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Should we monitor the number of ovarian follicles in our heifers and cows?

Before answering this question, we need to understand how follicles are formed and what they do. Follicles are the final stage in which germ cells (oocytes or “eggs”) reside before they are ovulated for fertilization by sperm. There is a long history of cattle research in this area, and one of the most important findings was by B.H. Erickson in 1966 (Figure 1). He found that the greatest number of germ cells in ovaries occurred during the fetal stage. At the peak, there were more than 2.5 million germ cells in the ovaries of fetuses. The number of germ cells or follicles then declines throughout life. Importantly, heifers and cows with more ultrasound detectable follicles stay in herds longer. Herd life is a key component of profitability.
 

Figure 1. Number of germ cells in bovine fetuses during gestation.

Follicle development.

Germ cells are the foundational cells that develop into follicles. A germ cell is an oocyte or egg that will eventually be surrounded by other cells to form a microscopic follicle that will continue to grow until it can be monitored by modern ultrasound devices. As shown in Figure 1, most of the germ cells are depleted before the calf is born, but the newborn calf will still have up to hundreds of thousands of follicles for its future.

Small batches of follicles grow regularly in waves during the late fetal stage, and this continues throughout the heifer or cow’s life. Before puberty, it is possible to aspirate oocytes from the follicles of young heifers, and these can be fertilized in vitro to produce embryos that are then transferred into recipients that have reached puberty.

Once a heifer reaches puberty, generally one follicle will ovulate an unfertilized egg into the oviduct about 24 to 30 hours after onset of estrus. If mated or inseminated, most of these newly released oocytes will be fertilized.

In cyclic heifers and cows, batches of follicles develop to detectable sizes in waves that occur 2 or 3 times during each estrous cycle. Longer estrous cycles are more likely to have 3 waves and shorter cycles are more likely to have 2 waves. One can monitor these waves by daily or twice-daily ultrasound detection, and if the animal is monitored several times daily it is easy to monitor the dominant follicle, which will surpass its cohorts in size before it ovulates.

Postpartum cows that are not yet cycling may show irregular patterns of follicle growth. The ovaries may be “small and smooth” without recurring sizable follicles, or there may be a large persistent follicle that is not accompanied by several normal-sized follicles. This is influenced by postpartum uterine function as well as energy balance.

Why does the number of follicles matter?

If one uses ultrasound technologies to monitor the number of follicles on both ovaries of heifers and cows, it will be found that there is about a 7-fold difference among animals. Nevertheless, the number for each animal is highly repeatable (0.95) https://doi.org/10.1095/biolreprod.104.036277 .

Various research studies have provided evidence that heifers or cows with more ultrasound-detected follicles will stay in the herd longer. Cattle with more follicles respond better to superovulation or oocyte retrieval.

Would monitoring the number of follicles lead to more fertile longer-lived cattle?

Maybe it is time to start monitoring follicle numbers in heifers and cows to determine if there is a genetic basis for the different patterns we see. Heifers with lower numbers of follicles may have lower reproductive life in the herd.

Like any new monitoring technology, there must be some standard practices so that data from different herds are comparable. Monitoring follicle numbers may be easier than one might think. Multiple studies with beef cattle have shown that heifers can be monitored by using ultrasound technologies to count the number of follicles, and this does not have to be done on a specific day of an estrous cycle. This makes it much simpler to collect data at any time once a heifer reaches about 12-14 months of age.

From a practical standpoint, it would be beneficial if we could identify heifers that are more likely to stay in the cow herd longer by monitoring the number of follicles present when these heifers are 12 to 14 months of age. It is too early to know whether this would be valuable in most herds until we have data from many herds across many locations.

The process may be simple. Heifers would be screened by ultrasound evaluation of their ovaries at about 12 to 14 months of age, around the time they are reaching puberty. Subsequently, it would be necessary to correlate the number of follicles counted with important traits such as milk yield, conception rates and herd life. This opportunity, like many others in our dairy selection programs, will only become useful if we find meaningful relationships that are related to herd life and profitability.

 

 

 

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Can We Create Holstein Blood Lines to Feed The World?

Are we missing out on an opportunity to exploit the genetic potential of the Holstein breed worldwide?

Opportunity Knocks

There is already robust global trade among countries involving semen from Holstein bulls and embryos from Holstein cows. This market is competitive and profitable for those that understand its needs and cultures.

Much of this market is in countries that have businesses, organizations and agencies that are members of Interbull https://interbull.org/index. These countries had an estimated 44.5 million milk cows in 2017, based on the UN’s Food and Agricultural Organization. This is a large market, but it leaves out nearly 85% of the world’s milk cows.

Fine Tuning Holsteins

Holstein cows can be found around the world, but when one digs a little deeper to see why there aren’t more, it seems likely that the breed is missing some traits, genes or characteristics that just don’t fit some parts of the world. Maybe there is a lack of heat tolerance or a lack of resistance to some diseases or parasites. Maybe it’s associated with a need in parts of the world for cattle to provide power for ploughing and hauling, but it leaves out nearly 85% of the world’s 290M milk cows.”

Or maybe it is a reluctance of Holstein breeders to break out of there shell of purity to create cattle that will serve much of the world more efficiently. This is no longer a dilemma in some other agricultural species like chickens and pigs because the breeders and breeding companies that serve these species have developed different lines to meet different needs within and among countries. We’ve seen the same thing with soybean breeders where different lines of soybeans have been developed for different latitudes and climatic regions of the world.

Four Cattle Climate Zones

Climate experts have looked at the globe and classified the types of climatic zones that exist worldwide. The experts say we have 5 zones, but only 4 of those are tolerable for cattle. The Polar Tundra may be tolerable someday, but not in the foreseeable future. That means that we have only four climate zones to serve worldwide. Four! That’s right: 4! We even have 3 of those zones in North America. Every continent has at least 3 of the 4 zones. That makes the problem of creating lines for different climate zones simpler.

The global map shows the zones and their locations. We’ve numbered these from 1 to 4 and put numbers in various areas to illustrate the zones within a single country or region. If one looks carefully at North America, South America, Africa, Asia or even Australia, you will see multiples of the four zones.

The Challenge Is Doable

Four lines of Holstein cows! That does not seem too challenging, particularly with the huge amount of global data that we already have and the number of countries around the world that are already engaged in Interbull and similar organizations.

So how do we get there?

First, most of our existing Holstein cows fit well in the Cold Zone (Zone 1). That represents lots of the Northern Hemisphere. We just need to continue focusing on improved health and fertility and enhance components for Line 1.

Zone 2 is temperate, and we’ve generally used housing and cooling technologies to allow Holsteins to do well in these areas. Worldwide there is a lot of temperate land base, and as we see warmer temperatures in the summer in many regions, such as we’ve seen in Europe over the last two years, it may be time to put some heat-tolerant genes in Holsteins in these regions. Some breeders and universities have already done that, but we need to make it easier and simpler to do some crossbreeding to get desirable traits without taking too many generations to be called a “Holstein line”. Today’s genomic tools will allow us to do that more efficiently and effectively, potentially by screening embryos before they are transferred so that we get the most desirable of genes quickly.

The Dry Desert (Zone 3) is filled with Holstein cows today, but there are some traits that could be enhanced for cows in these zones. Solar stress may be their greatest challenge and when one adds that to the internal heat generated by rumen fermentation, it becomes a challenge for the cow to dissipate heat, even in a climate with low humidity. Traits like increased sweat glands, changes in color pattern and even changes in digestion efficiency may be important in these areas. Zone 3 also comprises countries in Africa that have millions of cows. Ethiopia, Sudan, South Sudan and Tanzania collectively have 34 million milk cows! That is a huge marketplace. We need to know a lot more about what traits they need to meet their needs.

The Tropical Zone (Zone 4) is characterized by high humidity and high temperatures year-round. There are very successful dairies in these regions where Holsteins have been crossed with native breeds. They can grow a lot of forage, but often it has lower digestibility. The traits needed in this line are probably already reflected in some of the local crossbreds that one sees. Upgrading those a bit may be a quick way to create this line

Four Holstein Lines – Advantages / Disadvantages

What additional advantages would be derived from creating four Holstein lines?

  • We could greatly enhance the ability of various countries to provide high-quality food for their residents while adhering to some of their traditional practices.
  • We would introduce greater genetic diversity into the breed and potentially prevent “genetic crashes” that could occur because of limited genome sequences in some DNA segments on some chromosome in the breed.
  • We could help our industry be prepared in advance as our climates change and our own farms transition from one zone to another as future generations take over the farm.
  • We could help breeders develop some specialized lines for the non-traditional global market – a market which will grow a lot in the next few decades.
  • Advances in using genomics to evaluate crossbreds will be a big advantage in such an undertaking.

What are the disadvantages?

  • Holstein breeders might begin to look more like hog, chicken and soybean breeders. Is that good or bad? It is probably a bit like reality television. People may not like the concept, but they tune in!
  • The Holstein Associations may have to loosen their rules a bit. They have already discovered that there was a 10-20% error rate in sire or dam ID when genomics started being used broadly. Maybe 100% purity needs to be rethought. If you have an 80% chance of winning the lottery, maybe you would still buy a ticket.

Lines Must be Created Through Selection

Can we do this with gene editing? Nope! Most of the traits that are of interest to us are controlled by many, many genes. Gene editing can work well for one gene, but not for 10 or 20 or 30 that might control some trait of interest. We will need traditional breeding with high levels of genomics before mating and after birth of the calves to do this correctly.

Lines are different than line breeding! Linebreeding typically traces back to a bull or cow over multiple generations. Lines are developed by focusing on certain traits and environmental situations to meet the ultimate needs of the farmers and their customers.

Let’s Get Started

Do our Holstein breeders and organizations have the courage to jump into this pond and swim to the other side, not knowing what is beneath the surface? It is a bit like July 20, 1969. “Tranquility base here, The Eagle has landed.” It was the vision of getting to the moon and back that drove this accomplishment. No one knew how to do it when they started. But they started!

 

 

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Epigenetics will be a Driver for Future Successful Dairying

Dairy breeders spend considerable time choosing the next round of bulls to use. That’s important because improvements in genetics has a significant influence on the generations that follow.  Nevertheless, future performance will depend on how epigenetics regulates the DNA acquired through breeding.  When epigenetics enters the picture,  breeders will need to re-consider how they breed and manage their dairy cattle.

What’s Epigenetics?

Epigenetics underlies processes that affect health, ­ fertility, longevity and many traits of dairy cattle. Epigenetic effects differ from direct genetic effects because the animal’s DNA sequence is not changed by epigenetic processes. Rather, epigenetic processes act by regulating whether genes within DNA sequences are “turned on” or “turned off” without any change in the DNA sequence. (Read more: FORGET GENOMICS – EPIGENOMICS & NUTRIGENOMICS ARE THE FUTURE)

Genetic and Epigenetic Differences

Traits such as milk yield, milk protein, conception rate, somatic cell count and udder conformation are heritable, meaning that differences among animals in these traits can be accounted for by family relationships among sires, dams and ancestors. Heritability ranges from around 3% to over 50% for various traits, therefore 3 to 50% of differences among animals are accounted for by differences in their DNA sequences.

The non-genetic variation in traits is included in what we refer to as environmental effects. Weather, feed, facilities, management practices and everything else that cattle are affected by in a herd fits into environmental effects.  Many responses of cattle to environmental effects are regulated by epigenetic or closely-related processes at the cellular level in animals.

Epigenetic effects do not change an animal’s DNA sequence (genome). Instead, epigenetic effects alter how individual genes or groups of genes are controlled or as geneticists say “silenced or differentially regulated” throughout an animal’s life. Originally, epigenetic effects were thought to represent only alterations that could be passed to the next generation without changing in the animal’s genetic code. More recently it seems that epigenetic effects may impact various tissues and organs during certain periods in the animal’s life, without being passed to the next generation.

Epigenetic Triggers

Animal scientists are using the term “developmental programming” to define practices that may trigger epigenetic effects. Developmental programming may act through epigenetic or similar pathways to influence almost any trait of interest in dairy cattle. For dairy farmers, it matters little whether the action occurs through one mechanism or another, as long as responses are predictable and repeatable.

Repeatability means that there is a fairly predictable pattern of an action causing a specific or response separated by weeks, months, years or generations. That makes it challenging to determine cause and effect, without careful observations, good records and repeated verification.

Epigenetic effects may be triggered by conditions associated with natural biological process or by adverse conditions such as negative energy balance, heat stress, exposure to toxins or other disturbances. Epigenetic effects can be either positive or negative, so as we learn more it will be useful to incorporate management practices that stimulate positive effects and limit negative ones.

Epigenetic Effect #1        Calf Feeding and Future Performance

One epigenetic or epigenetic-like effect is the latent response to feeding higher levels of milk or replacer to heifer calves. Calves fed at higher levels produce more milk in first lactation about 2 years later, so the response occurs beginning about 700 days after the action. Preliminary data suggest that heifers fed more milk develop more mammary epithelial cells that become milk-secreting cells when first lactation begins. This is the kind of epigenetic effect that one would see for stem cells that are dividing rapidly when the milk is being fed. The exact regulatory mechanism for this effect is yet to be determined.

Epigenetic Effect #2        Milking Frequency Immediately After Calving

Similar to the situation in calves fed more milk, it has been demonstrated that cows milked 4X daily during the first 3 weeks of lactation and then 2X daily thereafter produce considerably more milk than cows milked 2X from freshening. The 4X milking early in lactation apparently stimulates development of more milk-secreting cells and these then remain throughout lactation, even when milking frequency drops to 2X.

Epigenetic Effect #3        Embryo Survival

It is highly probable that negative epigenetic effects occur when eggs (oocytes) are developing within the ovary when a cow is under stressful conditions. Such can be the case for the egg ovulated by an energy and/or health stressed cow that comes into heat 80 days post calving. The egg ovulated at day eighty actually started growing as an oocyte within her ovary about 3 weeks before calving.

 Oocytes that develop under these stressful conditions have low survivability as embryos. Their fertilization rate is normal, but they degenerate and die at a higher rate in the first week after fertilization. This is a classical example of an adverse epigenetic effect. Our North Carolina State research team published the first report of this effect in 1992. It is referred to as the Britt Hypothesis and it has taken about 25 years for scientists to begin to understand this phenomenon at the DNA level.

Stay Tuned As We Learn More

There is a strong interest in understanding how epigenetics affect the developing fetus and how management of the pregnant cow influences the future long-term responses of the calf she is carrying. During fetal stages, tissues that will form muscles, mammary tissue, the immune system and all other systems undergo development.  We will see a lot of new discoveries about epigenetics in these areas in the years ahead and this will give us tools to support development of better calves during pregnancy.

Husbandry practices trigger many of the epigenetic effects, both good and bad.  Understanding how such effects are mediated will give us husbandry tools to improve both DNA-based genetics and ways to regulate the DNA in a beneficial manner.

The Bullvine Bottom Line

The Bullvine found that this information shared by Jack Britt assisted us in better understanding the topic of epigenetics.  Yes, epigenetics is yet one more piece of the puzzle that progressive breeders are likely to use in the future to both breed and manage their dairy herds.

 

 

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