To conclude this mini series, Dr. Pete Hansen of the University of Florida presents on the topic of using methyl donors to regulate an early embryo and create an epigenetic effect. This talk was given at the 2022 Tri-State Dairy Nutrition Conference, and is the fourth part of this series.
Guests: Dr. Pete Hansen, University of Florida
To conclude this mini series, Dr. Pete Hansen of the University of Florida presents on the topic of using methyl donors to regulate an early embryo and create an epigenetic effect. This talk was given at the 2022 Tri-State Dairy Nutrition Conference, and is the fourth part of this series.
Beginning his presentation, Dr. Hansen highlights how nutrition can cause epigenetic reprogramming of the fetus. Methyl groups can be added to increase the pattern of DNA methylation in cells and change the phenotype. 3:55
To elaborate on DNA methylation, Dr. Hansen gives the example of placenta vs. embryo cells. A micrograph of both cell types shows that placenta cells have much larger amounts of methylation than embryo cells, indicating that placenta cells are specifically programmed while methylation of embryo cells can still be influenced by the environment. 4:57
Continuing on the topic of methylation, Dr. Hansen discusses how DNA methylation silences specific genes, such as in skin cells or mammary glands. The methylation in the dam can be recapitulated in offspring, representing an epigenetic pattern. 14:42
Opportunities to increase DNA methylation exist. Dr. Hansen points out that altering the environment of an embryo by growing it in vitro for just seven days changes the phenotype. 23:10
How can this knowledge be used to the advantage of the dairy industry?
Seeking to answer this question, Dr. Hansen and his graduate students added large amounts of choline (excellent source of methyl groups) to cultured embryos. They found the addition of choline to increase triglyceride accumulation and DNA methylation. 31:45
After allowing the choline-treated embryos to mature in the recipient cattle, Dr. Hansen and his colleagues found the dams to have longer gestation lengths. This likely led to the higher birth weight of the calves which persisted into weaning. While a high birth weight is not particularly beneficial, a higher weaning weight certainly can be. 36:30
Finishing up his presentation, Dr. Hansen refers to the common animal science equation: phenotype = genetics + environment. He praises the dairy industry’s proficiency in using genetic selection to create better offspring, but he states that improvements could be made in the environment, suggesting that more focus be placed on the prenatal environment. 41:37
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Scott (00:07):
Good evening everyone, and welcome to the Real Science Exchange, the pubcast where leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. Hi, I'm Scott Sorrell. Joining me tonight on the adjacent stool is Dr. Clay Zimmerman. Welcome back, Clay.
Clay Zimmerman (00:24):
Thanks, good to be back, Scott.
Scott (00:26):
Yeah, it's good to have you here. Tonight,we continue our mini series of lectures presented at the 2022 Tri-State Nutrition Conference titled, exploring in Utero Influences on Transgenerational Performance With the fourth and final presentation in the series. Last week, we dropped the third podcast in the series by Dr. Eric Ciappio from Balchem Corporation. His presentation was titled The Growing Importance of Choline in Prenatal Human Nutrition. If you have not listened to that one, please go back and listen to it. I think you're gonna enjoy it. This week we're featuring Dr. Pete Hansen from the University of Florida. His presentation is titled Methyl Donors and Epigenetic Regulation of the Early Embryo. Clay, do you wanna share any guidance for what to look for before we get started?
Clay Zimmerman (01:13):
Yeah, certainly. So, we're, you know, the talks leading up to this, we're really looking at very late gestations, you know, supplementation of, of methyl donors and, and impacts on epigenetics. In this case with Dr. Hanson, he's looking at the very beginning of gestation, really conception. So he's really focusing on the fir and dairy cows the first seven days after conception and the impact of meth, potential impact of methyl donors in, you know, in very early conception. Thanks
Scott (01:50):
For that overview, clay, and let's get right to Dr. Hanson.
Speaker 3 (01:54):
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Dr. Hansen (02:18):
This is a really important topic. I think we in the dairy industry are just starting to think about the consequences of epigenetics, so I'm very grateful for the opportunity to put my 2 cents in. Also, I'm from Illinois, so I've been in Florida 38 years, but I'm originally from Illinois, so it's great to get back to the Midwest. In the time I've been at Florida, I've spent a lot of time working with dairy producers in the state, and recently I've spent a lot of time working with Florida cattlemen. And, you know, Florida cattlemen are very proud of two things, being cattlemen and being from Florida. And my chairman John Arlington, he's from Northern Indiana. He grew up not too far from Fort Wayne, and he spent a lot of his career in extension working with cattlemen. And they're always pointing out to John that he's a Yankee, that he's not really a Florida cattleman.
Dr. Hansen (03:18):
And this is a true story. One day he was arguing with this cattleman and he said, what do you know, John? You're a Yankee? And John says, well, you know, I might be a Yankee, but my two daughters were born in Florida and they're Florida natives. And the cattleman said, John, if a cat gives birth in an oven, nobody calls the kittens biscuits. So I think the one thing that we've learned from listening to Eric and Hena and Dr. Britt, is that the environment of the pregnant female like John's wife, can have a long-term consequence on the phenotype of the offspring. And He showed us some data saying there can be transgenerational effects of the environment of the pregnant female on the offspring. And if there's two points that I want to get across today, it's first that nutrition plays an impact or has an impact on this epigenetic reprogramming of the fetus.
Dr. Hansen (04:30):
It probably does that in a lot of ways, but one of the ways it does it is because the source of methyl groups for Dna methylation, this kind of central event in epigenetics comes from the diet. And it's been shown several times that increasing the amount of methyl groups available in the diet can shift the pattern of DNA methylation in cells. So I think as we move forward, nutrition is gonna be recognized as playing an important role and epigenetics. And the second message I want to get across is that this epigenetic programming of the offspring starts at the very earliest stages of embryonic development. In fact, it actually occurs in the gametes. So the environment of the bull, the environment of the cow before insemination can affect the o site and the sperm in a way that changes the characteristics of the offspring.
Dr. Hansen (05:43):
And that's certainly true during the earliest stages of development, which is what I study. And the reason for that is that epigenetics plays an essential role in controlling how the embryo develops into a fetus and then into a calf. So this is a photomicrograph of a bovine blast assist a day seven embryo. This is the first time the embryo is beginning to differentiate some of the cells. The cells in green are gonna become placea. These are the trifecta derm cells. And then you can see there's a small cluster of cells that are orange. Those are the cells of the inner cell mass that are gonna become the fetus. So I mean, why are some cells green? Some cells orange, because they've been labeled with an antibody that recognizes DNA methylation. So the green cells, the cells that are gonna become the placenta, they already have a lot of DNA methylation, they're starting to get programmed to be placenta.
Dr. Hansen (07:00):
But the orange cells, they don't label with the antibody to DNA methylation. There's a little bit of DNA methylation there, but for the most part, those cells still haven't decided, are we gonna become muscle cells? Are we gonna become skin cells? So there's very little DNA methylation. So if we change the environment of the embryo during early pregnancy, we can potentially change how this DNA methylation gets laid down during the course of development and affect the phenotype of the offspring. So I have three take-home messages. The first is changing DNA methylation during the earliest stages of life. So like in the cow, from day zero to seven, when the embryo's going from a one cell embryo to a blasis stage embryo can change the program of development in a way that affects the postnatal phenotype of the embryo.
Dr. Hansen (08:10):
And then the second point I'm gonna make is providing methyl donors in the diet is one way to change DNA methylation in the developing embryo or the developing fetus. This. And the last one is, there's the opportunity to improve growth, reproduction, lactation, health of livestock by altering DNA methylation at critical times in development. We don't completely know how to do that by any means, but I think the opportunity exists. And what I wanna do at the end of this talk is give you one example of this idea that we can change postnatal phenotype through the diet in the preimplantation period. So I'll show you results of an experiment in which embryos were cultured with choline and then transferred to recipient females. And the growth of the resultant calf were examined. So I think of, I mean, DNA meth epigenetics, super complex. But I just think about it in a very simple way.
Dr. Hansen (09:37):
This is just a representative picture of a gene showing the target gene being regulated by a promoter. The promoter is the part of the gene that acts like it's the light switch turns the gene on or off. So when a transcription factor little TF on it binds that promoter, the gene gets turned on, right? So sometimes the gene is turned on, sometimes the gene is turned off. What DNA methylation does is make that promoter inaccessible to the transcription factor so that even if the transcription factors activated, it can't really access the target gene. And so rather than the cell being able to turn on a specific gene that gene's silenced. And this is reversible, right? It's not necessarily always silenced or always on. So the environment of the cell can affect whether or not an individual gene is methylated and turned off or demethylate and turned on.
Dr. Hansen (10:57):
I mean, that's a lot of what goes on just in day-to-day regulation of all our cellular functions. But sometimes DNA methylation occurs for long periods of time. So like your skin cells, all the genes involved in lactation are probably shut off permanently by DNA methylation. And what makes DNA methylation so important from an inheritance perspective is that these changes in DNA methylation can be inherited from one cell to a daughter cell. So when a cell divides, the daughter cells can replicate the same DNA methylation pattern as the parents' cell. And it can even occur going from the mother to the embryo. So a DNA methylation pattern in the mother can get recapitulated in the offspring. And that's an example of inheritance, but not through changes in DNA. So that's why it's called epigenetics. It's inheritance, but an inherited change in gene function, but without a change in the gene sequence.
Dr. Hansen (12:27):
And so as you change the environment of the cell, provide more choline in the diet, expose the fetus to heat stress, you can change the pattern of DNA methylation. So, I mean, this is just another simple example of showing like one of the functions of DNA methylation. So I'm just looking here at two genes myoglobin, very important gene in the muscle. It binds oxygen to provide oxygen to the muscle cells because skeletal muscle contraction requires a lot of ATP production. You need oxygen for that. So muscle cells produce the myoglobin gene. And then the other gene I'm showing here is beta casein, the main protein in milk, which is synthesized by mammary epithelial cells. So in the muscle cell, the promoter for myoglobin is open and the genus turned on. And once the genus turned on, it produces a messenger, RNA for myoglobin, which then directs the cell to produce the myoglobin protein that binds oxygen. But the Beta Chain gene is shut off in the muscle. The muscle cell does not want to produce beta cain. So probably that promoter is methylated. So the transcription factors would ordinarily turn it on, can't do. So it's more complicated than that, but I think that's a pretty good representation of what happens. So in the mammary gland, you know, the opposite occurs. The myoglobin gene is shut off because of DNA methylation, but the beta casein gene is open. So the transcription factors combined turn the gene on, and eventually the protein gets synthesized.
Dr. Hansen (14:41):
So the first take home message I want to make is that changing DNA methylation during the earliest stages of life can affect the postnatal phenotype, right? The environment of the mother is important for the phenotype of the offspring, even when the embryos just a few cells. So let's look at this a little bit further. This stage of life for the embryo is probably so susceptible to epigenetic reprogramming 'cause the embryo's undergoing a lot of epigenetic programming. You know, think about it, when an embryo is formed, it's formed from a sperm cell, which has the sperm epigenome and a and a cyte, which has the cyte epigenome. But now the embryo, it doesn't want to be a sperm cell. It doesn't want to be a cyte. So the first thing that happens during early stages of development is that all of those DNA methylation marks are removed from the embryo.
Dr. Hansen (15:57):
So if you look at the two cell embryo to the four cell embryo, this is another photograph of labeling for DNA methylation, you can see that there's a lot less DNA methylation in the four cell embryo than the two cell embryo. And the same is true at the six to eight cell stage. That one real bright cell there is a sperm cell, but then new DNA methylation marks get put on because now the embryo is going through development. Some of the cells are gonna become placenta, some of the cells are gonna be the fetus, and those cells need the right DNA methylation to let them function like the kind of cells they're supposed to be.
Dr. Hansen (16:52):
So if we change the pattern of DNA methylation in these earliest stages, we can have long-term consequences for the offspring after it's born. One of the first guys to show this was a guy named Tom Fleming at university of South Hampton in England. And he did a lot of studies looking at the effects of protein nutrition in the mouse, the rat, the rabbit, just during the earliest periods of embryonic development. So in this study, he took female mice minis, made them with Mickey Mouse, male mouse, and then from the day of mating until day three, the now pregnant females were fed either a normal diet for a laboratory mouse in terms of protein availability. So that's a 18% casing diet. Or we had another group of female mice that were fed a low protein diet, 9% casing. And that dietary treatment was just for three days from the one cell stage to the blasis stage.
Dr. Hansen (18:19):
After that, both groups received the 18% Cain diet. And then after Partition, the offspring were raised. And here's some of the results from this one study. A lot of times when you're studying epigenetic regulation in the pre-implantation period, there's a sex effect. Males are programmed differently than females. We don't really understand that, but it occurs a lot of times, and that's what they found. So if you look at the top graph, here we go you can see that comparing the normal protein diet group to the low protein diet group, really no effect on body weight. But in the female offspring, those that were in, females that were fed a low protein diet just for the first three days of life, had heavier body weights at 21 days of age. That's about the time of puberty in a mouse as compared to those fed a normal protein diet.
Dr. Hansen (19:36):
And you see the same thing when you're looking at the ratio of heart weight to body weight. And there's also a blood pressure effect that occurs in both the males and the females more for the females than the males. So just changing the environment, the protein nutrition of these pregnant mice for three days change the characteristics of their offspring. You know, I do a lot of work with in vitro production of embryos. So when we culture cow embryos for transfer into recipients, we are turing, we're culturing them for seven days in a very unusual environment, right? Instead of living in the UCT and the uterus of the cow, they're living in a plastic dish and they're in a medium that is much different than the fluid that they would exist in in the uct in the uterus. Probably all the things listed in that slide differ between embryos produced in vivo and embryos produced in vitro.
Dr. Hansen (20:53):
So in some ways, it's really surprising that in vitro production really works at all, right? Probably about 3% of human babies this year born by in vitro fertilization. They're also exposed to this very unusual condition. And in most cases, I mean, development's fairly normal. The pregnancy rates lower than for an embryo produced in vivo, but still that's embryos established pregnancy. But it is JAK mentioned in his talk. There are some indications that the phenotype of those embryos is different, and occasionally it's like horrendously different. So this is a calf born by in vitro fertilization, that's Rocio Rivera. Now at the University of Minnesota, that calf weighed twice the normal birth weight for a calf at birth. So 200 pounds, and it never stood up. It lasted about two weeks and died. You know, probably about 1% of the calves born by in vitro fertilization have this large offspring phenotype.
Dr. Hansen (22:08):
Something happened to the epigenome of that embryo that screwed up or dysregulated the pattern of muscle growth, skeletal growth later in fetal development. And you get these large offspring of calves that almost always die. Big problem actually. Here's another example of a large offspring calf. Those two fetuses are at 86 days of gestation. The top one has kind of a normal fetal weight for that stage of gestation. The bottom one weighed twice what the one on top weighed and probably had this pregnancy allowed to go to term that calf or that fetus would've become a large offspring calf. So just changing the environment of the embryo during those seven days in a dramatic way changed the way that the embryo grew.
Dr. Hansen (23:15):
So that sounds pretty depressing, but keep in mind, you know, a lot of the epigenetic literature comes from human subjects or from people interested in human health, and they usually focus on the negative effects of developmental programming. How, how your postnatal phenotype can be screwed up if something bad happens to your mother. But not all of the developmental programming is necessarily negative. So if we understand more about the process, I think there's an opportunity to regulate DNA methylation in a way that enhances production. So the second take home message I want to explore is this idea that providing methyl donors is one way to change DNA methylation. That's not necessarily obvious, you know, this is such an important event, whether or not a gene gets turned on or turned off, you wouldn't think that how much methyl groups are floating around would affect DNA methylation.
Dr. Hansen (24:32):
That it'd be much more tightly regulated than that. But in fact, it seems like that's not true. If you provide more methyl donors, you get more DNA methylation. So now in the cattle industry, we have the ability to provide methyl donors to cattle in a way that we never had before because we have rumen protected choline, rumen protected methionine, two methyl donors. Ordinarily those would be oxidized in the rumen by the bacteria, but now we can get them across the rumen and change the availability of methyl donors. In the animal, these two mice are genetically identical.
Dr. Hansen (25:26):
They were both raised, or they were both gestated and mothers that were fed the reproductive toxin BPA and that screws up fetal growth. But the brown mouse was gestated in a mother that was fed a diet really high in methyl donors. Whereas the tan mouse was gestated in a mother that did not receive all those methyl groups. And these mice inherited the auti gene. The auti gene is what gives that tan colored mouse that pretty hair coat. But the agouti gene is regulated by DNA methylation. So when the brown mouse was in a mother that was receiving lots of methyl donors, it's a agouti gene got methylated during fetal life. And so it was brown instead of tan. And also having all those methyl groups blocked the effects of bisphenol A on abnormal fetal growth that the tan mouse was experiencing.
Dr. Hansen (26:45):
So the, these mothers were really slugged with methyl donors. They received choline, folic acid, bane, and vitamin B 12. So, you know, we keep talking about DNA methylation, DNA methylation. What we're talking about is taking a methyl group from denile methionine derivative of methionine and transferring that methyl group, transferring that methyl group to cytosine to produce five prime methylcytosine. That's what we're talking about. So in these mice, this shows one carbon metabolism cycle. Here's methionine, the precursor for five methyl cytosine. So these mice were being fed methionine, butane choline and vitamin B. So given lots of methyl groups in the diet and providing all those methyl groups was able to convert a fetus from this to this.
Dr. Hansen (28:12):
So, you know, can we do that in cattle? That's what I'd like to know. So we've started to explore that question using the in vitro produced embryo. And now we're doing more studies using embryos produced by artificial insemination. But the only data I have right now is for the embryo produced in vitro. So let me tell you about that. So we tested whether or not treating embryos with choline in culture would change the properties of the resultant calf after embryo transfer. So in other words, during this period of development, from the one cell stage to the blasts assist stage, does providing methyl donors in the form of choline program development of these blasts assist so that the result in calf experiences a different postnatal phenotype?
Dr. Hansen (29:19):
Choline is quite an impressive molecule. I mean, it's got three methyl groups, so it's a very good source of methyl groups for DNA methylation. And when it gets oxidized, it gets converted in two steps to beane, which then donates a methyl group to homocysteine to form methionine. And that methionine is a methyl donor for denile methionine the molecule that allows DNA methylation to take place. But choline can also undergo two other biochemical reactions, right? It gets acetylated like Eric mentioned, to form the neurotransmitter acetylcholine, or it can get phosphorylated to eventually produce phosphatidylcholine change lipid metabolism. So when you give choline, you're changing DNA methylation, but you're doing other things as well. So Elia ab Estrada, who was a PhD student with me at University of Florida, he's now banking in his Native Mexico, working with the Ministry of Agriculture.
Dr. Hansen (30:34):
He tested whether adding choline to cultured embryos would change the phenotype of the calves, and that's one of his calves right there. So he did a whole series of experiments. Actually, we never planned on spending as much time on this as we did, but we, he ended up doing this for five years. So the first thing we did was evaluate different concentrations of choline for its effects on in vitro characteristics of the embryo. I won't spend much time on those experiments, but what I just showed you was another picture of DNA methylation and blasis. And when we quantified that DNA methylation, you can see that 1.3 millimolar choline and to a lesser extent, 1.8 millimolar choline increase the amount of DNA methylation in the blast assist, you know, 1.3 millimolar choline, that's a high concentration of choline. Most choline in the blood is present, is phosphocholine. If you sum up all the choline metabolites in the blood of an early postpartum cow, it's about 1.3 millimolar. But free choline, choline chloride, it's only about four micromolar. So I mean, we're adding a lot of choline here.
Dr. Hansen (32:09):
The other thing EAP noticed was an increase in lipid accumulation. So here are embryos stained for lipid in the cells. You can see there's more green, more lipid in the 1.3 millimolar group and the 1.8 millimolar group than in the other two groups. And that's shown here quantified. So choline does at least two things to the in vitro produced embryo. It increases triglyceride accumulation and it increases DNA methylation. So next, ELAP tested whether or not embryos cultured in 1.8 millimolar choline would have a altered phenotype as compared to control embryos cultured without choline. So we did this experiment with brahm and embryos boss indicus embryos, so produced from boss Indicus females and sied by, by Brahman bulls. So then those embryos were cultured either without any choline or with choline. They were then transferred into Angus or braus recipients. And the calves then followed through weaning. So there's one of the calves born from this project a Brahman calf with a surrogate braus recipient female.
Dr. Hansen (33:54):
So here's some results on the pregnancy outcomes. You know, we actually didn't transfer that many recipients, and you need a lot of animals to see a difference in pregnancy rate. And we didn't see a difference that 54% of the controls were pregnant and 44% of the recipients receiving a choline treated embryo were pregnant. And then while we look at calving rate, 'cause some of these embryos are lost before calving, 43% for the controls, 39% for the choline gestation length, if you notice, was a little bit longer for the calves that were produced in culture with choline. Brahmins have very long gestation lengths and it's highly variable. And it was longer for the choline treated calves than for the control calves. So here's a bunch of data on the postnatal phenotype of the calves. And we looked at this data by sex. So we had female calves and male calves, but there were no interactions between choline treatment and sex.
Dr. Hansen (35:12):
So birth weight was significantly higher for the choline treated calves than for the vehicle treated calves. This was true in both the heifers and in the bull calves. So some of that difference was because gestation length was longer. So if we adjust the data for differences in gestation length, there's still a difference in birth weight. But you can see it's about, say, five kilograms in the males and about four kilograms in the females. So still there, but at least some of the difference in birth weight was because of the longer gestation lengths. However, this difference in body weight persisted until weaning. So the weaning weights for the choline treated females was about 13 kilograms, 26 pounds heavier in the choline group, and about 37 kilograms, right? 70 some pounds difference in the ails. So something that happened to those embryos when they were at most 150 cells had a consequence for the weaning weight 13 months later.
Dr. Hansen (36:52):
So that's epigenetic reprogramming. When we looked at the DNA methylation in the muscle of the calves, it was altered by the choline treatment during the culture period. So we looked at 8,000 methylation sites, 8% of those in the muscle were differentially methylated. And when we looked at the genes that are associated with those DNA methylation, differentially methylated sites, those were genes that were involved in cellular growth in muscle function, like the mTOR signaling pathway was regulated. So changing the em, changing the environment of the embryo in terms of providing more choline, change the birth weight of the calves and change the weaning weights at seven months of age. So, you know, how practical is what I just showed you, there's not many embryos produced by in vitro fertilization. The number are increasing, but I think it establishes the idea that we can change the environment of the pre-implantation embryo, the very early embryo, and affect the phenotype of the calves in a beneficial way.
Dr. Hansen (38:27):
And I can tell you Florida producers, they don't want calves of larger birth weight but they do want calves of larger weaning weight. So, you know, I just remember when I was an undergrad at the University of Illinois, I think the very first course I took was animal Science 1 0 1. And the very first module we got this back in 1974 was genetics. And I never forgot this equation, that the phenotype of an animal, how much milk it produces, how much it grows, how healthy it is, depends upon its genetics and its environment, right? Everybody knows that. And you know, as an animal scientist, I'm very proud of the work. All of us in the academia and in industry have done to change the parameters of this equation so that we've made tremendous progress in producing a more efficient animal and a more sustainable system for producing milk, for producing meat than I was a than, than was the case when I was a undergrad back in 1974. We are really good at genetic selection. We know how to identify genetically superior individuals and propagate them. And we have learned a lot about how to raise animals, how to change the environment of a calf or change the environment of a cow so as to optimize its expression of the genes that inherited to maximize or optimize milk, yield growth rate, et cetera. I mean, there is the change in genetic merit for milk yield from 1960 to 2020. I mean, that is tremendous progress. The genetic merit for milk yield has doubled in that time.
Dr. Hansen (40:51):
What I would suggest is all of our emphasis on changing the environment of livestock has been after they're born. And like I say, we've made tremendous progress in optimizing that environment. But we haven't yet really thought we're just starting to. I mean, some of the data that Jimena showed you today is an example of that. We're starting to think about how the environment of the embryo, the environment of the fetus, can affect the postnatal performance of the animal once it's born. And so I think that's where epigenetics is gonna play an important role in letting us further enhance production by optimizing the environment of the offspring before it's born. So I'll just end with a couple of photographs. I want to thank all the people who did all the work that I talked about today, especially with this project with the Brahman embryos.
Dr. Hansen (42:01):
Jeremy Block from University of Wyoming was critical with that. Here's the farm crew in the lower corner. Chem supported some of that research. The Florida Cattlemen's Association, even though I'm a Yankee, supported some of that NIH kind seat. And I will tell you that we're still working on this. So I have a new graduate student, Laney Haman. She's continuing to do studies with embryo transfer to see if we can repeat the effects of 1.8 millimolar choline. And we're also looking at more physiological effects of choline chloride. So we're treating embryos with four micromolar choline 0.004 millimolar choline. So those studies are just being done. We have some birth weight data from another experiment with 1.8 millimolar choline, and we saw the same effect. And then m for Sge, who's in the red here is starting to look at what is the effects of feeding rumen protected choline from one day before breeding until seven days after breeding on characteristics of beef camps. And we'd like to do the same thing in dairy cattle. So I'll leave it there.
Scott (43:32):
Clay, Dr. Hanson presented some heavy duty science and some very new concepts. Would you mind summarizing some of the key takeaways for us?
Clay Zimmerman (43:42):
Yeah, so, so again, you know, he's looking at very early gestation, right, right after conception up, up through day seven after conception. So, you know, his hypothesis is that, you know, if we can improve DNA methylation and basically from the one cell to the blast assist stage in dairy cows, that we could potentially improve growth reproduction and or lactation in the offspring that are born at that point. So so, you know, DNA methylation can change the development of that, the post postnatal pH phenotype that's being inre expressed. And, you know, he is really looking at optimizing the environment of the offspring and, you know, very, very, in the very, very, very early stages of, of gestation and, and how, you know, providing methyl donors can, could potentially impact this.
Speaker 3 (44:51):
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Scott (45:14):
You know, I found it interesting, clay, that, so this will take place right around breeding time. So what about day 100? So we're gonna have to take a different look on how we're supplementing choline to dairy cows. Any thoughts on that and how that might play out?
Clay Zimmerman (45:28):
Yeah, it's a great question and it, you know, it's a bit of a challenge, but you're exactly right. You know, we really haven't looked at supplementing choline at, you know, at this stage of production. So we're gonna have to think about that some more. You know, first of all, what levels need to be supplemented? We don't really know that yet. And then, you know, for, for what length of time. But once we get answers to a few more of these questions that you know, we will definitely have to address that as far as how to actually get that, you know, into these cows. But there's certainly some promising research there at this point. It's still in its infancy, I would say, you know, as far as looking, looking at this specifically. But he, Dr. Hanssen continues, continues to do work to, to look at you know, supplementation of methyl donors right at conception.
Scott (46:30):
Yeah, clay, this has been a very enlightening series of presentations, which is why we decided to share them in a podcast series. If you'd like to view the full webinars and slides, you can find them at balchem.com/realscience. Simply scroll down to April 27th, 2022. The title you'll see there is the 2022 Tri-State Dairy Nutrition Pre-Conference, symposia Exploring in Utero influences on Transgenerational performance. Click the link and all four of the pres presentations will be there for you to view and just click on the one that you want to see. Clay, as always, it's been fun spending time with you here at the Exchange. And I want to thank you for all your help on this important series.
Clay Zimmerman (47:16):
Thank you
Scott (47:17):
As always. To our loyal listeners, thank you for joining us for tonight's conversation. We hope you learned something. We hope you had some fun and hope to see you next time here at the Real Science Exchange, where it's always happy hour and you're always among friends.
Speaker 3 (47:32):
We'd love to hear your comments or ideas for topics and guests. So please reach out via email to anh.marketing at 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 anh.marketing at balchem.com. Balchem’s real science lecture series of webinars continues with ruminant focused topics on the first 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.