The ovarian cycle

- We're gonna talk about the ovarian cycle. The ovaries are two structures in a female's reproductive system that produce her eggs. Each month her eggs go through a maturation process called the ovarian cycle, and that cycle creates a secondary oocyte than can be then fertilized by a sperm to result in a pregnancy. The ovarian cycle is also responsible for what we commonly know as the menstrual cycle. Basically, the primary oocytes that are destined to be ovulated will develop in the ovaries, complete meiosis one just before ovulation, and then they'll be ejected out of the ovary as a secondary oocyte to be picked up by the fimbriae and swept into the uterine tube to hope for fertilization. So let's start from the beginning. Inside the ovaries, eggs develop in structures called follicles, these purple circles here. And they start off as primordial follicles. And so what a follicle is- I'll just blow that up for you- It's one primary oocyte, so an egg cell, surrounded by a layer of cells called granulosa cells. And the granulosa cells develop and become more numerous as the follicle matures. Now the granulosa cells also secrete a few hormones. Estrogen, a little progesterone and some inhibin, and we'll talk about the functions of those a little bit later on. So let's put a timeline on this. Now the ovarian cycle lasts 28 days. This is day zero here at the primordial follicle, where we're going counter-clockwise. All the way over here, this is day 13. Here, where the secondary oocyte gets ejected, or ovulated, that's day 14. And then the rest of the time spent getting back to the primordial follicle stage are days 15 through 28. So now you have an idea of about how long this all takes. So you remember when we said that the granulosa cells produce hormones? Well, as the follicles develop over the first 13 days, and you can see the changes between the one here and the one here. It's got a lot more purple cells around here. Those are granulosa cells. So the number of granulosa cells goes up, and since they produce hormones, what do you think happens to the hormone levels in the blood? They go up. So that's sort of just a general point. So keep that in mind, but first we'll jump back to these. We know these are primordial follicles here. The next stage of development are these guys here, and these are called primary follicles. And in the primary follicles, the layers of granulosa cells and the oocyte, the egg, start to be separated by this other layer that starts to form between them. That's called the zona pellucida, and I'll draw it here in light blue. And even though the egg I've drawn in blue, there's still a layer of zona pellucida, even though the egg is originally drawn in blue because I wanted to draw the egg in blue. There's still a layer of zone pellucida around it. Now even though the zona pellucida is there separating the granulosa cells from the actual egg, the granulosa cells can still nourish the egg through gap junctions that go through the zona pellucida and into the egg. Gap junctions are just little passageways from one cell to another cell where they can exchange nutrients or other signals. And actually, through those gap junctions, the granulosa cells send through little chemicals that keep those primary oocytes stuck at that meiosis one stage, 'cause you remember at this point all of these primary oocytes are stuck in meiotic arrest. They're not dividing and reducing their chromosome copy number. So as we develop from our primordial to our primary to our next follicle here, called our pre-antral follicle, and you'll see why it's called that in a minute, the granulosa cells are actually starting to divide and become a lot greater in number. You can see that there's a pretty big difference in granulosa cell number from our primary follicles to our pre-antral follicle here. And remember the granulosa cells are shaded in in purple here. So while the granulosa cells are proliferating, this wall on the outside of the follicle called the theca starts to form. Theca cells have receptors for luteinizing hormone from the anterior pituitary, and when luteinizing hormone, or LH, binds these theca cells, they produce a hormone called androstenedione. And when the thecas get androstenedione, they give it to the granulosa cells, who then convert it to estrogen and release it into the blood. So the blood estrogen levels start to go up at this point. And so that's what these red and blue bits running down the middle of the ovary are, blood vessels, arteries and veins. And if they look a little bit weird to you, or unusual, that's just because they're cut in cross-section as well. Now you might be wondering what an antral refers to, like what you see in the pre-antral follicle and this early antral follicle here. It actually refers to the antrum, which will be formed in the next step. This space here is called an antrum. And the antrum is just basically fluid that's being produced by the granulosa cells. And it's that antrum and the fluid in the antrum that pushes against the edges of the follicle and causes it to expand. Now just so you're aware, during this ovarian cycle, multiple follicles are actually forming. It's not just this one pre-antral follicle, and then this one early antral follicle, and this one mature follicle. You're getting a lot of these happening at one time. But only one of the biggest ones is the one that eventually gets ovulated, because you only ovulate one egg every 28 days. And that one that gets ovulated is called the dominant follicle. So let's just say that what we're seeing here is an example of the dominant follicle's development. Because the rest of the ones that were developing along this pathway sort of degenerate and die off in a process called atresia. So I'll write that at the bottom here. And atresia just means to degenerate. So another note. In the ones that undergo atresia, both the follicle and the eggs they contain die off. And that means that a woman loses anywhere between 15 to 25 eggs per menstrual cycle to atresia, while only one gets ovulated. So you can kind of imagine how you go from two to four million eggs when you were born to having zero after about 35-ish years of ovulation. It's not just that one egg you lose by ovulation. You lose quite a few. So anyway, back to the development of the dominant follicle. It enlarges mostly due to the expanding antrum, as I mentioned earlier. And granulosa cells actually start to form this bit of a mound here that protrudes into the middle of the antrum. This mound of granulosa cells is called the cumulus oophorus. As part of the development of the dominant follicle, the cumulus oophorus and the egg sort of separate together from the wall of the follicle and float around in the middle of the antrum, like a little island. And the follicle increases in size. So the actual follicle is increasing in size as it gets filled with more and more fluid from the granulosa cells. And the granulosa cells are just producing fluid as a by-product of their metabolism and creation of hormones. Eventually this dominant follicle, which at this point is called the mature follicle, it starts to balloon out the side of the ovary, kind of like this. Just starts to push out against the edge of the ovary. And then because the edge of the ovary and the wall of the mature follicle are in such close proximity, enzymes within the follicle break down that common wall between them, and the egg pops out onto the surface of the ovary, because now this wall is broken down. And by the way, an enzyme is a protein that carries out a specific task. The task here is to break down the wall between the mature follicle and the ovary, and that happens on day 14. So it takes day zero to 13 of build up to get to this event. When this happens, some women feel a little bit of pelvic pain. And actually sometimes, by chance, two or more follicles reach maturity, and they all pop out. And that's how you get twins or triplets or quadruplets or octuplets, when they all pop out and get fertilized by different sperm each. Because they're all subsequently swept up into the uterine tubes where sperm can fertilize them. So now you have the egg out here, but what about the old follicle it was in? The follicle actually collapses a little and transforms into a structure called the corpus luteum. And in this transformation the granulosa cells get a lot bigger and start to produce more estrogen, progesterone and that other hormone, inhibin, that we mentioned before. Just briefly, inhibin lowers the amount of FSH, follicle stimulating hormone, that comes from the anterior pituitary. And it does that because follicle stimulating hormone actually propagates this whole process of follicle maturation, as you can imagine from the name. So if you didn't know this before, these are the exact follicles that follicle stimulating hormone refers to. At least in a female. Anyway, if the egg doesn't get fertilized, then the corpus luteum reaches a maximum size in about 10 days. So that's about day 25, which it's probably sitting at in this diagram. And then it degenerates by apoptosis. That's a process that cells use to sort of self-destruct and die off. And here I'm abbreviating corpus luteum as CL, just so you know what I mean. But if the egg is fertilized, i.e., it travels into the uterine tubes and gets fertilized by a sperm, then the corpus luteum persists, I mean it keeps living, because we want it to keep producing estrogen and progesterone. That's because estrogen and progesterone prepare the inner lining of the uterus, that's called the endometrium, for implantation, which would be really handy since we have a fertilized egg now that needs to develop. And that's where it does it, by implanting in the endometrium of the uterus. So just a final note. Ovulation doesn't happen forever. At about age 50 to 51, females undergo something called menopause. First menstrual cycles become less and less regular. In other words, they don't happen every 28 days like they do when you're under the age of 50. And then ultimately, they stop happening entirely. And that cessation of ovulation is called menopause. The main cause of menopause is sometimes referred to as ovarian failure. Basically the ovaries lose the ability to respond to signalling hormones from the brain called gonadotropins. And we know these as LH and FSH. And this happens because most, or all of the follicles and eggs have already gone through that process that we talked about called atresia. In other words, they've degenerated.