[SOUND] Welcome, this is lactation biology course. I'm Dr. Hurley, I'm your Primary Instructor in this course. In this particular module, we're going to be talking about mammary gland development. So some of the structures that develop as the mammary gland develops in the animal, a little bit about the function of the gland and we've got a lot of phases to go through. So, let's take a quick look at all the faces a mammary gland undergoes while the mammary gland is developing. So we see, there's a variety of kinds of phases the mammary gland undergoes in terms of development as well as functional development of the fetal phase. We're going to start out with that here in a few moments. After the animal's born, we have this prepubertal phase when the animal, between the time it's born until it reaches puberty. Postpubertal phase is when the animal undergoes reproductive cycling during pregnancy. And of course, there's a lot of mammary gland development occurring during that period of time. While the fetus is growing, the mammary is grown. Lactogenesis is a functional switch in the gland. All of a sudden, it will start producing milk. Lactogenesis is the initiation of lactation. And then of course, we get over here to lactation which is a lot of what this course is all about in terms of producing milk and so on. At the end of lactation, mammary gland regresses. We call that involution. The mammary gland's really quite unique in the sense that it's one of the few tissues that can actually go through these kind of cycles repeatedly. So it can grow, function, make milk, involute. Grow, make milk, involute with each reproductive cycle, each time the animal gives birth to a new young. Let's focus now on the fetal development stage. One of the main models that we have for understanding how the mammary gland develops in the fetal or embryonic stage is using the mouse as a model. So, I'm going to draw a very crude mouse embryo. So this will be the head, the fore limb bud, the rear end bud. And along in here, kind of right in here right on the flank is a line. Sometimes, you can actually see the line in some species. Sometimes it's more of an imaginary line, but this is what we call the primordia, mammary primordia are going to form. So again, we call those mammary primordia. Sometimes, they're also called mammary anlage and sometimes called mammary rudiments. We're just going to call them mammary primordia for our purposes today. What happens is that different, depends upon the species. So if we're talking about a cow, then these are going to form down here in the inguinal region. So, two on each side. Again, we're looking basically at the right side, right flank of this embryo. Our own species, humans, elephants, they're going to form actually right behind that limb bud where they're going to form up here. And of course, litter bearing species. These things are going to form all the way down, up and down. [COUGH] Now what we need to do to understand what's happening in the tissue is we need to do a cross-section into the tissue and I want to start drawing those here to give you an idea of what it looks like. So, we'll start up here. And they're actually three layers in the embryo. One is called the ectoderm. That's the outer layer. One is called the mesoderm. Mesoderm and there's also an endoderm. We're not going to really talk much about the endoderm here in this particular case. The ectoderm and the mesoderm are two of the key parts of the embryonic tissue that are going to be forming the mammary gland. This is about say, roughly day ten, embryonic day 10. So, it's essentially halfway through pregnancy. Remember in this species, pregnancy is about 19, 20 days. So, we're about at the halfway mark during pregnancy and what we find is at that point that there is essentially a single layer of cells here. Ectademal cells that over lie this mesodermal cells. So, there is a thicker layer here of mesoderm. Not much is going on in that point, this is just prior to when this mammal primordial start forming. When they do start forming, what we start to see is a little thickening. And we start to see a little bit of a thickening in this area and then the mesoderm underneath of it. So, this area in here would be called the mammary placode. Mammary placode and what's happening is not so much that there's cell division causing new cells to be formed, rather the cells that are adjacent to this are starting to migrate into this area causing this thickening, that we're going to call a mammary placode and that's happening at about day 11.5 And then this particular species, it's been studied so much they can get down to even the half day of when do you start seeing these particular structures. We're going to proceed after that and we'll go to the next stage and we start to see more of a bulging, this is called a hillock stage. Again, mesenchymal cells, the mesoderm down here. Again, accumulation of cells up here in this area. And so this would be basically the hillock right here, which we just find the hillock. Again, remember, this is the surface of the embryo. And so, we're digging down into the tissue here. So again, we cut cross section through the outer lying tissues of the embryo. The next stage we want to identify here. Just call the memory bud stage and this is a really important stage. And again, it's starting to sink down into the mesodermal layer. A whole bunch of things are starting to kind of happen at this stage. So what we have is again, this core, the solid core of cells, these are ectodermal cells. We can start kind of thinking of them as epithelial cells at this point. Also, notice that some of the mesodermal cells kind of indicated here. They start to line up, so they actually start to kind of form a lining just on the outside of this bud. And then deeper on out here, the cells that are further down in the mesoderm are starting to form not as precise structure, but they're starting to form another kind of structure. So, this is the mammary bud right here. Again, the outside of the fetuses is here. Mammary bud, this area right in here that these cells and mesodermal cells. We call the. Mammary mesenchyme. The mammary mesenchyme. And again, they're kind of specialized cells. Further down, this area down here, we're going to call the fat pad precursor. So we're starting to get some delineation of different kinds of parts of this mammary gland. Again, the solid core cells are the bud, mammary mesenchyme. So, they started to specialize a little bit in this area. And then addition, these cells will start to specialize too, because they're going to end up being what we're going to call the fat pad. We're going to talk a lot about fat pad for almost every stage of the mammary gland development. [COUGH] What's causing these things to happen? Well, there's certainly lots of things going on here. But one of the key things is that there's a lot of cross-talk between the cells here, the cells in the mammary mesenchyme, the cells down here in the fat pad, especially at this stage between mammary mesenchyme and the ectodermal cells or epithelial cells in the mammary bud. These cells are sending signals to these cells and they're talking back, and forth, and that's what's organizing or orchestrating this development of this particular structure. So let's take a little closer look at this mammary bud stage, because this is the stage at which things really kind of start to happen, start distinguishing between, for example, different sexes and so on and many kinds of things are happening after this particular state. So just to remind you again, the yellow here representing the ectodermal and outer layer on the embryo. Mesoderm would be the brown part here, the middle layer. Again, the idea is that the cells that are in the ectoderm are being recruited into and forming this mammary bud as it sinks down into the mesoderm. We also start to see the blueish, grayish ovals here represent cells that are in the mammary mesenchyme. They start to distinguish themselves a little bit, because they start to line up around at the base or just the outside of this mammary bud and then the fat pad precursor who'd be pretty much the rest of this. We do start to see differences in sexes. For example, female mammary buds typically are a little bit more ovoid versus the spherical. So the one I've drawn here or indicated here is probably more of a male mammary y bud stage, again, represented here as an example of a mouse. The volume of the memory bud is a little bit smaller in terms of the female versus the male at this particular stage. Interestingly, in rodents, rats and mice. This mammary bud after it's formed in the males is actually expelled from the surface and it's gone. So male mice, male rats are born without nipples, without mammary glands, without anything there. That's certainly not true for most species. But in those particular species, that is the case. So, things are going to start moving very quickly. Again, in the next video, we're going to start taking what happens after this and how things start to evolve in terms of fetal development of the mammary gland after the mammary bud stage. [MUSIC]
