. So, um, but I'm just speculating there. I, I don't know. I, I wish now with these F twos that I can get, you know, liver BI, uh, mammary biopsies, and answer that question, but I do think that it's impacting the ability of those cells to proliferate. And that's when you see that crash, that persistency really, um, affected, they reached the peak, and then they just crash. So
Dr. Pete Hansen (00:44:06):
Mainly so, I mean, it can affect the heat stress to extend generation. So can we repro ran that animal? Is it doomed ever because it was exposed to heat Smith utero, or can we reverse that program?
Dr. Jimena Laporta (00:44:28):
That's a million-dollar question. So if you find the answer, let me know. Um,
Dr. Clay Zimmerman (00:45:56):
So there's a 10% reduction of birth, weight mm-hmm
Dr. Jimena Laporta (00:46:10):
That's another million-dollar question I'm gonna get reached today? Um, I think five days, it's, it's pretty significant for growth. Um, I've seen work in pigs that they are, uh, inducing, uh, partition, uh, at different times. And they see how the growth of the, that it's impacted by that. I have not seen that working cattle, and it's, it's quite difficult to, to do that, to prove that, you know, those five days are, are not, uh, driving, uh, the differences that we see. Um, but yeah, I, I, I have, no, I don't have a fair answer to that if, if that's a big deal, but if anyone has any thoughts
Dr. Eric Ciappio (00:47:00):
Would be interesting, uh, thinking about, I guess, both of your respective presentations. I mean, you had talked about, uh, Randy J's work on that a boot mouse, right. And they showed that the effective epigenetic insult, which is the BPA exposure was effectively rescued with meth donor supplementation. And then you look at your work and you showed that, uh, heat stress led to a lot of different, uh, methylation abnormalities and things like wind signaling pathways. Right. Which are known to be impacted by, uh, meth donor restriction. Right. So it seems like at least maybe a, you know, the shot in the dark perhaps would be that perhaps there's an opportunity to try and at least rescue, or perhaps minimize that phenotype with sufficient meth donor exposure during, uh, the gestational period.
Dr. Jimena Laporta (00:47:44):
Absolutely. Yeah. I think that's doable. I will have some data for you in a few months.
Dr. Eric Ciappio (00:47:50):
Oh, you're fast.
Dr. Jimena Laporta (00:47:51):
Dr. Jack Britt (00:48:21):
What happens in the room. And if you have non-protected methyl, donors, is the bacteria just chop those up and use them for something else?
Dr. Clay Zimmerman (00:48:34):
Yeah, yeah. For the most part. Yeah. There's only, so in the case of Colleen, Rick Erman, did that work back in the late 1980s and only about one person, one to 2% of it makes it through the room and intact. Yeah.
Dr. Pete Hansen (00:48:53):
But does that change the, I mean, where, where do, where does colon come from in a cow? That's not getting reassured, right. I mean, it's synthesizing Cho, but it's probably, is it getting bacterial choline? And if you'd feed Cho to the room and micro-organ, do you increase they're in the corporation of coal and get more coal from the bugs themselves? I, I, I don't know, but I don't know what the metabolism of choline
Dr. Jack Britt (00:49:22):
Is. Well, yeah, they're, they're, they're digested downstream. So if you could get more into the microorganism, maybe you also get,
Dr. Clay Zimmerman (00:49:32):
Yeah, well, there's some more work being done on that area right now, but yeah,
Scott Sorrell (00:49:38):
Very well. Carrie, do we have a question for the audience?
Speaker 12 (00:49:41):
So, um, I'd like to explore a little bit about your, um, the Brit hypothesis and how it connects to this discussion. So if I remember the hypothesis correctly, the recruitment of the primary follicle or, or oy was a, I think you said 110 days in your, yeah. So if we, if we put methyl donors into the animal at the time of recruitment
Dr. Jack Britt (00:50:27):
You know, that's that, that's a very good question. Um, just as a, as a basic, uh, acknowledgment, all of the follicles are all the eggs that a cow will ever have occur when she's a fetus. I mean, it reaches the maximum of maybe when she's in the six months of pregnancy and starts going down then on, uh, so those resting Eyes are resting follicles, if you will, are activated. And we don't know why, why do we have some activated in some nonactivated, you know, we've got, we've got two or three cycles of activated follicles every three weeks or, or every week. And, um, I think the methylation is associated with once the O site reaches the stage of ovulation. Now it can, it, it can be damaged during that development. And maybe if we back up if we just fed higher levels or had had higher levels of coaling the whole time it developed, but it takes about a hundred and a hundred days, 110 days. And that that's kind of similar among several species, not mice, but, but larger species. Uh, so, um, I, I think the critical period is just at, or during fertilization in its first five or six days of development, as, as Peter has mentioned that that's the critical period. Yeah.
Dr. Jimena Laporta (00:52:04):
I have a comment, on that because we, we, we say, you know, the effects on the second on the F two are due to the potential of talking about heat stress, but impacting that rest in all side, that will become the F two, right. The second generation. But during fertilization, you both talk about that those effects are wiped off those epigenetic marks most. So that's, that's my, and, um, are some of them immune to that wiping off. Uh, so that's the only explanation I see on why we see, um, those effects in, in the granddaughters.
Dr. Pete Hansen (00:52:42):
You know, there are a few genes, the imprinted genes where only the father's copy or the mother's copy is expressed. So even though you inherit a copy from Danny, a copy from mommy, depending on the gene, only the father's copy or the mother's copies are expressed. So the epigenetic mark that's, let's say silence is the father's copy that gets inherited. So, um, there, it's not a complete erasure. And, you know, for, I showed those large camps, a lot of people think those are imprinted genes that are being dysregulated. So there, there is some inheritance it's not well understood. Is it all just the imprinted genes or is it other genes, but it's not com the only time it's completely wiped off is in the primordial germ cell is the, you know, when Jack talks about the fetus has an ovary, or the fetus has testes, those primordial germ cells before they become Oyes before they become sperm, they have all their marks wiped off.
Dr. Jack Britt (00:54:05):
And that, and
Dr. Pete Hansen (00:54:06):
That's the only time when that happens
Dr. Jack Britt (00:54:08):
In the cow. That's about the, uh, fifth month of pregnancy when the Fe is about five months old, it'll have a maximum number of, uh, germs house,
Scott Sorrell (00:54:19):
Dr. Hanson for the audience that wasn't here. Can you talk a little bit more about those large calves? It's, it's not necessarily a good thing, right? It's a, it's a very bad thing. Yeah,
Dr. Pete Hansen (00:54:26):
And so we produce embryos in vitro in a very artificial environment. We, we provide all the salt sugars, amino acids, they're living on plastic instead of in a UC and uterus and amazingly, usually off, I mean, I shouldn't say hugely many of the embryos that are formed from that, um, can establish pregnancy a little bit lower rate than, uh, for embryos produced in the cow and, and develop normally and produce normal offspring. But maybe 1% of the time, um, fetal development is greatly disrupted, especially development of the skeletal muscles, probably the skeleton, and you get this large offspring syndrome it's called or abnormal off syndrome where the cabs are probably about twice the normal size. So, I mean, we, we've had 130 pounds CPO cabs born this year, you know, huge twice the size. And, um, they're not, that's the most obvious phenotype they're really big, but they also have other characteristics, you know, their, their four legs are bent.
Dr. Pete Hansen (00:55:56):
Sometimes they have a very big tongue and that is, uh, reminiscent of, uh, syndrome and humans called crater Willie syndrome, where, uh, fetal development's abnormal, there's a lot of severe mental retardation associated with that, uh, syndrome, but also the children have, you know, really big tongues. And it seems to be an imprinting error that, uh, this one imprinting center that controls these genes that cause crater, Willy, uh, are abnormally regulated. And that disease is more common in babies, human babies born from IVF. So some people think, I mean, we don't know. Some people think that what happens with the large offspring syndrome is similar to the crater, Willie, that some imprinted genes don't get
Scott Sorrell (00:57:55):
We're getting close to the end of our time here. I wanna, yeah, there are close.
Speaker 13 (00:57:59):
Dr. Pete Hansen (00:58:00):
Thank you.
Scott Sorrell (00:58:02):
You all saw that the light Sid flickered that is the last call. Um, and as part of the last call, what I'd like to do is ask each of you to kind of share two things. One is, uh, give us an idea of something you learn today from one of your fellow speakers. Uh, and, and then two, give us an idea of something that, uh, the nutritionist veterinarians in the audience today, uh, listening as they're driving down the road through the podcast, what can they do? Uh, what, uh, from things that you guys learned today that they can take home and use at their dairy farms, uh, tomorrow, and why don't we start with up then?
Dr. Pete Hansen (00:58:35):
Well, I mean, I think what they can use is really what I Maya's gonna talk about. I mean, Amanda probably has the best example of the importance of the developmental programming for, for, uh, dairy cattle production. You know, don't heat stress. We always ignore the dry cow and put her out in the middle of nowhere. That's dumb,
Dr. Eric Ciappio (01:00:07):
Um, I, I learned probably more than anybody, I think, uh, since this is my first exposure to the, to the dairy nutrition world, but I think what I, what I've got a greater appreciation for now is just how impactful the role of early life nutrition is. And that's a that's not a human-specific phenomenon. That's something that is, I think, just, just conserved across all mammals. Um, and, and I think we're only scratching the surface with this too. I mean, we all talked, you know, in some way, shape, or form about methylation, but that's only one avenue that epigenetics plays a role. I mean, um, even our work with Colleen shows that cooling deficiency can lead to Everett micro RNA expression. That's something that is, is just, I mean, still super new. I mean, micro RNAs are only discovered in what, less than 20 years ago.
Dr. Eric Ciappio (01:00:55):
So I mean, imagine where we're going to be in 20 years and the, how we'll be able to describe this relationship between nutrition and epigenetics. So I would say, I mean, if I was to, to give some 10 million foot high advice to a dairy farmer, I would say that, um, paying attention to adequate nutrition, be it, you know, for humans that are working, uh, working in your operation or for the dairy cattle that are there is incredibly important. And I think the preconception gestation time is probably the most impactful time to pay attention to nutrition at any point in the lifespan,
Scott Sorrell (01:01:34):
Well said, clay.
Dr. Clay Zimmerman (01:01:37):
So the take-homes for mine, um, we we've known for years now, uh, certainly two buckets of benefits to supplementing reassured, to transition cows increased milk and milk component yield and improve liver health and overall health outcomes. But the, um, the third benefit we're finding now is, is impacts on that developing calf, um, that's happening the last three weeks of the cast. So those are the take-homes from mine as far as, as far as what I learned today. Um, I, as far as Pete's, uh, presentation, we, we do need to figure out how we can, uh, properly supplement these meth donors during, during, um, the, the time of fertilization and conception
Scott Sorrell (01:02:30):
Mm-hmm
Dr. Jimena Laporta (01:02:34):
Um, I learn a lot too. I, I learn a lot about the large offering and syndrome, which I think is fascinating to think that, um, methylation can cause that, and, and I think that's a fascinating topic. I did learn a lot about the colon, just other than being a meth donor, all the things that it can do. So, uh, there's, there's a lot there as far as both on the ground for my research. I think Pete summarized it very well. So thank you for that.
Dr. Jimena Laporta (01:03:29):
Uh, and it will take years, you know, we're in, understanding how, how they work. But sometimes when we say programming or manipulating people, get it a little, um, upset, but I, I think those are the things that are gonna come in the future. We know the genes now we know how to now we need to learn more how to manipulate them, uh, to our benefit and to get, uh, positive responses. So managing that dry cow, not just we, we show that cooling can revert all these pH types that I showed, but also nutrition, uh, or a combination of both, which maybe it's not one thing or the other. Maybe it's the two of them. And so, yeah, just looking at your dry cows and those three generations that you are impacting. So next time you think about a dry cow, think about three generations and hopefully, you don't forget about that. Yeah.
Scott Sorrell (01:04:20):
Thank you. Let you on it.
Dr. Jack Britt (01:04:24):
I would say in 20 years we will have net merit for epigenetics, just like we have net merit for genetics for all of our breeds of cattle, uh, and other species. And, and I also learned how important a simple compound, like a methyl group, can have a huge influence on biology and animal. I think that's important that we look at, all the big things, but we also need to look at the little things. Metal groups are extremely important. So thank you for this opportunity.
Scott Sorrell (01:04:56):
Uh, thank you for that. Uh, guys, ladies, this has been a treat, uh, you know, the real science, the inspiration for the science exchange has been conversations just like this, that I've been participating, uh, participant of over the many years, whether it's been at the tri-state Cornell nutrition conference, a DSA, uh, it's, it's met all my expectations that this has been a lot of fun. I appreciate it. Wanna thank you, uh, you guys for, uh, for participating today, I wanna thank the organizers of the tri-state conference. One of the best there is out there. I also wanna thank our loyal listeners. Uh, we appreciate you. We appreciate, uh, all the kind comments that you give us. And we hope to see you next time here at the real science exchange, where it's always a happy hour and you're always among friends,
Speaker 15 (01:05:38):
Cheer. Cheers. Cheers.
Speaker 16 (01:05:41):
We'd love to hear your comments or ideas for topics and guests. So please reach out via email to anhmarketing@balchem.com with any suggestions, and we'll work hard to add them to the schedule. Don't forget to leave a five-star rating on your way out. You can request your real science exchange. T-shirt in just a few easy steps, just like, or subscribe to the real science exchange and send us a screenshot along with your address and t-shirt size to a and h.marketing at bache.com. Baches real science lecture. The Series of webinars continues with ruminant-focused topics on the Tuesday of every month. Monogastric-focused topics on the second Tuesday of each month and quarterly topics for the companion animal segment, visit balchem.com/realscience to see the latest schedule and to register for upcoming webinars.