Reproductive

Okay, like with any system, we do the anatomy of the tract first before we go into the physiology. And so this is a sagittal view through a mail and particularly through the pelvic region And what we can see is the male reproductive anatomy here or the male reproductive tract. And so you could begin from anywhere you want. I'm just going to begin from the site of where sperm are produced. And so they're produced in these structures right here called testes. So that's just a singular word there. Testis. Testes would be plural. Obviously, there's a pair of those. And inside those, we'll look inside of them and see where sperm's made. But that's where sperm's made. So these are the actual gonads of the male reproductive system. So what are the homologues to that in the female reproductive system? ovaries, right? So we have ovaries in the female reproductive system making what we call follicles but Not a totally correct term, really making oocytes. And here we're making spermatocytes. We're making sperm. Now, once sperm is made in here in the testes, it's going to be dumped into here. This is a coil tube that you can't really see that it's coiled here. But that is called the epididymis. And sperm will move from the top up here, which is called the head of the epididymis, down here to the tail. And that opens up into a muscular tube right here. And that muscular tube is called the vas deferens. How many people have heard of that? So pretty common, right? So that's the vas deferens. And what I mean by muscular tube, if you looked at it histologically. It'd have a little lumen to it. And then it'd have all these like concentric layers of smooth muscle It's just a really massive muscular tube. And obviously it's doing peristaltic contractions. Now, if we follow this vas deferens along here what we see is it's going to open up into the prostate gland. That's this almond shaped structure right here. So it's opening up into the prostate gland, but it's opening up into the prostate gland along with another structure. So we actually have a gland here called the seminal vesicle And that's opening up as well. into the prostate gland. Both of those, the seminal vesicle along with the vas deferens they form this, which is called the ejaculatory duct. So now that's within the prostate gland proper. So seminal vesicles along with the vas deferens form the ejaculatory duct. The ejaculatory duct is going to open up into this which is called the urethra. So here's the urinary bladder up here. And the bladder is opening up into a urethra that actually runs right through the prostate. So we call this the prostatic urethra. So the portion of the urethra that runs through the prostate. Now, I'm sure you've heard of prostate cancer and you've heard of males having problems with potentially urinating and things like that with prostate cancer. And the reason for that is the anatomy. So the unfortunate situation of this anatomy is that when the prostate gland becomes inflamed or cancerous or whatever it may be. Very often what happens is that urethra gets pinched on And it makes it very difficult to urinate. And of course, if you're using any kind of surgery to try to reduce the size of the prostate gland, it's possible to damage the urethra. That could cause incontinence. Which would be the inability to preventing yourself from voiding your urinary bladder. So there's a lot of complications with that particular anatomy. The urethra then is going to open up right here into the base of the penis. And now it's called penile urethra. So it's running through the core of the penis. And then it opens up to the external environment. And then, of course, we have the penis right here. So we'll talk more about the glands. I didn't talk about all of them yet. I did mention the seminal vesicles and the prostate gland. I guess I'll just mention really quick. there is a set of glands sitting here at the base of the penis that dump fluid into the urethra the penile urethra. They're called the bubble urethral glands. I'll just mention them for now, but we'll talk about them more later. So there's a mnemonic that was given to me a long time ago by the woman that taught me pretty much everything I know. about biology. She said that pretty much you could use seven up to explain the male reproductive tract. And so let's try to do that with the top hat question. All right. Well, at least you didn't choose the ones that I purposely misspelled. So I just try to come up with other E's. So I spelled urethra wrong. inured or wrong. So yeah, it would be ejaculatory duct. Epididymis would be the first one. So if we look at it again really quick. By the way, the S is probably making complete nonsense to you right now. If we look inside the testes, we're going to see these coiled tubes that are called semi-niferous tubules. So that's where the ask comes from. And then epididymis is your E. V is your vas deferens. E is your ejaculatory duct. What's N? What's N always? Nothing, right? And then you would be urethra, P would be penis. So it kind of works for the tract. So now let's go inside the testes or the testicles and take a look at what they're made up of. So these are paired gonads and they're suspended in an outpouching of the peritoneal cavity. So actually, sorry, your testes develop high up by your kidneys They develop way up here. And they go through a process where we say they descend. So the testes are going to descend way down here But they develop way up by the kidneys early on in development. So they go through this descending process. And then what happens is there's an outpouching of the abdominal cavity that forms just in front of the body. Which is going to be the scrotum and then that's where they end up lying. Now, what they take with them when they come down from up there by the kidneys is they take some peritoneal membrane with them. And so now they actually have a visceral parietal peritoneal membrane as well, but we call that tunica vaginalis. For whatever reason. So tunica vaginalis is the remnant of the peritoneal membrane And there's a visceral tunica vaginalis and a parietal one. And as you probably guessed, there's serous fluid in the middle. And it serves the same functions here as it did in the lungs, heart, things like that. So again, tunica vaginalis is nothing more than basically peritoneal membrane, visceral and parietal. So the testes themselves are divided in these testicular lobules. There's a lobule there's a lobule another one here. And each lobule, if you were to look at one of these triangular-like structures. First of all, they're all separated by a little bit of loose connective tissue. And then out here, there's some dense connective tissue They call that a tunica albinia. But inside each one of these is about one to four blindly ending tubes. And we call those seminiferous tubules. And what do we mean by blindly ending tubes is this is where they begin. And that's why it's a good place to begin with the male reproductive Because these tubules begin here, just like how lymphatic vessels begin in the periphery of the body. These seminiferous tubules begin here. So you might just find Here's one of these triangular organizations. You might just find one tube. that again begins And just sort of does this. And then goes out that direction. There's like one to four of them that you find in each lobby. So again, seminiferous tubules. They're encased, the testes that is, by a musculocutaneous pouch. Here it is pretty much from here to here. And that is called the scrotum. So again, musculocutaneous, that means there's skin and muscle. So on the outside, indeed, there's skin And again, it's an outpouching of the abdominal cavity. And then we actually have just visceral to that some dartos muscle. So the dartos muscle is a smooth muscle. So this is not volitionally controlled. And there's a little bit of connective tissue beneath that. this fascia that is the rest of the scrotum. Now, you may look at this and say, well, I see another layer of muscle a little bit deeper than that called a cremaster muscle, that's actually not part of the scrotum technically. So that's more intimately connected to the testes per se. Now, it's a little bit further away, obviously, because it's separated by serous fluid, but it's not part of the scrotum. We consider it part of something called the spermatic cord And I'll show you that a little bit later. Now, there's a lot of vasculature here, so the testes are perfused by the testicular artery. And then they're actually drained by a bunch of veins which we call a plexus. We know a plexus is a network of something And we call this the Pampiniform plexus of veins. So there's like one artery coming in and there's like a bunch of veins coming out And that's a really important setup. Looks like this here. Here's testicular artery. And look at that artery. It's kind of like coiled up. And look at the massive blue veins going like this. And what that sets up people is something called a countercurrent heat exchanger. So that means as your blood is coming into the testes, it's warm. But there's an enormous surface area of veins with blood running in the opposite direction. all these little blue lines are veins. And so what's happening is as blood is coming into the testes, heat is leaving out of the testicular artery into those veins and going right back out So that means that the blood that's actually coming to the testes has a lower temperature And that's really important because the testes have to be about two degrees cooler in the body so that you can properly form sperm. there has to be a lower temperature there. So why is it the testes have a two degree lower test? They're about 35 degrees C instead of 37. So what is the reason why normally they sit at around two degrees lower? Two. One. They're in an outpouching of the abdominal cavity. So they're a little bit standoff from the abdominal cavity. So they have a little bit less heat as if they were inside the body per se. Even though they are inside the body but you know, you know what I mean? So they're in an outpouching. Second thing is this, the countercurrent heat exchange mechanism. So these two reasons are why you're about 35 degrees C. Now, what we'll talk about in a minute is how we can regulate the temperature of the testes But that has nothing to do with the two degrees C per se. It has to do with us keeping it around two degrees But why is it at basal conditions two degrees lower? two degrees lower because of these two mechanisms. So here's how we regulate that temperature to keep it. At 35. So dartos muscle, that smooth muscle, and the cremaster muscle contraction. So the cremaster muscle is both smooth and skeletal muscle Probably most of it is skeletal muscle. And it regulates testicular temperature. So here's how that looks. Now you can see the scrotum here And this is chromaster muscle right here. So you can see how it's a little bit further detached from the scrotum. So it's not really part of it. And we call this cord of tissue here, the spermatic cord. It's got muscle, it's got blood vessels, connective tissue, stuff like that. So that's what the chromaster muscle is part of. But that's largely skeletal muscle Darthos muscle is smooth muscle. Which means that the chromaster muscle is controlled volitionally But it can also be controlled in a reflex fashion as well. And the smooth muscle of the dartos is obviously only controlled autonomically. Now, what you can see on this slide before we move on is something really cool. really nice Pampiniform plexus of veins running countercurrent to the testicular artery picking up that heat that would normally go to the testes, but it's not. So the lower temperature is required for the process of sperm development that is called spermatogenesis. So if we decrease the ambient temperature in the environment, then what happens is the dartos muscle will contract reflexively. And that smooth muscle here on the outside of the testes which is just beneath the skin of the scrotum. When it contracts, the scrotum is going to shrivel So it's sort of like the appearance of like a grape So you got these convolutions And when it shrinks up like that or shrivels up like that, what that does is it decreases the surface area for heat loss. Rather, if the testes were expanded, there'd be much more surface area were he to be lost. So there's less surface area for heat to be lost. So that's one mechanism when it's cold. To prevent heat loss and keep the testes around 35 degrees C, is the scrotum sort of shrinkles up and creates these convolutions that reduces surface area for loss. Now, remember when we talked about the stomach, we said that the stomach had these convolutions called rugi. So these kind of look like rugi, but we said that if we fill the stomach with fluid, for example. then the rugi would go away because we had this massive increase in surface area, right? So you can imagine now in a warm environment that these convolutions on the surface of the testes are going to go away as well as they expand to increase heat loss. Now, also when the temperature is down, the chromaster muscle will contract and that'll contract autonomically. By the way, it doesn't have to be smooth muscle. to contract autonomically as well. So it could be reflexive contraction of skeletal muscle. And what happens to the chromassor muscle is it contracts like this And what happens to that is it draws the testes up closer to the abdomen. So basically, the reason why I say that, even though there's a double arrow here, you could say, well. It can go in either direction. Really, it goes in this direction Because really the skeletal muscle inserts on the connective tissue of the testes. And it originates in your oblique muscles. So your abdominal oblique muscles is where the cremaster muscle originates it inserts in the connective tissue that surrounds the testes And so it's kind of like origins insertions with bone right it's very much the same, but it's just not bone, right? It's muscle to connective tissue. It's kind of like thinking, you know, what's the insertion of the muscle of your tongue? So the origin of the muscle of your tongue is the hyoid bone what's the insertion. just the connective tissue in your tongue. So that's how this works here. So now you're drawing the testes up closer to the body and they're picking up heat off the abdomen. And that is keeping the temperature increased. All right. Questions on this? So let's look at these seminiferous tubules. Again, highly convoluted tubules They're about 400 meters long if you were to stretch them out end to end, including both testes. Which is like, I don't know, like four football fields long or something like that. So really, really, really long super coil tubes. And here's how they look histologically. So this is a nice semi-niferous tubule here, and you would just have to imagine, because this is what it really looks like, something like this And someone just did a cut through it like that And so you see that circle there. You see that circle there? And you see that circle there. You just have to imagine what tube is coming out and coming back into another tube. So that's what they look like. Now, they look very cellular, hopefully you appreciate. All these black dots are nuclei of cells What's interesting about this is this is not like an epithelium. You would think maybe it's a stratified epithelium or something like that. This is a bunch of developing sperm cells So we call these spermatogenic cells. So these are all sperm cells in various stages of development. And beginning here. the most primitive And all the way down to here, mature sperm. So actually all these little wispy things that you see here in the lumen on the seminiferous tubules, those are all sperm tails. So once the sperms mature, it's facing to where its tails are just kind of like pointing towards the lumen of the tubule. Now, what's also here in the wall of the seminiferous tubule are these cells that kind of look like this. And you can't really see them on this image. You can't see them at all. They're called Sertoli cells. And these Sertoli cells are these big, huge cells that actually traverse the entire wall of the seminiferous tubule and there's support cells their nerve cells. So they're nursing these developing sperm cells. We'll talk a lot about them in a little bit. Now, additionally, what we have is we have some cells hanging out here in the interstitial spaces that are not part of the actual tubules And we call these cells the interstitial cells of Leydig. Sometimes people just call them latex cells. those salespeople make sperm. Sorry, testosterone. Those cells make testosterone. So there's some loose connective tissue there, vasculature And then the latex cells. Now with this image here, you can see it a lot nicer. You can see these huge developing sperm cells here And they're maturing and maturing. And now you can see nice sperm head here And some tails facing into the lumen. What's really cool about this image If someone did a particular stain so they could pick up cytoskeleton And what they picked up is a Sertoli cell. So that's their totally cell is a huge cell that looks sort of like this. Here's its nucleus. So that's their Toli cell spans the entire wall pretty much the seminiferous tubule and again there's a bunch of those. Here's another Sertoli cell here. they're helping these cells out. both nutritionally and nutritionally and mechanically supporting these cells. Questions on those? is the histology cool? Not really. Yeah, go ahead. It is. So the late Excels, the question is, are they stimulated by luteinizing hormone to make testosterone? Yes. And by the way, we'll get there in a second, but what's stimulating these cells? to actually mature into sperm, develop and mature. follicle stimulating hormone. Now, that might not make any sense to you because these are not follicles but that's named after what it does in the female body But it does the same thing in the male body. It stimulates sperm maturation here. It stimulates follicle maturation in women. Okay, so Tolle cells, again, here's what they look like. They're in yellow. So here we have a portion of a seminiferous tubule let me trace the boundary of one Sertoliso. the plasma membrane of it that is. So that's one Sertoli cell. They align, you know, pretty much the entire wall. of the seminephrase tubule. Of course, there's spaces between them or there's developing sperm cells. Now, here's another plasma membrane of a neighboring Sertoli cell. And look at here right there They form tight junctions with each other. Nowhere else but right there. By doing that, they separate the wall of the seminiferous tubule into two compartments. So because there's tight junctions here and here. there's one compartment up here we call the ad luminal compartment And then there's another compartment down here we call the basal compartment. So here's the basal compartment right here. That's it. And everything else up there closer to the lumen, which makes sense, is the ad luminal compartment. So in the basal compartment, what we find is spermatogonia. Spermatogonia are the diploid germ cells that males are born with. So males are born with these cells that are diploid that are going to give rise eventually to haploid sperm cells. And those cells are there in the basal compartment separated from the ad luminal compartment by tight junctions. Now, those diploid germ cells are going to do two things. One is they're going to clone. So when this cell wants to start making some sperm cells, what it's going to do is it's going to make a clone of itself. One clone is going to stay behind. And the other one's going to go this way and become a primary spermatocyte. than a secondary spermatocyte, then a spermatid, than a true spermatozoan. So you keep the clone around. And this is why males are fertile until pretty much the end of their life, a male could tend to technically procreate at any stage of their life. After puberty because still, you know, in the 70s and the 80s, they're still making sperm because they have these diploid germ cells. Women, unfortunately, are not born with diploid germ cells. So these diploid germ cells that women have oligonia. So I guess I should take that back. They are born with them. But they're already in a division of meiosis. So they've already gone into meiosis by the time you're born. with males, they haven't even started meiosis yet. So there's a big difference. Once they're already in meiosis and they've already started to divide. That's really part of the biological clock we speak about with women. And it's more complex than that, and we'll talk about that. But that's not the case with males. So these are completely undifferentiated germ cells. Now, you might say to yourself, why do we have these tight junctions here to separate the spermatogonia from the rest of the cells? Well, here's the deal. This cell here, when it clones itself and then this one decides it wants to become sperm cells. Well, it's going to double its dna And then when it doubles its DNA during prophase, there's going to be some chiasmata that form. What are those? Are they teaching us in 161? Or did they put it into 162? Or what is the second lecture class? 171? Yeah. So did they teach you in 161? What'd you have? Oh, AP Bio. All right. So they're not teaching that 161? Didn't show you chromosomes. And then there's some crossing over between DNA here and here. 162? All right. So there's some crossing over going there. And as a result of that, we have some different gene expression now that's happening in these cells Sorry. These cells then what's happening in these cells So as a result of that, these cells are producing some antigens that these cells don't. And as a result of that, that means that there's some foreign things here that if your body recognized your blood's down here And antibodies could attack these cells and kill them. So what happens is we create what we call blood testes barrier we create this blood test this barrier so that this Okay, in the basal compartment are the germ cells we're born with, so they're not going to be attacked. But now these developing cells that are genetically a little bit different and expressing different antigens they're not going to be attacked by the immune system of the host. Now, you might ask, well, once this cell divides into another cell. And then becomes a primary spermatocyte, then how does it get into here past the tight junction? It's kind of an interesting phenomenon. The tight junctions are breaking and forming actually between not only Sertoli cells, but Sertoli cells and primary spermatocytes. until that cell actually gets into the ad luminal compartment. So really interesting. So the blood test as barrier is actually maintained during that process. So what are the Sertoli cells doing here? So they're physically and nutritionally supporting these developing germ cells. So physically, I think you can see that from the image. Nutritionally, they're actually giving them food. They're giving them like fatty acids. They're giving them amino acids. They're giving them fructose. So that's like some sperm food that they're giving them. They produce and secrete a luminal fluid. So Sertoli cells will secrete a fluid into the lumen. that these sperm can be dissolved in so that they can float around. And by the way, they need to float around in something because they're not modal at this stage. Their tails ain't beating and stuff like that. What's also produced by these Sertoli cells is androgen binding protein, which is a really important protein Because what it binds is testosterone. And what it does is it holds testosterone here in very high concentration. like hundreds of times higher than in your normal circulation. And the reason that's important is because you need high levels of testosterone for spermatogenesis to take place. So this thing binds it and holds it there in high concentration. So even though Leydig cells are cranking out testosterone into your body It's always at a very higher concentration. in the testes than anywhere else in the body. They also produce a really cool substance called anti-mullerian hormone And sometimes it's called MIS, which is mullerian inhibitory substance. Either way you like it. mullerian inhibitory substance or anti-mullerian hormone. People, quite frankly, this is the reason why a male becomes a male and not a female. I mean, a single hormone. It's a little more complex than that, but it's almost like as simple as this. So what I'm saying is basically saying the default human being, and I told you earlier this semester when we get to repro I would try to explain to you why women are dominant to men. Because basically the default program of a human being is a female. And so when females develop, they form these things that are called mullerian ducts. And the mullerian ducks give rise to the female reproductive system. to the uterus, the vagina, the ovaries, stuff like that. When an organism is developing and because they have a Y chromosome. they produce this. that causes the regression of the malarian ducts And then the development of the wolfian ducks. So it's like the default program is like the default female, but that'll only be stopped if there's a Y chromosome that produces mullerian inhibitory substance. that causes those malarian ducts to regress and the wolfian ducts to develop into the male reproductive tract. Is that good evidence? I think so. But it's not that simple, but it's pretty cool. And then the production of inhibin. So Tully cells crank out inhibin. That's going to regulate FSH levels. And we'll talk about that. later. So obviously Sertoli cells are extraordinarily important. Think of them as nerve cells, support cells for developing sperm cells. So here are the spermatogenic cells. Someone said you learned all of this in 162. So let's take a look at it. So we got these diploid germ cells that were born with germ just means sex cell. that males are born with. They're called spermatogonia. So here is a spermatogonium. And then that spermatogonium is going to differentiate into a primary spermatocyte. And then it'll leave a clone. So if the clones left behind, then you can keep making this thing develop into more primary spermatocytes throughout your entire life. And again, if email can't do that. Because they're already developed. myotically and so you can't clone a germ cell because there is no quote unquote germ cell to cologne. So the primary spermatocyte is going to undergo meiosis one where it differentiates into secondary spermatocytes. These are now haploid. And then under meiosis 2, These will become spermatids. all haploid here. And then these will morphologically change into mature sperm that we call spermatozoa. So we call this process of the spermatogonium differentiating into primary spermatocytes spermatocytogenesis. And we call the development of spermatids into mature sperm spermiogenesis. So how many? How many sperm do males produce? Just millions and millions and millions literally Like a day just like a day. millions and millions and millions of cells. Okay. Let's do a question on this or two. 50, 60 answers and I wouldn't even have read it by now. All right, let's see what they're teaching over there. Hey, pretty good. So these cells, the ones at the top there. They are diploid. So if you take a look at this particular cell here. Let's just say that chromosome number one is the big chromosome. And chromosome number two is the small chromosome. So chromosome number one, let's say mom is red and dad's blue. The difference here between this cell and the spermatogonium is chromosome number one from mom is doubled. chromosome number one from dad is doubled. Same thing with chromosome number two. So if that's the case. that those are doubled. then that means that you have that 46 chromosomes. instead of 23. You have 92 chromatids because each one of those individual sticks has its own centromere. And then it's diploid. So it's 2n. Does that make sense? A lot of you got that correct. And actually, I'm surprised. Because that stuff's kind of challenging. Well, let's keep going. So now we're looking at anaphase II. So third image down. Oh, my. Yeah, so check it out. It doesn't change, right? It's still one cell. That one cell still contains the same complement as DNA as the first one. So let's go on. the top here are the same ones at the bottom of that last figure you looked at. So if it says prophase two, we're in meiosis two. That last figure was meiosis one. What do you think the answer is? I think you're right. Nice. So good job. So if you take a look at one of these cells at the top now. one of these cells has got chromosome number one from mom, but the other one's got chromosome one from dad, right? So at this particular stage at this particular stage has to be haploid, correct? So there may be another one. Why not? The better you guys do, the more likelihood I'm putting it on the exam. If the percentages were like in the 30s or 40s, but you guys understand this really well. It's worth examining you, Your Honor. I mean, it's like free points, right? So don't put it on the exam. By the way, I wasn't going to anyways, just having some fun with this. I'd have to teach this stuff to put it on the exam. I'm just throwing questions at you. So what are we looking at here? We're looking at anaphase two. So if you take a look at these cells here. So basically we can go back to a metaphase II cell. If we look at a metaphase II cell. Not really much different than a prophase II cell. But in the anaphase II cell, now the chromosomes have actually separated And each chromosome was made up of two individual chromatids. So now there are no chromatids. their individual chromosomes when you look at anaphase II. And on the right here, you got chromosome number one from mom And you got chromosome number two from dad down there, and the other cell has the opposite complement. So as a result. you have the full Chrome. Actually, it's 23, wouldn't it be Yeah, so it should be 23. It should be 23 0N. So the cells are haploid. Because they don't have the full genetic complement, each individual cell, but they have zero chromatids. These are full-blown chromosomes now. And then it would begin. So, correct. Should be 230N. So it should be D. Which is even worse. So. Does that make sense? Can you see how that anaphase II cell is haploid? I mean, it has to be haploid, right? Because it only has this one on the right only has chromosome number one from mom. The one on the left has chromosome number one from dad. So it's got to be haploid, right? But when those chromosomes separate, when you have a chromosome that's paired, those are called two chromatids that make up that one chromosome. Technically, each centromere means you have a chromatid, and there's two centromeres there. When that splits and you have individual sticks They have their own centromeres. Those are now considered individual chromosomes. So now chromatids don't exist. None of that will be on the exam. You like that? This will, though. Some minor stuff about this. Okay, let's talk about genital ducts. We have ducks that are found within the genitals per se. And then we have the ones that are found outside So we say intratesticular ducts. These ones are really germane to the testicles themselves. And then extratesticular outside of the testicle. So of course, in terms of intratesticular ducts we have Ease. These are called tubuli recti. So that's first what the semi-niferous tubules open up into. Basically, they're transporting sperm from The seminiferous tubules to this little labyrinth here that's called the reedy testis. And so the reedy testis is going to collect and transport sperm to here these are called the efferent ducts And what they're going to do is they're going to reabsorb these ducts The Satoly cell secretions. So pretty much everything that was secreted by the Sertoli cells, all that fluid is going to be reabsorbed here by these tubules. And that's going to concentrate and compact the sperm And then in terms of extra testicular ducts, meaning not within the testes per se. Now we have… the epididymis. So there's the head of the epididymis here And this is where sperm is going to enter now out of these efferent tubes. And a couple things interesting happened here. The sperm actually become fully mature here, meaning this is the first point at which they gain motility. But it's very short-lived because as soon as they gain motility the epididymis secretes glycerophospholine GPC, which is a substance that actually sort of puts these cells in like a coma state. And so in other words, they can't swim anymore. So they've achieved motility. which is a developmental achievement But now basically they're turned into like zombies where they can't do anything But just like go with the flow. They can't swim on their own, nothing like that. So they basically have become what we call incapacitated So they're not modal anymore. They're just going with the flow. whatever the flow may be. And the reason for that is we want these cells to be quiescent. We don't want them to be swimming around in the male reproductive tract because they're going to burn a lot of energy And things like that. So basically it's going to truncate their lifespan. So we don't want them active until actually they're in the female reproductive tract. And that's what's going to happen. So then here at the tail of the epididymis, then you open up into the vas deferens, this very muscular tube. And by the way, the epididymis is quite muscular as well. And this is going to propel sperm all the way up this tube against gravity and eventually into your ejaculatory ducts. So the ejaculatory ducts, again, are these really short tubes. What else opens up into an ejaculatory duct? Close enough. Seminal vesicles. So seminal vesicles also open up into that. And then they both, these two ejaculatory ducts, are going to open up into your prostatic urethra. Sorry, it'll be a single ejaculatory duct, and I'll show you that in a second. So here again, testes imagining seminiferous tubules imagine the short tubules, imagine the reedy testis, the efferent tubes Here's head of epididymis, here's tail of epididymis, there's vas deferens going all the way up here peristaltic contractions, moving the sperm. And right here is the ampulla of the vas deferens. It's kind of like a dilated muscular sac. And that opens up here into this ejaculatory duct and so does this gland the seminal vesicle. So now we have an ejaculatory duct there. But really, there's only one ejaculatory duct. If you look posteriorly. You can see here's one vas deferens. Here's another. one seminal vesicle, here's another they all form into one ejaculatory duct. And that ejaculatory duct is going to fuse with the prostatic urethra. So we have right at the base of the prostate Those two are going to fuse together. So initially, you're going to dump seminal fluid into prostatic urethra. pretty much right at the base of the penis and then into the penile urethra. So seminal vesicles, once again, let's look at the glands really quick. Here's your seminal vesicles. Nice image of them here. One right here in a sagittal view This is prostate gland and this is bulbul urethral gland. So let's talk about what they do. Seminal vesicle glands that join the vas deferens, sometimes called ductus deferens, by the way Either way is fine. I prefer vas deferens, but That's just me. So just above the prostate to form the ejaculatory duct. They produce this fructose rich seminal fluid so again feeding these sperm cells as they're hanging out in these tubes. And they also secrete the seminal vesicles cementagellins. And cementagellins are proteins that cause semen to coagulate in the male tubular system. Now, it causes the semen to coagulate because Again, we're trying to make these cells quiescent. which is not very active. We're trying to concentrate them And as a matter of fact, what we want them to do by sort of coagulating them is we want them to kind of be like a sticky glob. And the reason for that is when a man ejaculates, you want that sticky glob to stick to the cervix. So that's the whole point of making or producing cement and gelens to make this like sticky like substance that will I potentially stick to the cervix. in the female reproductive tract. So 70% of seminal volume comes from these. Think about that. prostate gland is much larger But the vast majority of the volume of seminal fluid actually comes from seminal vesicles. So the prostate gland is really an aggregate gland. It's many exocrine glands together. And again, dumps into the urethra. It produces an alkaline rich buffer-rich seminal fluid. And then also produces this substance here called prostate-specific antigen And this is a marker of prostate cancer. So people that have high levels of PSA may be indicative of prostate cancer, something they screen for. Now, PSA is really interesting because really what it is is a protease or a series of proteases. And that liquefies semen. Really what it does is it breaks this stuff up. And it's kind of like released in a time release fashion, if you will, kind of like how some medications are designed to work in a time release fashion. So what happens is a male ejaculates and once the semen gets into the female reproductive tract. that's when PSA is most active. And that's when it liquefies the cementagellins and then it breaks up the sperm, makes them very loose, freely swimming. And now they can swim up in the uterus. So you try to get them coagulated with semenogen so that they stick. And then you want to liquefy that semen so now the sperm can freely swim in the female reproductive tract. And one of the reasons that the PSA becomes active is the vagina is an acidic environment. And that's something that favors the activation of PSA. unlike the prostate secreting this alkaline substance in the male reproductive tract. So about 30% of seminal fluid comes from the prostate gland. So that's interesting. You're 100% of seminal fluid But we still have some glands. We have the bulb urethral glands, sometimes called the cowper's glands. So what are they doing? So they secrete this thick viscous fluid that's thought to cleanse and lubricate the urethra Now, the reason you'd want to cleanse it is because in the male reproductive system, they're sharing their urethra with the urinary system. So you might want to cleanse some urine out of there before you put semen into there. And so there is a pre-ejaculatory fluid that is secreted So prior to emission and ejaculation, this pre-ejaculatory fluid is released. It's not part of semen per se. Because it's released prior to that. And remember, the bulbous urethral glands are right at the base of the penis. So when they're squeezing and emptying, they're just dumping fluid right into here. to sort of lubricate and cleanse the penile urethra. prior to ejaculation and emission. Questions on that? Okay, let's look at the penis. Is the male copulatory organ. It contains three columns of erectile tissue, which is pretty interesting. If you take a look at it, you can see this is one column here. Another column here and the third one down here. This is the dorsal surface of the penis, which would be this surface. The bottom surface is the ventral surface, which is down here. So two columns on the dorsal surface, they're called the corpora cavernosa Singular would be a corpus cavernosum And then there's one corpus spongiosum on the ventral sinus of this ventral surface that is of the penis. Now, what these are are basically vascular spaces So remember when we talked about the heart, we said in the back of the heart there's this coronary sinus. So this dilated vascular space where there's a collection of blood. That's the penis, these spongy erectile columns, all these cavernous vascular spaces. line by continuous endothelium all can potentially become filled with blood. So it's what we call spongy erectile tissue means it can become engorged with blood. or not, one or the other. Now down here is the corpus spongiosum. There's your penile urethra right there. So the urethra doesn't run through the center of the penis. It actually favors towards the ventral surface. Now, in terms of an erection, what's responsible for it is increasing blood flow here. If you increase blood flow here and then you fill these spaces with blood, that's what causes an erection. If you remove the blood from there, that's what causes a penis to become flaccid. Now, these two primarily control erection a penis, the corpus spongiosum does a little bit, but you can see there's much more vascular tissue in the corpora cavernosa. Respectively. Okay. Is that cool histology? Not really. Okay. All right. So let's talk about erection. So during the flaccid state, there's an increase in sympathetic nerve activity, which decreases blood flow to the penis. So check this out here. There's what we call an arteriovenous anastomosis. It's kind of like when we talked about skin temperature regulation. We said that if it's warm out, let's just talk about today, if it's cold outside. what we would do is imagine this is the surface of your skin right here And if it's cold outside, what we would do is I don't know if that's a good yeah let's say it's here's the surface of your skin sorry If it's cold outside, which it is today, we want to keep blood closer to the core of the body. So what we would do is vasoconstrict his blood vessel more blood will go this way And just keep going by the skin, right? Let me take that back. It's cold outside today, we would want to vasodilate that blood vessel. bring more blood into this vascular space here. Oh, man, I'm way off. Sorry. Here's your skin. It's cold outside. Do we want a vasoconstrictor vasodilate? help your old prof out. What are you doing today? Vasoconstricting or dilating outside? Thank you. So the image is appropriate. If we vasoconstrict here and here, we're going to keep blood away from the surface of the skin so we don't radiate our heat away. How do we keep it away? If we vasoconstrict here, then less blood will go here. more will just cruise by and stay in the core of our body. So this is analogous to that. So if you want the penis to be flaccid. then you vasoconstrict blood supply to the penis. less blood here in the corpora cavernosa then they won't become engorged with blood and the penis won't become erect. And that blood will just shunt past and keep going through the circulatory system. So that's why we call it an AV shunt. You're shunting from an artery to a vein. and you're shunting away from the vascular spaces in the penis. So that's flaccid state there, increase in sympathetic nerve activity. Now, during the Iraq state So what's going to provoke this would be sensory excitation and or coitus, which would be intercourse. there's a decrease in sympathetic nerve activity and a concomitant increase in parasympathetic nerve activity And now you know what happens with parasympathetic we vasodilate. via nitric oxide. And now more blood is going to the vascular spaces of the penis than in that shunt. So less blood's going that way. And now the penis is becoming engorged with blood and it's becoming erect. So here's kind of like a flow diagram of this process here. So we have some descending pathways that are coming down. So thoughts, emotions, sensory input, smell, things like that. can all influence blood flow to the penis. So can input from the mechanoreceptors in the penis. The penis is loaded with Pacinian corpuscles. absolutely loaded with Pacinian corpusils. And so increase in activity of neurons release nitric oxide And again, we get the vasodilation. of the artery bringing blood to the penis, dilation, increased blood flow, we get erection. It's something that's kind of cool is when blood's filling in these spaces. What it does is it kind of compresses on the vein that lets blood out. And that is what's responsible for maintenance. of erection. So maintenance of erection is that compression of that vein which makes it difficult for blood to drain out. which sustains any erection. Questions on notes. Okay, so we talked about this before. So before I go through any of it, I'll just ask you a top hat question on it. We may have talked about it like more than once as well. So just tell me the mechanism of Viagra or Cialis. cyclic GMP inhibitors, right? So we want to keep cyclic GMP levels elevated. Let's take a look. Acetylcholine binds to muscarinic receptors on endothelial cells lining blood vessels. activates calcium calmodulin complex. activates nitric oxide synthase. So now you make nitric oxide diffuses into the smooth muscle cells this way And then nitric oxide is going to stimulate guanylocyclase to convert GTP to cyclic GMP. So you had that part, right? in that cyclic GMP is going to cause muscle relaxation. So if you want to obtain an erection and sustain an erection. You need to keep cyclic GMP levels elevated. The problem is, is there is a compound or a chemical that is, that is called pd that's constantly breaking cyclic GMP down to GMP. You want to stop that. And the way you stop that is with Viagra Cialis. So they inhibit PDE. They keep cyclic GMP levels elevated. That keeps the smooth muscle relaxed that keeps the blood vessel open and keeps blood flow to the penis. So ejaculation, a couple steps to it. The first is emission So movement from semen into the urethra. So there's going to be rhythmic smooth muscle contraction This is going to involve epididymis, vas deferens also seminal vesicles, I've added this to your slide. Prostate gland as well. Prostate gland has some smooth muscle in it, so it'll do some contraction as well. Second step is expulsion. So this is the discharge of semen from the penis. So it's a spinal reflex mediated by penile mechanoreceptors. Again, persinea and corpuscles. And this is going to lead to rhythmic contractions of largely this muscle group here. the bulbous spongiosis muscle Now, there's also pelvic muscle that can be involved and urethral smooth muscle, but this is the big player right here. That's why I have it. italicized. So that's it in red. That red is the bulbous spongiosis muscle largely skeletal muscle But it's controlled by reflexes, kind of like with the diaphragm, right? The diaphragm is not smooth muscle, even though it's sort of like autonomically controlled. Really, it's controlled by pacemaker cells in the brainstem. This muscle is controlled by reflexes at the level of the penis. Okay, so let's talk about the hypothalamus. during the development of the male reproductive system. So there's a maturation process that has to occur. So pre-puberty, we have very little GNRHSPN released. from the pituitary gland Sorry, from the hypothalamus. And as a result, very little LH and FSH. And we have a little bit of a little bit substances that are released from the gonad causing negative feedback. So in other words, not very operative system here. At the initiation of puberty, which in males normally occurs somewhere between 9 and 14 years of age. there starts to be a pulsatile release of GnRH. It's kind of like one to two pulses Sorry, it's a pulse per every one to two hours. Like every one to two hours, there's going to be a surge secretion of GnRH. So you can see the arrow is a little bit larger here. So more GNRH. Arrow's a little larger here, more LH and FSH. But really, the feedback mechanisms are not that strong. And that's really intentional right now. Because we really want to flood the gonads with LH and FSH. So that we can actually get the development of the male reproductive tract. And more specifically, secondary sex characteristics. Now, in the adult, what happens is obviously GnRH secretions are a little bit greater. LH and FSH. Now we have a nice operative feedback mechanism as well so that we're actually maintaining normal hormonal levels. So GNRH stimulates the release of FSH and LH, but they have different roles So here's GNRH from the hypothalamus. And here you can see it's dumped into the portal system. gets into the anterior pituitary, stimulates gonadotrophs And they produce FSH and LH. So what's FSH do? stimulate Sertoli cells What does the tolli cells do? I gave you a laundry list of things they do, right? One of the things at the end of the laundry list was they produce inhibin. So when they produce inhibin, inhibin is the marker for negative feedback. that only influences FSH secretions from gonadotrophs. So if you get too much inhibin being produced, then it means there's overactivity of Sertoli cells. And then we want to reduce the level of FSH. And we do that via an admin. Sir Tolle cells are going to stimulate spermatogenesis. Of course, they're involved in many other things. functionally, nutritionally supporting these developing germ cells. Luteinizing hormone just stimulates latex cells They make testosterone and it stays locally here in a high concentration because of ABP. androgen binding protein. So that's what holds it there in high concentration. Now, by the way, that came from Sertoli cells as well, androgen binding protein. Now, testosterone can negatively feed back It can inhibit FSH and LH at the pituitary. Sorry, not FSH, just LH. And then it can go all the way up and inhibit GnRH at the hypothalamus. Both of those are what? They're both negative feedback, but they're both what? Also, yeah, they're both long loops. Now, once again, follicle stimulating hormone is named after what it does in the female reproductive tract, which we'll talk about next. It stimulates the development of follicles So sort of a misnomer there there What we're talking about here is the development of spermatocytes. which is sperm. In the female reproductive tract, we're talking about development of oocytes. Which is basically eggs. But eggs are surrounded by support cells that are called follicular cells. And that's why we call them follicles. And we'll separate that out when we get there. Okay, so this is male testosterone levels. point of fertilization. And you can see here at puberty, there's a huge exponential surge. of testosterone levels. until they reach the adult levels. And again, puberty somewhere around nine to 14 years old. Now, there is sometimes this surge here. I say sometimes, it always occurs This is sometimes called a mini puberty. So this little mini puberty here is somewhere around three months pregnancy, there's a surge in testosterone in the male reproductive body And that's thought to be involved in the development of the male reproductive tract very early on. I don't think much is known about that, but we know that it does occur. And then it comes back down. And then again, it surges at puberty. And you can see pretty much throughout the lifespan of a male. stays elevated. Now, beyond 50, it's going to start decreasing maybe one 2% of testosterone levels every year. Pretty much. throughout life stays pretty elevated. Certainly enough. to fertilize eggs. So testosterone is the primary male sex hormone responsible for proper development. growth and reproduction of species. So look, muscle, bone, secondary sex characteristics When I talk about them, I'm talking about like facial hair, thickening of vocal cords, things like that. Testosterone is converted into a much more powerful species that's called DHT, dihydrotestosterone. This happens via an enzyme called 5-alpha reductase that's located in the prostate gland. Individuals that have 5-alpha reductase deficiency will have a normal reproductive development And what I mean by that is the reproductive tract But sometimes what happens is their external genitalia are ambiguous. So we have an individual that it's not really clear if they have testes or not or a penis or not. Even though the internal reproductive tract is clearly male. So the proper development of the penis and the testes and things like that is instrumental is instrumentally. dependent on this enzyme right here, 5-alpha reductase converting testosterone to DHT. So DHT is a really important substance for the development of the penis and the testes. Now, high levels of testosterone, we've talked about this before, can be converted to estradiol. And that's actually going to happen in Sertoli cells because they have the enzyme aromatase. So that estrogen can actually be created by Zertoli cells. It's thought to enhance spermatogenesis, so there may be some importance to that. But otherwise, if you have abnormally high levels of testosterone, you wouldn't normally want this to happen. I put an asterisk here because i put an asterisk because Certainly testosterone is involved. and the development of secondary sex characteristics But believe it or not, so are adrenal hormones. like DHEA and androstenedione So they actually have an influence on that even before puberty One thing that's starkly different is the location of the urethra. So when we talked about the penis, which is the male copulatory organ, we said in the ventral surface of the penis in the center of the corpus spongiosum was the urethra. Well, this is the female compulatory organ, the vagina. But the urethra is separate. So it's over here. So there's a urinary bladder. The vagina opens up into the uterus. We've talked a lot about the uterus this semester. And then there's actually two other openings to the uterus And one is on this side to this fallopian tube And the other one would be on the opposite side that's cut away to the other fallopian tube. Now the fallopian tubes, you can see that at the end of them, they're kind of like surrounding ovaries. So we got a pair of ovaries that are suspended here. We'll look at those in detail. Here is the homologue to the penis in a female. So this is the clitoris. It's very analogous. So much so it's homologous, meaning spongy erectile tissue, meaning it becomes engorged with blood during coitus. And it becomes erect, like a penis. And as a matter of fact, if you look at the anatomy of a clitoris. you're so inclined, it actually looks like a smaller version of a penis. When we look at homologous structures a little bit further. The labia minora The homologue is the urethral surface of the penis. And then the labia majora the homologous structure in a male would be scrotum. So all of these are homologous structures here. Okay, so let's look at the ovaries. This is where all the business is. This is the gonads of the female reproductive system. And homologous to testes. in the male reproductive system. So they're located in the pelvic cavity And they're laterally flanking the uterus. So this is a huge ovary right here at least it's a big image of an ovary is what I mean. And you can see that there is a ligament that attaches this thing to the side wall of the uterus. So that is called the suspensory ligament. We'll take a look at that in another image in a little bit. But when you look at the organ itself, when you look at the ovary itself, you can see that it's got a very dark region here It picks up a lot of stain. And then a very pinkish light region here So this stain is called hematoxalin and eosin. You don't have to know it for the exam. It's like the most common stain that's used when people do microscopy. Things that are um Things that have like a lot of DNA, RNA negatively charged they pick up the dark color. So that would be the hematoxylin. Things with a lot less of that. collagen, stuff like that, they pick up eosin pink like color. So again, not for the exam, but what that means for you then is This region right here is very cellular. A lot of cells there. And that's the cortex. of the ovary. So the cortex is very cellular. The medulla is very vascular. It's got a lot of blood supply there, connective tissue, stuff like that. So when we talk about the development of oocytes. We're talking about in the ovarian cortex. We're not talking about in the medulla. Now, this is surrounded by an epithelium that is called a germinal epithelium. And it gets the name germinal because we used to think that all of these developing eggs that are located here they originated from these cells. In other words, we used to believe these were the oligonia. that further differentiated primary oocytes and secondary oocytes. And now we know that's not the case. They're really just a modified visceral peritoneal lining. So they were called germinal epithelia because we thought they were germ cells. We thought they were sex cells, but they're not. So the cortex varies cellular. We can say there's oogenic cells like in the male reproductive system when we said spermatogenic cells. And so these are developing eggs. They're not developing sperm. And again, the medulla is a loose connective tissue that's very vascular as well. So it shouldn't surprise you that greater than 80% of ovarian cancer is in the cortex. It's because those cells there are very mitotically active. And so there's always a risk of cells that are undergoing mitosis. to not being able to stop doing that. In other words, give rise to tumors. Okay, so the cortex contains oogonia. These are the germ cells or the stem cells again homologous to spermatogonia we saw in males. What they are are developing ovarian follicles. And what that means is we have an oocyte that is surrounded by support cells that are called follicular cells. And then around that is some connective tissue cells that we call stroma. So the stroma is like the connective tissue cells. So remember in the male reproductive system, we had these spermatogonia that were diploid germ cells that males were born with. And throughout life, what they do is they clone one of them The clone stays behind so that you always have this diploid spermatogonium But then the other one becomes a primary spermatocyte, then a secondary spermatocyte. And that means males throughout their entire lives, even in their 70s can generate new sperm because that first cell, that spermatogonium is not already divided. It's not differentiated yet. Now, in the female reproductive system that's different And we'll take a look at that in a second. Females are not born with Olegonia per se. And I'll clarify that in a second. Really nice look here at a follicle. So here you can see the connective tissue cells on the outside. These are stromal cells. This is the oocyte right there. So if you want to say, where's the egg, that's it. And at this stage, this would be called a primary oocyte, and we'll talk more about that in a little bit too. Now, surrounded by support These support cells are called In this particular image, what do they call them? follicle cells, which is good. So follicular cells So follicular cells are these nurse or support cells that are surrounding the oocyte. So here's the deal here where it's different than in the male reproductive system. So when we look at this here, we say, well, what are we dealing with? Are we dealing with oligonia or are we dealing with oocytes or are we dealing with follicles? What is it? Well, females are not born with oligonia. I'll explain that in a second. But they do have oocytes. And then males have spermatocytes. But then why do we talk about follicles? We talk about follicles because the oocyte is always surrounded by some support cells. And this… is a follicle. So it's kind of like the same thing to say, hey, this is an oocyte, this is a follicle, but it's not. They're actually very distinct. The oocyte is the cell in the middle And then there's support cells called follicular cells, then that whole thing is called a follicle. So in other words, you got an egg in your follicle. Does that make sense? All right. So we'll do a question on that real quick. Indeed. So it'd be the same thing as Sir Tolle cells. So here's the deal. The Oregonia actually developed… in women when they are embryos. And they actually develop in an extra amniotic sac. So the embryo is located inside the amnion. But there's this little outpouching of that that is called the yolk sac And that's actually where Olagonia develop. They develop in the yolk sac. Which is really bizarre because they're developing here And what they're going to do is they're going to migrate into the embryo and then go into the ovaries that haven't developed yet. and then take up shop in the ovarian cortices. just like crazy bizarre right These cells are migrating and dividing mitotically and meotically And just cruising all the way over into the embryo, taking up shop in the ovarian cortices. So this says mitotically divide. They're also meiotically dividing, migrate to the ovarian cortices. And there's about 7 million total, including both ovaries But at the point of birth. there's only 1 million left. So by the time a woman is born, she has about 1 million of these follicles Or you could say, oh, Agonia. in both ovaries together. So the Oregonia that are present at birth have entered meiosis. and are now referred to as primary oocytes. So I've changed the terminology of this this sentence right here on your slide. The Oagonia president at birth Really, there are no Olagonia present at birth. They've already done a first division of meiosis And so they're called primary oocytes. Remember that when spermatogonia did their first meiotic division, they were called primary spermatocytes. So women are born with primary oocytes. They're not born with oligonia. when a woman's developing in their mother's body, yeah, they have oligonia But by the time they're born, those cells have already divided meiotically and become primary oocytes. Is that clear? So because of that. That's one of the main reasons why women have a biological clock. So they don't have those diploid stem cells that can constantly differentiate into primary oocytes and then secondary and then mature eggs So they're born with all primary oocytes that have already divided meiotically And that means they have a finite number. Does that make sense? One of the major reasons of the biological clock for a woman. So the primary oocytes are surrounded by follicular cells. We call them primordial follicles at this stage So women are born with primordial follicles that contain primary oocytes. Women are not born with oligonia. Men are born with spermatogonia. So we call this the ovarian reserve. Someone can do an ultrasound of your ovaries and they can look at your ovarian cortices. the cortexes, if you will. And they can see how many of these that you have. So this is a good look at this here. This is not an actual image. This is an artist illustration of a histological image, but it looks just like that. These are all primordial follicles. hanging out in the cortex of an ovary. Now that's a little bit more developed one there and we'll talk about that in a little bit. Now, here's the deal. Only 300,000 primordial follicles are present at menarche. So what's manarchy? Anyone know? So it's the point of, yeah, go ahead. Not menopause. It's actually the point of first menstrual flow. So when a woman first has her first period or menstrual flow. That's menarche. At that stage, there's only 300,000 left of the 1 million. And so what's happened to the rest of them is they've undergone follicular atresia, which means they've just degenerated and they've died off. So the reality is by the time a woman is capable of actually conceiving of She's dealing with about 300,000. follicles. So at birth, these primary oocytes, so not only have they already gone into meiosis, they're actually stuck in meiosis. So they were arrested in meiosis. They're frozen in it. And that is another reason for the biological clock. They're stuck in meiosis one. They're suspended in it. Only after puberty or at puberty, when there's a luteinizing hormone surge. does the cell resume meiosis I? complete it and then go into meiosis two and then become a secondary oocyte. So to become a secondary oocyte from a primary oocyte, there has to be puberty. And we'll talk about how that works. And that causes the resumption of meiosis one, the completion of meiosis one. And then the entrance into meiosis two But then again, you get frozen in meiosis too as well. So another reason for this biological clock are the cells are frozen in meiosis. And because they're in this suspended animation state. Sometimes the meiotic machinery doesn't work well and chromosomes don't separate properly and things like that. Now, if you calculate one ovulation for 28 days. roughly the reproductive lifespan of a woman is 30 to 40 years. A woman is dealing with about 450 oocytes in her lifespan. So nothing to worry about, right? I keep telling about these numbers shrinking. You're going from a million now down to 300,000. And really what you're only dealing with is about 450 It's plenty, right? So absolutely plenty. So, Olagonia. in the embryo, they're not in the a child. So we have a primary oocyte. And the primary oversight is in meiosis I. And so we have all of these at birth. So the primary oocyte surrounded by the follicular cells we call a primordial follicle. And then roughly at the age of 12, all the way up to around the age of 40 and certainly beyond 40 as well. What can happen is we can get these luteinizing hormone surges And what happens is the cell will And the cell meaning the primary oocyte it'll resume meiosis 1. It'll complete meiosis I. And then it'll actually go into meiosis II. And then it'll get stuck there again. What gets it out of meiosis too is when the sperm fertilizes it. So the only way it gets out of meiosis II is when the sperm meets the egg. Well, what I mean by get out of meiosis too is complete it. Okay, so we talked about the hypothalamic maturation during life in the male. In the female, it's similar in terms of how we have the low GnRH and the low LHFSH And not a very operative negative feedback mechanism during pre-puberty. And we can see now GNRH is starting to pulse more LHFSH. Not really much feedback there. And the reason for that is we want a lot of LH and FSH And this initiates puberty here, and really it's around a range of eight. to 13 years old. So as early as eight years old, a woman can reach puberty. What's interesting about that is if we look at the 20th century, that number 13. And if we look at the 19th century, it was like 17. So it's going down and down and down and down. Now, there's a couple of reasons for that. Probably one of the main reasons for it this childhood obesity. So childhood obesity is drawing this They're dragging this number down to a lower level. And you'll see why in a second. So now we get this pulsatile release of GnRH. And now we have a fully operative system with negative feedback as well. So here's what's cool. It's believed that a woman's body requires about 12% adiposity to initiate puberty. And so when you have about 12% body fat, there's leptin that's released from the adipose cells. And what it does is it stimulates these kiss peptin neurons. When it stimulates cispeptin neurons, they stimulate GNRH neurons. So they secrete gnrh And now we get this pulsatile release of FSH and LH. And then they do their respective things that we'll talk about shortly. So one of the major initiators of puberty is that you have enough adipose in your body, which means that your body has an appropriate nutritional state to actually carry another organism within it. Now, if you look at gymnasts Very often they're short in stature And very often they have delayed puberty. And the reason for that is because of this. They actually have really low body fat. And they have a really low nutritional state as well. And what I mean by that is probably a low caloric intake. I'm not saying they don't have like good protein sources, stuff like So low caloric intake, really low body fat And so what happens is not only do they have delayed puberty. But with puberty, what comes is a huge growth spurt. And so they lack that as well. So part of the reason why when you look at gymnasts, they're a little bit shorter than their peers is because of this. Now, sometimes what happens is they actually end up with something called this. amenorrhea. So amenorrhea meaning they don't have a menstrual flow. Or at least this is significantly delayed And obviously, if their puberty is delayed, then this is going to be delayed as But sometimes they have this altogether. So they don't have menses. menstrual flows. Okay, let's look at these follicles that develop. in the ovaries. So this is the primordial follicle here. And all of these collectively make up a woman's ovarian reserve. The primordial follicle will develop into a primary follicle which becomes a secondary follicle which will further mature into a tertiary follicle which would further mature. We would like to say quaternary, but you guys don't like that word. So we don't use it. We just say mature follicle or a graphene follicle. So mature graphene focal. And those terms are coming up on the right side of the slide. Now, this mature follicle, what it's going to do is it's going to fuse with the surface of the ovarian cortex And the ovarian cortex is going to lose blood supply. So its surface is going to be very weakened And basically your follicle is going to become continuous with your peritoneal cavity. And then you're going to get a release of a release that oocyte into the peritoneal cavity. Now, it's not likely to end up in the peritoneal cavity, but that's technically where it's released in terms of the space. And then here they're showing that Once the follicle is released. Because there is molecular cells surrounding it, so we can still call it a follicle. Once it's released. the graphian follicle becomes a corpus luteum, which is a temporary endocrine gland Now, it's only going to stick around if there's pregnancy So if there's pregnancy, this thing's going to hang around and secrete hormones that actually maintain the uterine lining and things like that. If there's not a pregnancy, then the corpus luteum will degrade into a corpus albicans. We'll take a look at these things. So primordial follicles right here They say that it has granulosa cells. Technically, they're called follicular cells at this stage. And these cells right here, even though they don't look like it, they're squamous. So keep this in mind. The cells that surround oocytes that make up follicles are in general called granulosa cells. But in the primordial follicle the granulosa cells are squamous And we just call them follicular cells. But once they become cuboidal, then we call them granulosa. Why that's the case, I don't know, but that is the case. So when you look at primordial follicles, we'll say, hey, we got follicular cells. When that matures into a primary follicle, a couple things happen. One, those squamous cells become cuboidal. Now they're called granulosa cells. And then also you can see that the oocyte is maturing and getting larger as well. So the egg is getting bigger. So this is then going to mature into a secondary follicle. You can see there's stratification of the granulosa cells. There's several layers of these cuboidal cells now. And the oocyte is further maturing. still primary oocyte at this stage. Secondary follicles become tertiary, the follicles getting bigger You can see there's much more granulosa cells The oocyte is getting bigger. And what you can see is that there's some spaces that are starting to build up. Sometimes you'll see a couple of them here. And these spaces are called antrums. So these little fluid-filled spaces are building up within the follicle between the granulosa cells So sometimes we call these antral follicles. So we can see these little antrums, these little cavities. So we say antral follicles. We'll talk about what's in those spaces in a little bit. Now, lastly, the mature follicle is called the graphene follicle And the graphene follicle this guy's got I just said this guy. this gal. This gal's got a secondary oocyte. So it's a secondary oocyte now. And you can see all of those antrums have fused together into this huge cavity now. And what you can see is that the secondary oocyte with a little bit of granulosa cells only have a little bit of attachment to the rest of the follicle. Eventually, that's going to break off And this is just going to float around freely inside that cavity. And then when this follicle fuses. with the ovarian cortex it opens up then you can just release the oocyte into the peritoneal cavity. Okay, so let's look at some images of this. So this one is a little bit manufactured. The only thing that's not original to this image, this is an actual histological image. is I added this and I added this. Just because I wanted to show you all these follicles here. But these are real images too, nonetheless. So look, this is your ovarian cortex. These are primordial follicles. Now, what you can see is all stages of follicular development here. And it's kind of rare to find that. And that's why I threw a couple screenshots in there of some other follicles. It's kind of rare to find it in one small section like this. This right here is a what? So that's a primary follicle because it's got an oocyte surrounded by single layer of cuboidal granulosa cells about this one. Secondary. Probably another secondary right there. It's a primary starting to become a secondary. You can see you're starting to stratify and a couple layers of cells. This one right here. That's tertiary antral follicle. There's those antrums, those fluid-filled cavities That's a mature follicle right there. That's a graphene follicle. And again, all you have here is that little bit of cells there. These are called cumulus cells. that are attaching this oocyte to the rest of the follicle. And you can actually see there's some fluid building up there too. Once that fluid builds up in those spaces and breaks those cells apart. this thing will just float around inside. that follicular cavity. You can see some nice stromal cells here, these connective tissue cells. surrounding these follicles, all these are connective tissue cells. Is that cool? Oh, I get some nods now. I said that about male histology. You guys are like, eh. Well, I agree with you. This stuff's beautiful. So primordial follicles, 300,000 are present at menarchee. They develop in the absence of FSH. So… In the absence of FSH, so in the absence of puberty. We have the follicle still developing. So there's other signals other cytokines and things like that that are causing these cells to mature at this stage. So again, we got a primary oocyte surrounded by a single layer of squamous cells that we call follicular cells. How nice that is. Squamus. squamous, squamous. Squamas, squamous and there is squamous your primary oocyte. And this one is just It's just an artifact of tissue preparation. when you happen to cut it there, you just don't see the nucleus in that frame of view. Big deal. Primary oocyte is stuck in meiosis I. Cigarette smoking kills follicles. Keep that in mind. So you're dealing with 450. And that's you know, when you start, let's say you start hitting your 40s and you want to have a kid The likelihood of having a kid in your 40s is significantly lower than in your 20s. significantly lower. And if you're smoking, then obviously that's going to make it much worse. So just keep that in mind. It's two questions. What do you think? Bringer likes bees. Yeah. So, hey, metaphase is a good guess And the reason for that is you would think, hey, these chromosomes are aligned on the metaphase plate. And if they're stuck there, then separating these chromosomes could create a problem. So that's a good guess. It's actually prophase. And the reason why that's a problem You have these chromosomes here. Wow. And I probably can't draw this as well. Try to. Yeah, I know it's rough. you got these chromosomes here that are swapping dna They're forming these chiasmata and they're exchanging dna And when these things separate apart, problems can happen with that so being froze in pro phase creates a problem. It also can create a problem later with metaphase. with chromosome separating properly. And so very often what you end up with is if they don't separate properly, something called aneuploidy. So you get an aneuploid cell that doesn't have a normal ploidity. And what I mean by that is it's missing chromosomes or has extra chromosomes, something like that. Okay, primary follicles develop from primordial follicles, again, pre-puberty in the absence of FSH. The primary oocyte is getting bigger. It's hypertrophying. It's secreting some paracrine factors that stimulate those squamous cells that are surrounding it. to actually grow into cuboidal cells and actually stratify into multilaminar layer as well. So now we call them granulosa cells. So this right here is Oh, that's a bummer. want to blow it up. Why can't I do that? I usually can expand my screen. Mr. Prague. a little bit upset by that. Let's try it this way. Here we go. That is the most gorgeous picture I've ever seen in my life. I'm not even joking. Not even joking. So again, I taught histology for 10 years down at Wayne State. When I saw this thing, I lost my mind. That thing is absolutely beautiful. Ladies. If I knew I had that in my body, I'd be proud. I mean, it is. Look at it. So it's a beautiful primary follicle. It's a beautiful primary follicle. Probably starting to transition into secondary Because it's getting a couple layers of these granulosa cells This thing's called a zona pellucida. We'll get back to that later. And then I have a question for you. was that eye that's staring at you? Not that question. Isn't that nice? the way, this is the nucleus here. This is nucleus. Right here. Sorry, take that back. That's Nucleus. That's nucleolus. What's new, Cialis? Other than eventually the name of my firstborn son. Yeah. Very good. Site of ribosomal RNA synthesis, not on the exam but Just pointing that out. By the way, even though this is gorgeous, it's color enhanced, unfortunately. So it's not that pretty in the human body. That's H&E staining there. Okay, so stromal cells organize around primary follicles. They form something called a theca interna, which is a cellular layer. And then a theca externa, which is connective tissue. So take a look at this. Here's your OS site. here's your granulosa cells here And then now you see some stromal cells that are forming like a concentric ring here around the oocyte and granulosa cells Those are theca interna cells. And then out here, the theca externa connective tissue cells. Now, the theca and turnna cells produce androstenedione. We talked about that in the male reproductive system in the adrenal glands. But they only do it in response to luteinizing hormone. So just remember these cells for now. These tika and terna cells will produce androstenedione. Now, what they're going to do, we'll talk about it later. is they're going to take the androxenedione and they're going to dump it to the granulosa cells. They're going to give it to them. The granulosa cells have an enzyme called aromatase. And they're going to convert androstenedione into estrogen. Now, this is estradiol. Estradiol is estrogen. It's the most potent form of estrogen. in the female body. So now you know where estrogen is made in the female body. It's actually made by granulosa cells. It's actually made by follicles. So it's follicles that are creating estrogen And they're dumping it into the spaces around them. And again, they're creating these fluid-filled spaces called antrums. And one of the main things in those antrums is Estrogen. Secondary follicles, to get them, you need FSH, so you need puberty. So FSH stimulates primary follicles to develop into secondary follicles. So again, it's FSH dependent. The primary oocyte is going to further hypertrophy. It's going to get bigger. Granulosa cells are going to stratify even more. even more multi-laminar And then the granulosa cells are going to secrete what we call liquor folliculi. So liquor folliculi, I don't know where the ideology of that is. Or what it is, but what it contains is growth factors two big things, estrogen and progesterone And then remember, we talked about Sertoli cells producing inhibin. Well, granulosa cells secreted as well. And there are nerve cells just like Sertoli cells. Now they're dumped into the ISF surrounding the cells. And again, that'll start accumulating and forming these andromes. So the antrums contain liquor folliculi, which is all this stuff. And then it'll get into your blood and then it'll regulate GnRH and LH and FSH levels as well. So think of your follicles as like little endocrine glands. So these little follicles are endocrine glands. Now, if we want to contrast that then or compare it to the male reproductive system. There's no follicles there, but when you look at the seminiferous tubules remember the tubules where those sperm are developing in the Sertoles cells that are helping outside of the seminiferous tubule and the connective tissue, there's latex cells. And they're cranking out testosterone. So really nice secondary follicle here Sometimes we call it a secondary multilaminar follicle because it's got all these layers of granulosa cells Let's identify some things. or not. I think I do it on another slide, but I'll do it here too. Again, these are your granulosa cells. This is called a zona pellucida, that little pink band We'll talk about that in detail. This is your theca interna. Look for concentric like cells. And then theca externa out here. By the way, none of these images will be on the exam. You won't be examined on any histology. Tertiary follicles are often called antrofollicles. Again, you need FSH for this. Primary oocyte is getting bigger. The feca and granulosa cells are further undergoing hyperplasia. And now they're forming different areas of granulosa cells. One area is called the cumulus oa for us and the other one's called the mural granulosa So really nice antral follicle here, two big antrums. maybe even a third antrum right here. And that contains liquor folliculi, which you known as growth factors, estrogen. progesterone inhibin, things like that. So that's the primary oocyte. Tika interna, Tika externa. We call these cells here. the mural granulosa cells. So look, they're granulosa cells. You know that. But they just have a special name. They're called the mural granulosa cells. So that's the mural granulose cells. This is mural granulosa here as well. The ones that surround the oocyte We call those cumulus cells. So all these are going to be cumulus cells. All that here. And then it's kind of a gray area. It's cumulus here and it's a little bit of mural here. So what immediately surrounds the oocyte, we call those cumulus cells. Now, when you look at the oocyte. and you look at the first layer of cuboidal cells around it, the first layer of granulosa cells. We call that the corona radiata, just a single layer of granulosa cells around it. And those are really important cells that the sperm actually have to penetrate through those cells. to get into the zone of pellucata So that they actually can undergo this acrosomal reaction so that they can fertilize the oocyte. That's pretty much all that stays with the oocyte. Once it's released. So once it's ovulated, pretty much it's just left with I mean, initially when it's ovulated, there's some more granulosa cells. But eventually, by the time the sperm meets it, it just has a corona radiata. And by the way, that corona radiata is doing a couple of really important things. It's structurally supporting. the oocyte, but it's also nutritionally supporting it as well So when we talk about Sertoli cells giving sperm sperm food, well, granulosa cells are giving oocytes oocyte food. They're feeding them and keeping them alive. Now, eventually, all of these fluid-filled cavities are going to just merge into one huge cavity and that's where we're going to get a mature graphene follicle. So here's Zona pellucida in pink. And what this is, is the oocyte secretes a bunch of glycoprotein on the outside of its membrane. So there's a bunch of glycoprotein between the oocyte membrane and the granulosa cells. And there's actually proteins in there that the sperm head is going to actually bind to. We're not going to talk about those but that glycoprotein there is really important for the activation of sperm so that they can fertilize the ovum. And there's just a nice capillary right down there. So at this point, the ovary is functioning as a temporary endocrine gland. cranking out estrogen, it's cranking out progesterone, more so estrogen than progesterone. We'll talk about that in a little bit. So mature graphene follicle, once again, you need FSH. Further, theca and granulosa cell proliferation. That's a beautiful graphene follicle right there. A little bit different staining there. I forget what it is. It's not H&E. I don't remember what it is, but I forget. But anyways, all mural granulosa cells here all cumulus cells. here and all of those antrums have all fused into one huge fluid-filled space and all you got left is that little patch of cumulus cells And that fluid is going to keep accumulating and it's going to break loose these cells And again, that's when that follicle is going to float around. that's when the oocyte that is is going to float around in the middle of the follicle. Secondary oocyte at this stage. So remember, to get a secondary follicle, we need a puberty. So now we have LH and we have FSH. And particularly the LH and of course the FSH as well, is causing indirectly, that primary oocyte to finish meiosis I and then go into meiosis II and get stuck there as well. That's when we call it a secondary oocyte when it's stuck in meiosis II. So what I like about this image is it actually shows you it's starting to detach. So again, further fluid building up here we're going to break this loose. Really nice look at this glycoprotein right here. um and uh Zona pellucido. By the way, there's actually gap junctions between granulosa cells and the oocyte. So there's actually direct communication between these cells. Okay, so let's talk about ovulation. So it's the release of the secondary oocyte. We can call it immature ovum, if you will. from the graphian follicle. So an ovum is an egg, just another word for that. So this results from FSH stimulating fika interna cells to express luteinizing hormone receptors. So remember when we were looking at these follicles Let's go back. And find one here. So what's going to happen is lh is going to stimulate That's not a good image to see it. a good one here. So I'll say this all again, but this is what's happening. LH is going to stimulate PICA internal cells to express luteinizing hormone receptors. Sorry. FSHs. FSH And remember, this is FSH dependent. It's going to stimulate theca interna cells to express luteinizing hormone receptors. Now, luteinizing hormone is present as well. luteinizing hormone will bind to those receptors and it'll tell those theca interna cells to make androstenedione. that androstenedione will be shuttled to the granulosa cells And the granulosa cells with their enzyme aromatase we'll convert that into estrogen. We say estradiol, the most potent form of estrogen. And that's what's building up now. in these interstitial spaces. And that's what is a major component of liquor folliculi. So just wanted to show you that just before I just give you a bunch of gory lines of detail here. So… the release of the secondary oocyte from the graphene follicle results from FSH, stimulating fuca interna cells to express luteinizing hormone receptors. Luteinizing hormone stimulates these cells to produce androgens, specifically androstenedione. granulosa cells convert that to estrogen via aromatase. So this is what's causing a surge now in plasma estrogen in the female body. So again, you got these temporary endocrine glands in the ovaries. They're cranking out estrogen. typically just one at this stage and it's cranking on estrogen and estrogen levels are rising in the blood. The increase in plasma estrogen is going to cause a luteinizing hormone surge by the 14th day. of the menstrual cycle. So what causes the luteinizing hormone surge is a surge in estrogen. So luteinizing hormone surge is actually going to cause ovulation So what stimulates the release of the ovulator Estrogen, what is the ovulator luteinizing hormone. So luteinizing hormone surge is going to cause the secretion of meiosis inducing substance from cumulus cells. Very cool. So the cumulus cells are going to secrete meiosis inducing substance which tells the primary oocyte resume and complete meiosis i and go into meiosis II, And get stuck there as well. And now it's a secondary oocyte. So LH actually tells cumulus cells to do that. The mural granulosa, they loosen up, the ovarian surface loses blood supply. cortex of the ovary loses blood supply. And it starts to degenerate forming what we call a stigma. So it's starting to rupture the surface of the ovarian cortex. And now the follicular antrum becomes continuous with the peritoneum. Ovulation occurs the 14th day. before the beginning of menstruation. Now, the remnant of the graphene follicle will either become a corpus albicans or a corpus luteum. Quite frankly, it will first become a corpus luteum no matter what. But if there's not a pregnancy, it'll degrade into a corpus albicans. There is a pregnancy, it's going to stay around We'll talk about the details of that shortly. So I believe this is a rabbit ovary here. And it's a really cool image because it's actually showing ovulation just in one image. So this is the whole ovary right here. This right here. is a mature follicle. These are all granulosa cells, more specifically the mural granulosa. And look at right here. There's a secondary oocyte. And there's the cumulus cells surrounding it. Look at primordial follicles back here. Immature one there too, probably a primary follicle. Now, if you look around, you don't see really any other follicles. And the reason for that is there's a process that goes on with follicular development that is called dominance. And what happens is when one follicle starts getting ahead of the rest, what it does is it secretes chemicals to cause the other ones to atrophy and degenerate. They undergo follicular atresia. The other reason for it is when you start cranking out a lot of estrogen, that's going to inhibit FSH. So when you got one follicle cranking out estrogen, that tells FSH levels to go down. And what does FSH do? stimulates follicular development. So you're actually halt, follicular, any further follicular development because you got a dominant follicle that's developing. So that's why having twins is a rare phenomenon. You don't normally have two eggs that are being ovulated. It's just normally one. Because of that dominance phenomena. So external genitalia, we've already talked about this. We've talked about the homologs to the male system. The vagina is a muscular tube. It's got these rugi like we saw in the stomach. It's a stratified squamous epithelium. Hopefully you can appreciate that because That would be an environment where there would be physical abrasion. So obviously an individual wouldn't want to bleed every time they have intercourse and so there's a really thick, like 20 cell layer thick epithelium there for that reason. So here's the vagina there. You can see these rugi here There's the cervix. So that coagulated sperm Ideally, it sticks there. And then prostate specific antigen liquefies it And then the sperm can swim up into the uterus. So the uterus is a pear-shaped muscular organ. It's in the midline of the pelvis. And now you can see the uterus has three openings to it. Inferiorly cervix. And then up here at the fundus It's like we said, the fundic of the stomach. There's a fund of uterus as well. There's two openings to these tubes that are called fallopian tubes. Now, sometimes these fallopian tubes are called Oviducts. So that's fine. But I sort of like fallopian tube. They're also sometimes called uterine tubes. all these terms are fine. You'll see all these terms used. fallopians probably the coolest in my opinion. Here you can see that the ends of the fallopian tubes have these finger-like projections. These are called fimbria. Plural is fimbri. And they're muscular like structures and these fingers actually move like your fingers. And what they're trying to do is when the egg is released. You're trying to gather that egg into the fallopian tube so that it doesn't end up in the peritoneal cavity per se. So three regions, there's a body, there's a fundus and a cervix, there's the body right there. cervix down here, this is fundus right there of the uterus Three layers. There's a perimetrium. So that would be out here. A myometrium, that's the meat, the muscle of the uterus, which as you know is smooth muscle. And then there's an endometrium that has glands and vasculature. So here's how that looks. So these are uterine glands right here. And when we look at the endometrium, it's got two layers. It's got this layer that's called the functional layer, and it's got a basal layer. The basal layer has stem cells. The functional layer is the layer where implantation is going to occur. And if implantation doesn't occur, this is the layer that's going to slough off. So this is what's leaving with a menstrual flow is the functional layer of the uterine lining But again, it can be regenerated by the stem cells down here. Now, the uterine glands are secreting all kinds of things, but it depends on phase of the follicular cycle. And so they're secreting things like mucus, they're secreting things like prostaglandins and things like that. So there's various things secreted. We won't go into the details of that. in this class. So it really depends on what phase of the cycle that you're in. Okay, here's another nice look at these fallopian tubes. You can see right here is that ovarian ligament that we looked at The first image that we looked at of an ovary. There's many other ligaments that help keep it in place. There's a broad ligament right here. There is… a round ligament over here. So all of these things are important. But you can see the ovary right here and then the end of the fallopian tube here with these fimbrye. What's interesting about the fallopian tubes i find is that they're lined by a simple columnar epithelium that is ciliated. And the only reason I find it interesting is we really don't find that in the human body anywhere. It's really rare to find a simple epithelium that has cilia. Now we have pseudostratified ciliated columnar epithelium, but a straight up simple epithelium with cilia is relatively rare, but it makes a lot of sense to have it here because these cilia beat and what they do is they move the ovum along. And so that's important. And it can actually sweep along sperm as well. So largely what they're doing is they're moving the ovum And there's actually these non-ciliated cells that are called PEG cells. They secrete nutrients. to actually feed the sperm, but they also secrete inducers of capacitation Remember that when the sperm went through the epididymis, they became modal But then glycerophospholine was secreted and it basically turned them into zombies. Well, now they're not zombies anymore. So now they can actually swim And really, it's not that they can swim now because they can swim as soon as they were liquefied in the cervix. But now they're capable of fertilizing an ovum. They're active, they're operational, so to speak, they can fertilize an ovum. Now, you might say, you know, why would we want to incapacitate them to begin with? And this is the reason. We don't want them to be functionally active. We don't want them to burn any ATP more than they need for basal level of activity. Until they actually get where they have to go and do what they have to do. So they actually become capable of fertilizing an ovum only once. They're right there very close to where an egg will potentially be. So let's look at fertilization and implantation. So the secondary oocyte with its cumulus cells is going to be picked up by these fimbri. Here you can see that. So it's picked up here and then usually within one to two days, fertilization will occur. So we call that conception. And more often than not, it happens right here. So this is called the isthmus region. of the fallopian tube. This is called the ampulla region. That's where fertilization usually occurs in the amplio region about one to two days After ovulation. So remember the secondary oocyte is now going to complete meiosis II once it's fertilized. Now, in order to be fertilized, what has to happen is the sperm has to penetrate through the corona radiata And then it interacts with the zona pellucida proteins And then it undergoes its acrosomal reaction, which allows it actually to bind. and actually fuse with the membrane of the oocyte And now that oocyte is stimulated to complete meiosis II. And so now we can say. It's a mature egg. to mature ovum. The fertilized ovum is going to develop into a zygote, so it's a diploid organism. Obviously, sperm was haploid, 23 chromosomes. And the oocyte was as well with 23. So now this is a diploid organism. So make no mistake about it, a zygote is a single cell, but it's a living and breathing organism at that stage. Now, what it's going to do initially is undergo some hyperplasia. So it's going to go from a two cell stage to a four cell stage to an eight cell stage to a 16 cell stage. And all these cells are clones. They're identical clones. And they're pretty much identical clones up till you get to around like the 100, 200 cell stage. all clones. But somewhere around the 200 cell stage, you start developing what we talked about it earlier this semester. These cells start to differentiate and become what? Starts with a G. We develop our three germ layers, endoderm, ectoderm, mesoderm. So now there's differentiation Now we have cells that are different. And now they're not totipotent. And what we mean by totipotent is The first cell, the zygote, and up to the 200 cells that are clones from that. They can become any cell in the human body. They have this toady potential. But once you get to the 200 cell stage and you start differentiating the ectodermal, endodermal, mesodermal cells. those cells are just pluripotent. They can give rise to many different cells, but not all. Now, the embryo is implanted into the endometrial lining This is pregnancy that happens usually about five to seven days After fertilization. So this here shows the fertility window, so the probability of pregnancy from intercourse on days relative to ovulation. So here's the pregnancy rate here Here's cycle days here. And you can see that the peak window, peak fertility window is actually prior to ovulation So when you take a fertility tester here you can see that they show low fertility. That'd be somewhere around here. So after ovulation, it'd be a lower possibility of fertilization. And then high fertility would be somewhere around here or somewhere around here. And then obviously that is peak fertility there. Now, so what that means is basically one to two days prior to ovulation is the ideal time for copulation If you're trying to get pregnant. The reason for that is a Sperm live relatively long. five days or so. Whereas the oocyte or sorry, the embryo, that is Sorry, the oversight is only going to last like maybe 24 hours. So 12 to 24 hours is as long as the oocyte is going to lapis sperm is going to last a little bit longer. So the idea is you want the sperm actually staged there prior to the ovulatory event. And that increases the probability of fertilization. So I have a question for you here about these fertility testers. Hey, you want to hear a cool story? The guy doing my colonoscopy No, it's a cool story. The guy doing a colonoscopy is the father of one of my LAs. True story. I went to go see him. I went to go see him and he said hey um You seem like you know this stuff. And I said, yeah, I teach it. He goes, oh, yeah. He goes, my son has taken a class from a hard professor at MSU. I said, that's me. He goes, no, no, no. You said some hard professor. Because I was in… I think the troy area is where I saw him. So he's thinking I'm like teaching somewhere over there. And then it turns out that it's his son. I said, not only did your son have me, but he's one of my LAs. So it's kind of cool. All right. So that's what they're looking. Look, if you got LH, then you've ovulated, right? So… All right. The corpus luteum is a temporary endocrine gland. So it's formed from the emptied and collapsed graphene follicle. So once the graphene follicle releases the secondary oocyte, then it seals back up and becomes this temporary endocrine gland. and it's induced, this is very important for you to remember, it's induced by high levels of LH. So high levels of lh is not only what induced the formation of the corpus luteum. But keep it around. So it's composed of granulosa lutean cells and theca lutein cells. Let's see what these do. Basically, they do the same thing. So granulosa lutean cells They're derived from the mural granulosa cells. They produce progesterone. And they convert androgens to estrogens. So you're producing progesterone and estrogen. the colludean cells, same thing, producing progesterone and androgens. Now, what's the main thing? that it's producing. So the corpus luteum is producing a lot of progesterone and less estrogen. A follicle is producing a lot of estrogen and less progesterone. And we'll see that graphically in a little bit. Now, really important couple lines down here. Progesterone inhibits LH. which induces degeneration of the corpus luteum now think about that. high levels of LH is what stimulates the corpus luteum to exist. And look what the corpus luteum does. It produces progesterone, which inhibits LH. which causes the corpus luteum to die. So what does the corpus sodium doing? LH keeps the corpus luteum alive. Corpus luteum cranks out a lot of progesterone that inhibits LH. What's it doing? It's not negative feedback. It's basically on a pathway to kill itself, right? So it's on a pathway to kill itself unless something rescues it. So, and usually that happens in about seven days. So the corpus luteum is producing a hormone, progesterone, that is inhibiting a hormone, luteinizing hormone. that actually keeps it around. But only something can rescue it in the face of elevated progesterone. And that is fat, human chorionic gonadotropin. So if HCG is present. And the only reason it would be present is if there's a placenta in the body then hcg will keep the corpus luteum around even in the face of high progesterone. Now, that means there's a pregnancy. Which also means if there is no HCG, which means there's not a pregnancy. then the corpus luteum is going to do what? It's going to kill itself, right? The high progesterone is going to inhibit lh And it's going to degenerate into a corpus albicans. Again, kind of cool, right? The only thing that can rescue it is pregnancy and HCG. So this is an ovary right here, an actual image. Look how big a follicle can get Now, that's a remnant of a follicle, right? It's a graphene. follicle remnant because now it's a corpus luteum, but that's how big follicles can get as large as almost the entire ovary here. And these are symmetric follicles that have just died off. This thing is a temporary endocrine gland. It's cranking out high progesterone, low estrogen. Look at this one here. It's as big as the entire ovary. So this is what we call an ovary of pregnancy. So that ovary right there was taken from an organism. I don't know what organism That was during pregnancy. And that's how big that thing is And the main thing that it's doing is doing a lot of things, but the main thing it's doing is it's keeping the endometrium around. So it's preventing a menstrual flow, which is the last thing you want to happen if you have an organism implanted in your endometrium, correct? Okay. So let's look at this. We've already talked about all of it, but this is more of a schematic view of it. So we got some GNRH that's floating around. That's causing FSH and LH to be produced. No crazy levels or anything. But FSH comes over here and it stimulates theca and turno cells to produce Andrew Steinedione. The androstenedione goes through the granulosa cells and they convert it to estrogen. And so what happens is As we go this way, estrogen starts to increase. Not progesterone as much. But estrogen does. Now, remember that in order to get in androstenedione production, FSH stimulates theca interna cells to produce luteinizing hormone receptors. So you could draw an arrow here. luteinizing hormone has to stimulate those cells to produce androstenedione to begin with. So now estrogen increases. So estrogen is increasing in your plasma, progesterone, not as much. And if we go back to the previous slide. previous slides, estrogen inhibits FSH. So check this out. If estrogen inhibits FSH, then that means that follicle is being selected as the dominant follicle. Because it's inhibiting all the rest of follicular development. So by it cranking out a lot of estrogen, it's also reducing FSH and reducing further follicular development. Now, with the luteinizing hormone surge that estrogen is going to cause So not shown here. We'll get a luteinizing hormone surge. Well, actually, it's shown here. We stimulate ovulation. So we get ovulation that goes on. And then what happens is the remnant of the graphene follicle becomes a corpus luteum. Now that corpus luteum cranks out high progesterone, not so much estrogen. That feedback mechanism on the hypothalamus is different. What it does is it decreases LH and FSH. Now, if you decrease LH, that was what was keeping the corpus luteum around to begin with. So now the corpus luteum is on this time course of dying, which is in about seven days. it's going to become an atrophied corpus albicans. The only thing that can rescue it is that. So really it's these cells right here. They're called these syncytiotrophoblasts. You don't have to know that. just say placenta. The placenta is going to crank out hcg And that will keep the corpus luteum around. Which is really cool. So even though progesterone is really high and that's LH is really low, corpus luteum stays around so long as there's HCG produced. by a placenta, which means that there's actually a pregnancy. Now, with that said, let's talk about what the pregnancy test would be then. I was going to give extra credit if it was 80, so… But… Oh, very good. All right, so this is all tied together in these four different graphs. So one is the anterior pituitary hormones Two is the ovarian hormones. Three is the course of follicular development. And four is basically the course of the menstrual cycle, specifically looking at the uterine lining. And more specifically, the endometrium. So here's what happens. We got some GnRH that's being released. And then we get a little bit of FSH, a little bit of LH. And remember, the FSH is going to stimulate theca anterna cells to produce luteinizing hormone receptors, luteinizing hormone is going to bind to that, make androstenedione, give it to granulosa cells. They make estrogen. Look at that. estrogen starts going up. And you can see that that happens with the time course of follicular development. So primordial follicles to primary follicles. And now there's an antral follicle right there. Now, as estrogen is rising, you're also seeing that the endometrium is getting thicker and thicker. So estrogen rising with low progesterone, that's what's thickening the endometrium. And eventually we get to a point where estrogen surges so high and follicles are still developing. There's your graphene follicle now. that the surge in estrogen causes a surge in luteinizing hormone. Now, you know about luteinizing hormone causing the release of meiosis inducing substance and all that stuff. It's also going to stimulate this ovulatory event. And now we get ovulation. So we get ovulation and then potentially we get fertilization and potentially we get implantation into the endometrium. Now, if we don't, if we don't then what happens is this graphene follicle that becomes a corpus luteum Which, by the way, cranks out higher progesterone, lower estrogen. That corpus luteum will actually degrade into a corpus albicans If… something doesn't come by to rescue it. Because right now, look at lh low. LH is what was keeping the corpus luteum around to begin with. LH is now gone. So the corpus luteum is going to degenerate unless something comes in and rescues it, which would be HCG. So if HCG comes in from placenta because you have a pregnancy, corpus luteum sticks around cranking out high levels of progesterone lower levels of estrogen and that maintains that. Now, let's say that there wasn't a pregnancy Well, if there's not a pregnancy, then the corpus luteum becomes a corpus albicans and you get that. So you slough off the endometrial lining, you get a menstrual flow. So let's talk about what the pill is. Okay, very good. So let me make a point here. Most preparations of birth control are both estrogen and progesterone. Now, the reason this makes a lot of sense to you is this. Right here. Progesterone inhibits LH, so you can't ovulate. And estrogen inhibits FSH, so you can't develop follicles. Make sense? So that's why that's the most common preparation because it's really the most successful way of preventing a pregnancy. Now, there are also preparations that are just straight up progesterone. Which is technically enough. Because progesterone will inhibit the capacity to ovulate. And for some individuals that are sensitive to estrogen for some reasons, and what I mean by that is Maybe they have some conditions that preclude having increased estrogen levels in their body That's what they take. They just take straight progesterone. And normally it's a synthetic version of it. It's called progestin. So progestins are synthetic derivatives of progesterone All right, let's talk about what plan B is. Oh, no, wait a minute. We'll come to that in a second. Let's do this one first. So good. Whether it causes weight gain or not, I don't know. Maybe it does. But let me say this. I had a student in this class two semesters ago that was in my office And she said she felt like her heart was like beating out of her chest. So she came up to my desk and I took her pulse and it was like, I don't think 140 beats per minute. And I said, yeah, it's a little crazy, right? maybe one too many Celsiuses. And she actually said, yeah, she had one that day right But she said, I've been experiencing a lot of this lately. And I'm like, well, maybe you should get that looked at because it might be like SVT, supraventricular tachycardia, right? Because if you're just sitting there and your heart rate's 140, that's generally what would explain something like that. And so she goes, yeah, I'll take a look. I'll talk to my mom. She's an anesthesiologist. I said, put her on the phone right now. So she called her mom in the office and I was telling her mom, maybe you want to get her looked at. And her mom's like, well, what's her blood pressure? And I'm like, I don't know. There's not a doctor's office, right? But in a kind way, I said that, right? And so, but actually really smart of her mom. So she goes home later and she checks her blood pressure and it's like 70 over 50. So it's really low. And I mean, really dangerously low And it turns out the reason I use this now as an anecdote is this was her. So what the problem was is she was taking spironolactone for acne because of birth control. And what was happening was she had a lot of diuresis So she's losing a lot of fluid volume. And you know, if you lose blood volume, what happens to blood pressure? it goes down. What is the barrel reflex say? we got to get the heart going more. So we're going to send sympathetic nerve activity to the heart to contract harder but also to the SA node to crank up heart rate, right? So that's why our heart rate was flying. Our blood volume was really low. Okay, with that said, let's go to plan B. So anyone not know what Plan B is? Okay. Oh, my. My computer froze. Very good. Because progesterone inhibits what? What is progesterone inhibit? LH. So you don't what? You don't ovulate. Now, there's also something called RU486. This is an abortifacient. So this would be an abortion pill. Here, let's talk about what this does. Got to think long and hard about this one. It's really interesting physiology. or pharmacology, if you will. Someone explain to us how this works. Yep. Progesterone. All right, hold on one second. So progesterone receptor antagonist. Go ahead. that creates the environment for the space like the end. So if I'm antagonizing it. I'm like going to tear down my endometrial line. Yeah, perfectly said. So she says, hey. progesterone creates the environment for the baby. It keeps this endometrium really thick. So if I'm taking this, which is a progesterone receptor antagonist, then I can't maintain the endometrium. And then it gets sloughed off.