Transcription
So, the first lecture we are going to have on general embryology is gametogenesis. The lecture of gametogenesis is relatively long, and so I'm first splitting it into two. In this first part, we are going to look at the process of spermatogenesis, and in the second part, we look at the process of oogenesis. But we also need to understand some general principles about gametogenesis, and so I'll also address those ones in this part.
So, we define gametogenesis: the process of formation and development of the gametes. When you talk of gametes, we are the sperms, those are the male gametes, or the ova, the singular ovum, or the oocytes, and that is the name given to the female gamete. Remember, gametogenesis takes place within the gonads. Gonads, we are referring to the testes for the male gamete and the ovary for the female gamete. Don't use the term gonads to any other organ in the reproductive system apart from testes for male and ovary for female. The process of forming sperms is what we call spermatogenesis, and the process of forming the oocyte is what we call oogenesis.
The process of gametogenesis in general occurs in some four defined phases, and I want us to look at these four phases of gametogenesis. Take your mind back to a baby who has just been conceived and is now just developing in the mother's womb. This baby, you don't even know whether it's a baby boy or a baby girl. Take it back to even before the organs form. So that means that the testes has not formed if it's a male baby, or the ovary is not formed if it's a female baby. Take it back there. At that time, when we don't know whether this baby will become a baby boy or a baby girl, that is when things begin. That could be surprising, but that's when the stem cells that will give rise to the gametes in that baby begin to do something.
Now, what do they do? Those precursor cells for the gametes migrate towards and invade the indifferent gonads of the baby. You need to understand some terminology here, and the terminology you need to understand here is the term "indifferent gonad." So, what is this indifferent gonad? Understand it this way: when a baby is in the mother's womb, it's a time of development when we don't know whether this baby will be a girl or a boy. At least by the anatomical structures, you may know by genetic makeup, but you don't know by the anatomical structures that are there. One of the structures that will determine which direction the baby goes is the gonad that will be formed. So, there's a structure, there's an embryonic structure that is the primordium for the gonad. That embryonic structure is known as the indifferent gonad. The indifferent gonad is the primordium of the gonad, which means it is a structure that has the potential of either becoming the testis or the ovary. It is one baby, that structure is there, whether this baby will become a boy or a girl. It's a time of development when we don't know what they're gonna become. So, that's the time when we don't know what they're gonna become. That embryonic structure representing the gonad is called the indifferent gonad.
When that indifferent gonad is there, the stem cells, or rather the cells that will become the stem cells for the gametes, migrate from wherever they come from and invade the indifferent gonad. That is the first phase of gametogenesis. We will see where those cells come from shortly. We will see their names, but I want to get the concept. The first phase is the origin of the gamete stem cells. So, they originate from wherever they come from and they invade the indifferent gonad. When, before the baby is born, the number of cells that have migrated and invaded the indifferent gonad are about 100 cells. Let's just take that habitually. However, the intention we have is that the gonads should be in millions. At least we expect them to be many. So, what should happen to the gamete stem cells which have invaded the indifferent gonad? These cells need to undergo multiplication, and so that takes us to the second phase of gametogenesis, which is the multiplication phase.
During the multiplication phase, what happens? The multiplication phase is a period where the number of the gamete cells increase. There is a random increase in the number of the gamete cells, so that even though the stem cells we had were about 100, we now want them to be millions. Think through that again. Can answer this question: If I have only 100 cells and I want millions of cells, it makes sense for me to take these cells through cell division. And so the gamete cells will be taken through cell division so that we can have an increase in the number of cells. My question to you: Will this desire to increase the number of gametes involve mitotic cell division or meiotic cell division? Make a thought before I tell you what it is. So, I know you may have said meiosis, but that's not true. The gametes will be subjected to mitotic cell division. You may ask yourself, why mitosis? You know that gametes go through meiosis, so why are we talking about mitosis? It is true gametes undergo meiosis for a particular reason. It is also true their gametes undergo mitosis for a particular reason, and the reasons are very different.
If you want the gametes to increase in number, they are 100, you want them to be millions. If you subject those gametes to meiosis, you know what will happen? The maximum number of cells you get is just 400. Why do we say so? Because usually, once a cell has undergone meiosis, it enters what we call the G0 phase of the cell cycle, or let me put it in a simpler way: once a cell has undergone meiosis, it loses the capacity for cell division. So, if you start with 100 and you assume 100% success rate, the maximum that you can get from those gametes are 400 gametes. We don't want that. We want millions. So, what do you do? Gametes undergo mitotic cell division. Okay, gametes undergo mitotic cell division. The mitotic cell division that is undergone by gametes is a repeated one, which means even if you start with 100, you get 200. Those 200 can divide again, 400. The 400 can divide again, 800, and you can go on and go on. So, it involves multiple series of mitotic cell division. If you have multiple series of mitotic cell division, we are going to have exponential increase in the number of the gametes. I'm using the term exponential here intentionally. It's a mathematical term. Remember from earlier training, if you have 2 and you add 2 to it, it becomes 4. You add another 2, it becomes 6. Another 2, it becomes 8, 10, 12, 10, 16, 18, 20. Yes, we are increasing, but we are increasing with a constant number in this case, and that is called linear increase. Exponential increase is when you increase with an increasing factor. You start with 2, you go to 4, from 4 to 8, from 8 to 16, 32, 64, 128. You are increasing with an increasing factor, and that is what the gametes actually achieve. And so, exponential increase gives you a quicker increase than a linear increase.
Once the gonads have achieved the desired number of gametes in millions, now those individual cells can undergo the third phase of gametogenesis. The third phase of gametogenesis is involving establishment of the haploid state. So, basically, I call it establishment of haploidy. We establish the haploid state. The haploid state is established through meiotic cell division. The cells undergo meiosis. When cells undergo meiosis, they reduce their chromosomal number by half. Remember, human cells have 46 chromosomes, and that is what we call diploid or 2n. When those cells undergo meiosis, we have daughter cells which have 23 chromosomes, and that is what you call haploid or n. So, establishment of haploidy is the third step, or the third phase of gametogenesis.
Once the cells have established the haploid state, the last phase is the differentiation phase. The differentiation phase involves both morphological as well as functional changes which are characteristic of the gametes, and especially in the sperm, we are going to look at how that happens. Now, interestingly, even though gametes undergo these four phases in their development, how the two gametes undergo these four phases is a bit different. The first phase is universal. Whether sperms or oocytes will experience the first phase similarly. However, phase 2, phase 3, and phase 4 are very different for spermatogenesis and oogenesis, and it is because of that then that I want to now give you the objectives of this particular lecture. You know, that was the introduction. So, one of the objectives we are going to address in this lecture on spermatogenesis is to explain, basically, how phase one of gametogenesis takes place. The precursor cells for the gametes, where they come from, what do we call them? We look at that. But the second major objective is to look at how sperms undergo phase 2, mitotic division, phase 3, meiotic division, and phase 4, maturation process. That's our objective of this lecture.
Let's look at the first agenda: the origin of the gamete stem cells. Now, the precursor stem cells of the gametes differentiate from some embryonic cells that we call the primordial germ cells. So, that's the name given to the precursor cells that will give us the stem cells for the gametes. We call them primordial germ cells. These primordial germ cells are not within the indifferent gonad. They are not within the future testes. They are not within the future ovary. Where are they? They are outside the gonads. So, I'm saying they're extragonadal. But exactly where? They're in the walls of some embryonic structures that you may not be familiar with at this point in time, but you'll come to know them again. We call those embryonic structures the yolk sac. The yolk sac and the allantois. So, these primordial germ cells are present in the wall of the yolk sac and the wall of the allantois. These are the primordial germ cells present in the wall of the yolk sac and the wall of the allantois.
The primordial germ cells are pluripotent. I want you to understand the meaning of that. It means that they have the capacity of becoming multiple tissue lines. Yes, they are designated to become the gametes, but they can also become another thing. They can be bone tissue, they can become fat tissue, they can become epithelium. They are pluripotent, but right now they are being recruited to go for the sperms and the oocytes. I want you to have that in mind because it will become vital when we discuss the clinical importance of the process of gametogenesis. Okay. The primordial germ cells, wherever they've come from, whether the wall of the yolk sac or the wall of the allantois, they migrate towards and eventually they invade the developing embryonic gonad. I told you that that process happens before the developing embryonic gonad has committed to whether it will become the testis or the ovary, and that's what we call the indifferent stage of gonad development. So, these cells migrate into that embryonic structure. They don't know whether they'll be stem cells for sperms or stem cells for oocytes. They just migrate and invade.
And so, this image shows you the primordial germ cells, which are these ones, and that is the primordial gonad, or what I'm calling the indifferent gonad, that will either become the testis or the ovary. This cross-section also captures that. So, take this to be the indifferent gonad. The primordial germ cells come from the wall of the yolk sac in this case and invade the indifferent gonad. And of course, we have right and left. Those cells, those primordial germ cells that have invaded the indifferent gonad are the ones which are designated to become the stem cells of the gametes. The name given to the stem cells of the oocyte is oogonia. The name given to the stem cells of the sperm is spermatogonia. So, the primordial germ cells will become oogonia. They'll also become spermatogonia if the gonad becomes a testis. The decision on what gonad the indifferent gonad will become, we're not discussing now, but there are some factors that determine whether the indifferent gonad will be forming the testis or it will be forming the ovary. So, I'm saying we don't know what the indifferent gonad will become. The factors that will make it become the ovary or the testis, we're not discussing now. But if the indifferent gonad becomes the testis, primordial germ cells become spermatogonia, stem cells for the sperms. If the indifferent gonad becomes the ovary, the primordial germ cells become oogonia, stem cells for the oocyte.
Even though we are not discussing the mechanisms that help in gonad differentiation here, maybe there's a statement here I need to make: the presence of the primordial germ cells within the gonad is vital for its subsequent normal development, whether it is designated to become the testis or the ovary. It doesn't matter. If the primordial germ cells are not within the indifferent gonad, that gonad will not develop at all. Maybe that's fundamental. But if the primordial cells find themselves in the gonad, then fine. The gonad can either become the testis or become the ovary. But if not, I'll be asking you a question based on that, maybe next week. All right.
So, this is what we've said. There are four phases of gametogenesis. We have discussed the first phase of gametogenesis: the origin of the gamete stem cells. They come from the wall of the yolk sac and the wall of the allantois and invade the indifferent gonad before the baby is born, before the gonad even knows whether to become the testis or the ovary. That phase one is universal for both spermatogenesis and oogenesis. Phase two, phase three, and phase four are different when you're talking about oogenesis and when you're talking about spermatogenesis. So, I want us to see how then those three phases, that is, for our next objective.
First of all, we need to understand some things. The process of forming sperms occurs within the seminiferous tubules of the testes. So, these are the seminiferous tubules of the testes. These highly convoluted tubules are the seminiferous tubules of the testes. If you take a cross-section through one of them, it will look like this. I hope you can classify this epithelium. We can see that this is the attached side, that's the free side. So, it's epithelium, highly cellular. We can see several nuclear layers, so it is stratified, but we can't tell the specific shape of cells on the apical zone. So, you classify this epithelium as complex stratified epithelium. The complex stratified epithelium is also known as the seminiferous epithelium, as we see it in the testes. Very unique to the seminiferous tubules of the testes. It is this wall, it is within this wall that the sperms will be forming.
The process of spermatogenesis begins at the age of puberty. So, remember that. Yes, the primordial cells migrated and invaded. They remain dormant until the age of puberty. That is when things can begin to happen. So, from the age of puberty, what happens? The sperms begin to be formed. It takes about two months to form a single sperm. Like, I know that might sound a bit off, especially if you have some other things in mind. You will feel like it takes two seconds only, or at least less than a second, less than a minute. But it takes about two months to form a single sperm. Now, don't start thinking about those funny mathematical equations of high school that if it takes two months to form a single sperm, then how long will it take to form millions of sperms? So, you multiply two months by millions and millions of sperms, then you realize, hey, you're unlikely to live those million months. It's like saying it takes you four years to train in the course you're doing. So, if it takes you four years, or five years, or six years, wherever, to do the course you're doing, then how long does it take to train 40 of you, 100 of you? You want to multiply 4 by 40, or 4 by 100, then say it takes those many years. It will still be the same number of years that one person takes, four years, except that it's done in bulk and continuously. So, when you finish first year, you go to second year. There's another first year coming in. One day, it'll be fourth year, and then by that time, there will be three generations behind you, and it continues like that. The sperms take a similar model.
The process of spermatogenesis ends when the man is dead. Only death separates men from spermatogenesis. Someone said, and I'm quoted, anyway, spermatogenesis continues throughout life. That's the point I'm passing across. The rate at which sperms will be formed in an older person may, however, be low compared to the rate at which sperms would be formed in a younger person, but either way, the sperms will still be formed. So, maybe at the age of 90, 100, the rate of spermatogenesis, the sperm count might be low, but they're still there.
The most optimal temperature for spermatogenesis is a temperature that's about two to three degrees below the normal body temperature. So, if your normal body temperature is 36, 37, then let's go with about 34 degrees. That's the most optimal temperature for spermatogenesis, and it explains why the testes then hang outside. I actually find that term a bit off, but maybe it's the best time to use that. The testes must hang outside so that it can cool. The sort of the scrotum hangs outside so they can cool the testes. This is a cooling effect. Men need to know that they need to keep that thing cool.
The cells that support the developing sperms are known as Sertoli cells. These Sertoli cells provide structural support to the sperms. They also help in providing nutrition to the sperms. They help in removing excess cytoplasm from the sperms, and they protect the sperms from being subjected to all components of blood. They protect the sperm, so they form what we call the blood-testis barrier, among other things that they do. So, this slide just captures some general aspects about spermatogenesis, but let's now go step by step on what happens with the sperms.
This, we've already said that during phase one of gametogenesis, we have what we call primordial germ cells. They arise from the wall of the yolk sac and the wall of the allantois. Those are extragonadal structures, and what they do, they migrate and invade the indifferent gonad. If the indifferent gonad becomes a testis, then these primordial germ cells will become the stem cells of forming sperms, which we call spermatogonia. So, spermatogonia here are the sperm stem cells. This process takes place before birth, and that is phase one of gametogenesis. So, the cells have migrated from the wall of the yolk sac and have invaded the developing indifferent gonad. If they're going to become the testis, then these ones will become spermatogonia. Spermatogonia remain dormant in the testes until the age of puberty, and that is when they can start multiplying to form the sperms, and that is why we say that spermatogenesis begins at the age of puberty.
So, what happens to spermatogonia? From the age of puberty, spermatogonia must undergo phase two of gametogenesis. Remember, it was the multiplication phase. It involves several series of mitotic cell division, leading to the formation of a group of cells we call the primary spermatocytes. Because it is multiple series of mitotic cell division, we have an exponential numerical increase in the number of cells from possibly 100 or a thousand, whatever number you give it, you have millions and millions of cells. The primary spermatocytes are therefore present in millions, inasmuch as the spermatogonia were few. This process of mitotic cell division, or let me say repeated mitotic cell division, that leads to the formation of primary spermatocytes, that process is otherwise known as spermatocytogenesis. That is phase two of gametogenesis.
The primary spermatocytes then undergo phase three of gametogenesis. Phase three of gametogenesis involves establishment of the haploid state. Haploidy is a state where the cell has only one set of the chromosomes, in this case, 23 chromosomes, instead of 46, which we call the diploid state. Now, the primary spermatocytes are diploid cells. They are 46 chromosomes. The primary spermatocytes must undergo meiosis so that we now reduce the chromosomal number by half. So, it will undergo meiosis. Remember, meiosis takes place in two stages or in two phases: meiosis one and meiosis two. Meiosis one involves, sorry, meiosis one involves separation of homologous chromosomes. So, those 23 pairs of chromosomes, the pairs are separated so that each cell, each chromosome will go separately. They'll no longer be paired. So, eventually, the daughter cells will have 23 chromosomes each, and those are the ones we call the secondary spermatocytes. Secondary spermatocytes undergo the second meiotic division. The second meiotic division involves separation of chromatids. Remember, each chromosome has two chromatids, and one chromatid is a copy of the other one. So, meiosis two involves separation of chromatids, and the daughter cells we get there are called spermatids. So, spermatids are haploid cells. We get four spermatids from one primary spermatocyte. Remember, spermatids will now be haploid, as opposed to primary spermatocytes which were diploid. That is phase three of gametogenesis.
Now, let's look at phase four of gametogenesis as with regard to spermatogenesis. We mentioned that phase four of gametogenesis involved morphological and functional maturation processes. Let's see how sperms undergo morphological and functional maturation processes. Spermatids look like this: rounded cells. We know that's not the kind of cell we have in mind when you talk about sperms. This is what you have in mind, but that's what we have right now. So, the spermatids must undergo morphological changes. The morphological changes that are undergone by the spermatid is collectively termed spermiogenesis. This is a series of morphological changes that the spermatid undergoes, and the resultant cells that we get from that process is this one, which you call spermatozoa. It's a series of morphological changes that are undergone by the spermatid to give us the spermatozoa. We call that process spermiogenesis.
What will spermiogenesis particularly entail? Let's look at this image to help us capture a few things that spermiogenesis entails. One of them is the shedding of excess cytoplasm. So, excess cytoplasm is shed off, and Sertoli cells help here to engulf that extra cytoplasm. Apart from shedding off of excess cytoplasm, the other thing that happens to the sperms is the rearrangement of the mitochondria to the neck piece, or rather to the midpiece. Rearrangement of the mitochondria to the midpiece of the sperm. The other thing that happens is formation of the acrosome. The acrosome is this thing here that contains enzymes, and we'll see its role when we look at fertilization. Formation of the acrosome occurs during spermiogenesis, and the acrosome is actually formed from the Golgi apparatus. You might be tempted to think that the acrosome forms from the nucleus, but that's not true. It forms from the Golgi apparatus. All right. So, I've told you three major things that take place during spermiogenesis: shedding off of the excess cytoplasm, rearrangement of the mitochondria to the midpiece, and formation of the acrosome. Because spermiogenesis involves a lot of changes in the cell, we sometimes call this stage cytodifferentiation.
Now, the spermatozoa that is formed from spermiogenesis is the mature sperm cell. Spermatozoa is the mature sperm cell. Although it's a mature sperm cell, it may not yet be ready for fertilization. And you ask yourself, why? And the answer is, maybe it has not fully undergone the maturation process, especially the functional maturation process. So, morphologically, the cell is mature, but functionally, the cell may not be fully mature, and so it may not be ready for fertilization at this point. So, what must happen to it? First, the spermatozoa, when they're formed, they're still attached to the wall of the seminiferous tubules, like this. For now, you see the way they're attached there, or maybe let me use this one where they are attached there. They can't really fertilize there if they're attached. First, they must be freed. The process of freeing the sperms from the wall of the seminiferous tubules into the lumen of the seminiferous tubules is not called ejaculation, but it is called spermiation. Now, you know in ejaculation, the sperms are released from inside to wherever they go outside. That is ejaculation. Spermiation is the release of sperms from the wall of the seminiferous tubules into the lumen of the seminiferous tubules. It's like the way when you release the oocyte, we call that ovulation. So, when you release the sperm, we call it spermiation.
Once the sperms have been released free into the lumen of the seminiferous tubules, they can now move. Now, many sperms are released into the lumen of the seminiferous tubules per day, in the order of millions. When you read that, when you see that, you then realize that spermatogenesis must be very wasteful. It doesn't make a lot of economic sense. Let's go on. So, about 300 million sperms are released into the lumen of the seminiferous tubules per day, which means that even right now, if you're a man, it's actually happening. Once the sperms have been released into the lumen of the seminiferous tubules, what happens? So, see here, this is the seminiferous tubule where spermatogenesis takes place. By the way, those spermatogonia would be on this other side of the wall of the seminiferous tubule, and for those two months of development, the sperms move that way. And so, the ones you see here are actually the ones which are about to be permeated into the lumen. These ones are actually spermatozoa. So, it takes about two months to move from here up to there, during which the functional changes, anatomical and functional changes take place.
Once the sperms are within the lumen of the seminiferous tubules, they are free there. They can now move from the lumen of the seminiferous tubules and move to the epididymis. Now, how they move, look in this image. These are the seminiferous tubules of the testes. From there, they move to this part, which we call the straight tubules. So, these are the straight tubules. Multiple straight tubules meet within this complex structure, which we call the rete testis. The rete testis is an anastomosis of the straight tubules of the testes. So, from the seminiferous tubules, sperms go to the straight tubules, then within the rete testis, which is an anastomosis. From the rete testis, sperms go to these things called efferent ductules. These efferent ductules constitute the head of the epididymis. They constitute the head of the epididymis, which means that actually they're already within the epididymis. Now, histologically, we talk of the epididymis as having the efferent ductules and this long thing here, which we call the duct of the epididymis. But from a gross anatomy perspective, we talk of the epididymis having a head, a body, and the tail of the epididymis. I like looking at it in this case from a histological perspective. So, the efferent ductules, then the duct of the epididymis, then to the vas deferens, or otherwise known as ductus deferens. Those are the sites of storage.
Sperms during storage of sperms, another thing will happen. We call it decapacitation. During storage of sperms, sperms undergo what we call decapacitation. What is decapacitation? Decapacitation is the application of what we call the capacitation factors around the head of the sperm. So, in this image, you see some blue, sorry, that should be green, green thing applied on the head of the sperm, somewhat to just blindfold or to protect or to cover, whatever you want to call it. It's a glycoprotein material applied on the head of the sperm. Decapacitation is important. Why? If sperms are not decapacitated, in simple terms, they'll start looking for the oocyte. Now, you see, even if they look for the oocyte here, they will never find it. Remember, the sperms are still within the epididymis and the vas deferens. Definitely, the oocyte is not there. So, if they start looking for the oocyte there, they'll not find it. They'll be very tired. So, that when now they are put in the actual battlefield in the female tract, they may just look at one another and do nothing much. They're so tired. So, maybe that's why the sperms must undergo decapacitation. So, this decapacitation makes them a bit inactive. The sperms will be inactive. That does not mean that they can't really be motile. They are still motile, except that the motility is not maximal, and of course, the identity molecules of the sperms have also been masked by the decapacitation factors. So, sperms undergo decapacitation during their storage. Decapacitation occurs in the epididymis as well as the vas deferens.
One day, they will be ejaculated. So, the sperm that a man ejaculates is a sperm that has been decapacitated, well, if they are ejaculated, hopefully in the right place. So, the sperms will be in the female reproductive tract. Before we proceed from there, how long do you think sperms can remain viable within the male reproductive system? We are saying that millions are being produced per day, but we know that men do not necessarily ejaculate per day. Well, I'm making an assumption, a safer one. So, it means that sperms will be stored, but how long can a man store the sperms and the sperms will still be viable? It's usually about two to three months. So, the sperms that a man produced some two months ago are still viable. That's what that means. They can remain viable for about two to three months.
Once the sperms are within the female reproductive tract, which means they have found themselves there in one way or another, what happens to them? The number of sperms which are deposited in the female tract are so many. We'll talk about it again when we discuss fertilization, but about 300 to 500 million sperms are deposited in the vagina in a single ejaculate, taking an assumption that that ejaculate was a normal volume ejaculate of about two to six, and let's go with them maybe four to five ml. So, the sperm count there will be about 300 to 500 million sperms. Although that high number, usually only one percent or about one percent will climb up the cervix. The other 99 percent remain there in the vagina and will just drain off. Unfortunately, I can hear somebody saying, "Ouch." Anyway, the one percent that climb up, the lucky ones, will then climb towards the endometrial cavity and swim towards the fallopian tubes, either direction. During that journey, those sperms will undergo the last maturation step, and the last maturation step is known as capacitation.
Now, what is capacitation? Capacitation is basically the removal of the glycoprotein material. The removal of the glycoprotein material from the head of the sperm. Remember, we talked of sperms which were formed and then went to the epididymis, then the decapacitation factors applied. So, this is the sperm that would be ejaculated. When it reaches the female tract, the decapacitation factors are now removed. So, capacitation is the removal of the decapacitation factors from the head of the sperm. This achieves two things: it makes the sperms be more motile, which means they can now swim faster, and two, it has unveiled the identity molecules of the sperms, which means the sperm can now see where the oocyte is. Capacitated sperms are therefore ready for fertilization.
All right, let's finish with the parts of a mature sperm. So, this part here is what you call the head of the sperm. It contains this one, the nucleus, as well as that one, the acrosome. This is the neck of the sperm. This region is the midpiece of the sperm, which contains a row of mitochondria. This detail of the sperm, which has the tail, that is the process of spermatogenesis. So, our next topic will be on oogenesis.