exploring spermatogenesis
Canto: So If Charles Darwin was alive today, he’d be gobsmacked at the facts derived from the ‘random variation’ end of his theory of natural selection from random variation. I’m talking about genes, DNA, genetic recombination and all that we know about meiosis and mitosis, spermatogenesis and oogenesis, genomics and epigenetics, mitochondrial DNA, ribosomes, mRNA, proteins and the like, none of which I’m particularly knowledgeable about – but surely even what I know about it all would make Darwin’s head explode.
Jacinta: Yes, and of course Darwin did all his studies on phenotypes, a term he would never have heard. He studied pigeons, finches, barnacles, fossils and a wide variety of plants. But he was never able to ‘crack the code’ of random variation. Why did offspring differ from parents? Why did those offspring vary from the utterly dysfunctional to the super-functional? For a time he considered pangenesis, his coinage, as a solution. This involved ‘gemmules’ inherited from both parents, blended together and somehow modified by the environment, presumably in a Lamarckian way. So Darwin never quite cracked the code of inheritance as we understand it today, but the work with plants which occupied his last years – allowing him to avoid the acrimony around human origins surrounding the publication of On the origin of species – produced important results for the understanding of plant reproductive biology. Take this quote from the Smithsonian magazine:
Darwin designed highly rigorous experiments and made predictions—which turned out to be correct—using his theory of natural selection. For example, he predicted that the myriad floral adaptations he saw existed to ensure that flowers were outcrossed, or fertilized by individuals other than themselves. He then tested this hypothesis with over a decade of pollination experiments and found that self-pollination leads to lower fitness and higher sterility. Inbred plants, like inbred animals, don’t fare well, at least over time—a phenomenon that’s now known as inbreeding depression.
Canto: Right, but let’s not get bogged down in the history of reproductive biology and the birth of genetics here, as it’s hard enough for me to comprehend meiosis and mitosis, gametes and zygotes and all the rest, as we understand it all today. We’ve previously written about meiosis, but I want to understand, or to begin to understand, in this post, how the process of producing gametes is so different in male and female mammals.
Jacinta: Okay, so we’re talking about gametogenesis. The male gametes are called sperm, the female gametes are called eggs, and so have two forms of gametogenesis, spermatogenesis and oogenesis. In this post I’ll focus on the male, saving the best for another post. So sperm is formed in the testes…
Canto: The ballsacks?
Jacinta: Uhh, well, the sack is just the sack, also known as the scrotum. Inside, you’ll find a testicle, hopefully. And as you well know there are, ideally, two of them. That is, two sacks, each with its testicle. And a testicle is about as complex as any other piece of biological machinery – a lifetime’s learning worth. Take this illustration, courtesy of ken hub.com:
Note the seminiferous tubules above. That’s where the sperm is formed, first by the mitotic division of a spermatogonial stem cell…
Canto: Eh what? How did they get in there?
Jacinta: Okay let me try to understand this for myself, but I may get more and more bogged down. It all begins at the beginning, during the early stages of male foetal development. The primordial germ cells differentiate in the testis, in these seminiferous tubules… But let me first fast forward to the end of the process and describe a complete, mature sperm cell or spermatozoon. That’s an active, motile sperm – plural spermatozoa, or just plain sperm. It’s divided into three parts, essentially, the head, the midpiece and the tail. At the head we find the acrosome and the tightly packed nucleus. The midpiece contains the mitochondria. which provides energy for the sperm’s motility, and the tail is essentially the flagellum, the sperm’s outboard motor, so to speak.
Canto: Okay, so that’s the end product – get back to the spermatogonial stem cells and the seminiferous tubules.
Jacinta: Fine. Spermatogonia are undifferentiated male germ cells, or sperm cells. It’s hard to find a simplified, but not overly simplified, explanation of how pluripotent or totipotent stem cells become germ cells, or any other cells for that matter, but it begins in the embryo. A cell signalling process in the embryo induces a small, transient proportion of the cell mass, the primitive streak, to become primordial germ cells (PGCs), along with other cells. This process is called gastrulation, in which the embryo begins to differentiate into distinct cell lineages. For the PGCs, according to a paper cited in Wikipedia, ‘The specification of primordial germ cells in mammals is mainly attributed to the downstream functions of two signaling pathways; the BMP signaling pathway and the canonical Wnt/β-catenin pathway’. This is essentially about regulatory proteins, I think.
Canto: This is getting too complicated for me. How come that second pathway is canonical?
Jacinta: See, you are paying attention. That Wnt/beta-catenin pathway gets a lot of attention in scientific papers, because we know that its deregulation is a problem in serious diseases and cancers. Basically these pathways are essential for embryonic development. The terms ‘canonical’ and ‘noncanonical’ are terms of art used to describe the standard production of Wnt proteins for development or homeostasis, and less well-known, or later-discovered pathways. I think. Anyway, let’s get back to spermatogonia, of which there are three types – A dark, A pale and B. The A dark spermatogonia are the reserves, and they don’t generally go through the mitosis process – they remain dormant. The A pale cells (so called because they have pale nuclei compared to the A dark cells) undergo mitosis to become the type B cells, which grow and develop to become primary spermatocytes, a process called spermatocytogenesis, truly. All of this occurs, as mentioned, in the seminiferous tubules of the testes, and begins at puberty.
Canto: Okay so how do these primary spermatocytes differ from spermatozoa, or how do they become spermatozoa?
Jacinta: The primary spermatocytes are diploid cells, so they need to undergo meiosis to become gametes. After meiosis 1, two haploid cells are formed, called secondary spermatocytes. And of course, being diploid cells undergoing that first process of meiosis, there’s this crossing over or recombination that occurs, shuffling the deck so to speak. And this is followed by meiosis 2, replicating the haploid cells, and so forth. But you ask how the spermatozoa are formed as an end product, so I need to take us back to those tubules in the testes. They’re packed with particular cells called Sertoli cells, and just outside the tubules are Leydig cells, which produce testosterone. Anyway, once these sperm cells have developed further they travel up to the epididymis via the rete testis, where they continue to mature, ready for ejaculation. They reach the rete testis, and presumably also the epididymis, by means of peristalsis, which you’ll know about from the intestines and other parts of the body.
Canto: Sort of. You think you know about stuff until you find out what you don’t know, which is overwhelmingly vast. Mais, continue..
Jacinta: So the last transformations, making them those mobile little tadpole-like critters, occur in the epididymis. But returning to those tubules. There are lots of Sertoli cells in there, and the sperm is developed in the gaps between them, strangely enough, but they acquire nutrients from those cells to help them along. Their journey between the cells takes them from the outer membrane of the tubule to the lumen. At the beginning of this journey they’re called spermatogonia. They’re going to go through this differentiating process to finally become spermatozoa. Now I’ve already partially described the first step, when a spermatogonium divides by mitosis, into two cells, one of which is kept in reserve, the Ad or ‘dark’ cell. The Ap or ‘pale’ cells continue on the pathway between the Sertoli cells towards the lumen, somehow becoming B cells – don’t know how that happens, but it involves mitosis, perhaps with nutrients from the Sertoli cells. I think, because the process of mitosis is continuous, those reserve cells are left behind all along the pathway. Or maybe not. But that pathway is obstructed along the way by ‘tight junctions’ between the Sertoli cells, which create separate compartments as they open and close before and behind the sperm cells (which are now called primary spermatocytes) like locks in a canal. Now these compartments, called basal and lumenal compartments, aren’t empty, they’re full of chemicals, signalling proteins and such, a different mix for each compartment, which add to the spermatocyte’s development. So the sperm grows as it travels along this pathway, accumulating more cytoplasm. And the junctions close very tightly after the sperm moves through, to prevent leakage into the next chemical environment. Now, somewhere along this pathway between the Sertoli cells, the primary spermatocyte is ready to divide into two secondary spermatocytes via meiosis, a very different form of cell division from mitosis.
Canto: Yes, meiosis has those two parts, ending with four haploid cells from one diploid cell, and genetic recombination to make us all unique.
Jacinta; Okay, moving right along, so to speak, those four haploid cells are now called spermatids, and they continue to mature in the lumen. They’re still not motile, they’re rounded cells at first, but they go through lots of changes, to the conformation of the DNA, for example, with histone proteins being replaced by protamines. We’re now entering the final processes, known as spermiogenesis, which I think occurs after transportation to the epididymis. The cytoplasm is removed, the acrosomal cap is formed, and the other structures I mentioned at the outset, the mitochondrial spiral and the fibres that form the flagellum, all take shape. This whole process, from spermatogonia to spermatozoa, takes about 65 days.
Canto: Okay, that’s enough of all that, I don’t particularly want to learn about seminal fluids and ejaculation at this point, fascinating though that might be – I’m more interested in the female stuff, the generation of eggs, known as oogenesis.
Jacinta: So that for you to detail in a future post.
References
https://embryo.asu.edu/pages/charles-darwins-theory-pangenesis
https://sciencing.com/difference-female-mammals-male-mammals-8092368.html
Spermatogenesis | Reproductive system physiology | NCLEX-RN | Khan Academy (video)
https://en.wikipedia.org/wiki/Germline_development#Germ_line_development_in_mammals
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