Overview – The Male Reproductive System
Plate 17-1. The Seminiferous Tubule Of The Testis
Plate 17-2. The Epididymis
Plate 17-3. The Vas Deferens
Plate 17-4. The Prostate Gland
Plate 17-5. The Seminal Vesicles
The micrographs in the preceding chapters have illustrated the diversity of cellular microarchitecture that makes up the various systems of the human body. That such a complex and stunningly beautiful microarchitecture exists is remarkable. What is even more remarkable is the fact that all the 50 trillion cells that make up the human body come from one cell – the fertilized egg. The present chapter deals with the male reproductive system, the system that produces the sperm that fertilizes the egg. Perhaps the simplest way to describe the male reproductive system is to start with the end product, the mature Spermatozoon. The male Spermatozoon has been aptly, if somewhat ironically, described as “. . . a nuclear war-head of paternal genes powered by an active tail.” (Passmore, H., and Robson, J.S.: A Companion to Medical Studies. Vol. 1. London, Blackwell Scientific Publications, 1974. 198)
As shown in the drawing in Figure 17-1, a human Spermatozoon is a thin cell, some 50 Â µm long, that has a compact Nucleus at one end and a tail at the other. The Nucleus, being Haploid, contains one half the normal number of chromosomes; the diploid number will, of course, be restored at fertilization, when sperm and egg combine to pool their genetic material. The genetic material within the Spermatozoon is highly supercoiled, compact, and compressed. This nuclear condensation not only streamlines the sperm, but protects the genes during their long and hazardous journey to the egg. Of the 100 million spermatozoa that enter the female reproductive tract at a given time, only one reaches, penetrates, and fertilizes the egg Behind the discus-shaped Nucleus lies the tail, which is divided into three parts: the midpiece, the principal piece, and the endpiece. The core of the sperm tail is the Axoneme – a motile “9 + 2” complex of microtubules and associated proteins, identical to theAxoneme of motile cilia, that is capable of propagating waves along its length in response to the hydrolysis of ATP. The thick midpiece of the sperm carries a “battery pack” of Mitochondria tightly spiraled around the Axoneme to produce the ATP required for the motility of its flagellar tail. The Seminal Fluid in which the sperm are suspended is rich in Fructose, which is thought to serve as a substrate for ATP production by the midpiece Mitochondria. The entire male reproductive system is established for the production of prodigious numbers of spermatozoa and the Seminal Fluid in which they are suspended upon ejaculation.
The general layout of the male reproductive system is illustrated in Figure 17-2. The testicles, or testes, are both endocrine and exocrine organs. The endocrine portion consists of Interstitial Cells (also called Leydig cells) that produce testosterone. The exocrine portion consists of siminiferous tubules that produce spermatozoa. As shown in Figure 17-2, each testes is subdivided into 250 lobules. Each Lobule contains from two to four seminiferous tubules. Each Seminiferous Tubule is a single tube, some 70 cm long, that is lined by a Germinal Epitheliumthat produces spermatozoa. Given these figures, both testes, taken together, contain 1,500 seminiferous tubules whose total length spans 1050 m or 1.05 km. This is an enormous amount of Germinal Epithelium, and it produces a correspondingly enormous number of spermatozoa. The 100 million spermatozoa in a single ejaculate, isolated and aligned head to tail in a chain, would extend for 5 km. The double-helical DNA molecules from the Nucleus of a single spermatozoan, isolated and stretched out, would make a line about 0.5 m long. Were one to perform that operation on all of the 100 million sperm nuclei in one ejaculate, the DNA molecules within the sperm nuclei from one ejaculate alone would stretch for 50,000 km — which would, at the equator, span the globe 1.2 times.
Clearly the male reporductive system makes a lot of spermatozoa. It has to, for not only are the odds quite small of a single Spermatozoon reaching the egg, but the odds of the egg being fit for fertilization at the time of sperm arrival also are quite small. Consequently, the male reproductive system knows little rest, and is constantly engaged in the production, maintenance, nutrition, and, in times of sexual inactivity, resorption of large quantities of spermatozoa.
The “production line” in the Germinal Epithelium, a process know as Spermatogenesis, starts with stem cells called Spermatogonia. Under appropriate conditions of hormonal stimulation, Spermatogonia divide mitotically and give rise to Primary Spermatocytes. These spermatocytes undergo meitoic division, giving rise to Secondary Spermatocytes. Secondary spermatocytes undergo a second meiotic division and produce spermatids. Spermatids do not divide; instead, they undergo Spermiogenesis, a marked and complicated morphogenetic transformation into spermatozoa.
When fully formed spermatozoa are shed from the Germinal Epithelium into the lumen, they travel along the Seminiferous Tubule and enter the Epididymisthrough a series of intermediate ducts. The Epididymis, a 1-cm coiled tube (which if unraveled, would measure 6 m), is closely applied to the outer wall of the Testis. As spermatozoa travel through the Epididymis, they undergo the process of Capacitation; that is, they acquire the capacity to move and fertilize the egg. In addition to participating in sperm Capacitation, the Epididymis resorbs much of the testicular fluid secreted by the seminiferous tubules. Sperm are stored in the large tail, or cauda, of the Epididymis and are passed into the vas deferens during ejaculation. Sperm are propelled along the length of the Vas Deferens into the ejaculatory ducts that lead into the Urethra, where they are mixed with Seminal Fluid produced by the Prostate Gland and the seminal vesicles. The combination of sperm and seminal fluid is known as Semen; Semen is the substance that enters the female reproductive tract during copulation.
This chapter examines the structure and function of the seminiferous tubules, the Epididymis, the Vas Deferens, the Prostate Gland, and the seminal vesicles. The microanatomy of the female reproductive system will be described in the next chapter.
The Testis is both an exocrine and an endocrine organ. The exocrine portion consists of a series of highly coiled seminiferous tubules that make sperm; the endocrine portion consists of specialized cells called interstitial cells (also called Leydig cells) that secrete testosterone. The Interstitial Cells lie in the connective tissue between adjacent coils of seminiferous tubules.
Each Testis is divided into 250 compartments called lobules. Each Lobule, in turn, contains from one to four serniniferous tubules. As described in the overview, each Seminiferous Tubule is quite long; a single one may measure up to 70 cm. Because each long tubule is packed into the confines of a single Lobule, the Seminiferous Tubule is folded back on itself in a highly complex manner. Consequently, a section through the Testis reveals the seminiferous tubules as a series of circular profiles.
Figure A is a light micrograph of a cross section through a serniniferous tubule within one of the lobules of the Testis. The cells of the spermatogenic lineage are stacked in 4 to 8 layers; although the cells vary in appearance, most are cuboidal, with the exception of the long, thin spermatozoa. The two major classes of cells within the serniniferous tubule are supporting cells and Spermatogenic Cells. The supporting cells consist of one type of cell called the Sertoli Cell. The spermatogenic cells consist of five morphologically distinct classes of cells: Spermatogonia, Primary Spermatocytes, secondary spermatocytes, spermatids, and spermatozoa. At first glance, these cells can be quite difficult to tell apart. Close study of their nuclei, however, reveals distinct differences in nuclear structure – the key to their identification.
In Figure A, the Sertoli cells (S) can be recognized by their large, round, pale nuclei and prominent, centrally located nucleoli. The Sertoli Cell nuclei are usually located next to the Basement Membrane at the periphery of the Seminiferous Tubule. Sertoli cells span the entire thickness of the epithelium from the basement membrane to the lumen of the tubule. All of the cells of the spermatogenic series are intimately associated with the Sertoli cells and seem to be nourished by them. The Spermatogonia (G), whose nuclei are also located at the periphery of the tubule, undergo mitotic division and give rise to the Primary Spermatocytes (P). Primary spermatocytes spend much of their time in meiotic prophase and are readily identified as cells with large nuclei that contain condensed Chromatin.
Primary spermatocytes divide meiotically to form Secondary Spermatocytes, which resemble primary spermatocytes but are much smaller. Secondary spermatocytes undergo Meiosis very rapidly and give rise to spermatids (ST). Since Secondary Spermatocytes cycle through their stage so quickly, they are rarely seen; none are present in these micrographs. Spermatids, however, have a long life, are abundant, and are readily identified as small cells, often near the lumen, with small, pale nuclei. Spermatids undergo no further division; instead, they undergo Spermiogenesis, in which they are morphogenetically transformed into spermatozoa (arrow).
Many of these cells are readily apparent in Figure B, an electron micrograph of a cross section through a portion of a serniniferous tubule. Compare the appearances of Spermatogonia (G), Sertoli cells (S), primary spermatocytes (P), and spermatids (ST) in this electron micrograph with those of the same cells in Figure A. Careful examination of Figure B will reveal some of the key features of Spermiogenesis. In some of the spermatids, for example, the forming Acrosome (*) – a large Lysosomeon the head of the sperm that helps it to penetrate the egg – can be seen as a large vesicle, derived from the Golgi Complex, that is closely applied to the Spermatid‘s Nucleus. In addition, the Mitochondria that will wrap themselves around the midpiece can be seen taking station in the Cytoplasm of the Spermatid.
Plate 17-1, Figure A. Light micrograph of a cross section throu gh the Testis of the cat. Figure B. Electron micrograph through part of a Seminiferous Tubulefrom the same Testis. C, capillary; CT (Figure A), connective tissue; G, spermatogonium; I, interstitial cell (Leydig Cell); P, primary Spermatocyte; S, Sertoli Cell; ST, spermatids; arrow, developing spermatozoa; * (Figure B), developing Acrosome. Figure A, 400 X; Figure B, 1,900 X
When Spermatogenesis is complete, fully formed spermatozoa leave the serniniferous tubules, pass through a series of short ducts, and enter the Epididymis. The Epididymis is one long, thin tube that is tightly coiled and closely applied to the posterior surface of the Testis. When seen with the naked eye, the Epididymis is a whitish structure, some 7 cm long, that consists of a head (the caput), body (the corpus), and tail (the cauda). Stretched out, the Epididymiswould be a single tube that measures over 6 m long. Consequently, spermatozoa entering the Epididymis at the head and exiting into the Vas Deferens at the tail take a long journey. During that journey, sperm become both motile and fertile. Although it is widely believed that the Epididymis participates in sperm’s maturation and contributes to the development of their motility and fertility, the precise mechanisms by which these functions are accomplished are still unknown. Large numbers of spermatozoa are stored in the lumen of the Epididymis prior to ejaculation, and it is believed that the Epididymis actively resorbs fragments of Cytoplasm eliminated during Spermatogenesis and resorbs entire spermatozoa in times of sexual inactivity.
When viewed with the light microscope at low magnification, a section through the Epididymis presents a large number of circular profiles that represent cut portions of the supercoiled tube, or duct, of the Epididymis. Figure A, a light micrograph taken at intermediate magnification, shows a cross section through one of these coils. Here, the lumen (L) of the Epididymis contains many spermatozoa. The Epididymis is lined by a pseudostratified Columnar Epithelium (E) that contains two types of cells: principal cells and basal cells. The principal cells (P) are tall, columnar cells topped by many long, thin Microvilli (arrow) called stereocilia. The Basal Cells are small, round cells that lie next to the Basement Membrane. The Basal Cells undergo mitotic division and serve as stem cells; the progeny of Basal Cells grow, differentiate, and replace worn-out principal cells. The epithelium is surrounded by several layers of circularly arranged Smooth Muscle fibers (SM). These Smooth Muscle fibers contract rhythmically and slowly propel the spermatozoa along the length of the Epididymis from its head toward its tail. The smooth muscle fibers are surrounded by loose connective tissue (CT) that serves to bind together the coils of the Epididymis.
Figure B is an electron micrograph of a thin section through the same Epididymisshown in Figure A. Here, the lumen (L) containing the spermatozoa is at the top of the field; the Smooth Muscle (SM) surrounding the epithelium is at the bottom. The pseudostratified Columnar Epithelium rests atop the Basement Membrane(BM). Both cell types of the epithelium are evident in this low-magnification electron micrograph. The small, round Basal Cells (B) may be seen next to the basement membrane. The remainder of the cells are the principal cells (P) – slender, columnar cells topped by hundreds of long, thin Microvilli (arrow). The nuclei (N) of the principal cells, located at the basal pole of the cell, are long and thin and display an unusual folded appearance. Just above the Nucleus of each Principal Cell lies a very well developed Golgi Apparatus (G). Large numbers of electron-dense vesicles (Ly) lie above and below the Golgi. These vesicles are believed to be lysosomes – organelles directly involved in the intracellular digestion of material taken up from the lumen of the Epididymis by Pinocytosis.
Plate 17-2, Figure A. Light micrograph of a cross section through the duct of the Epididymis of the squirrel monkey. B, basal cell; CT, connective tissue; E, epithelium; L, lumen filled with spermatozoa; P, Principal Cell; SM, Smooth Muscle; arrow, stereocilia. 800 X
Figure B. Electron micrograph of the same Epididymis shown in Figure A. B, basal cell; BM, Basement Membrane; G, Golgi apparatus; L, lumen; Ly, Lysosome; N, Nucleus of Principal Cell; P, Principal Cell; SM, Smooth Muscle; arrow, long Microvilli (stereocilia). 1,500 X
The Vas Deferens, also called the Ductus deferens, is a thick, highly muscular tube, 45 cm long and 2.5 mm wide, that connects the Testis with the Urethra. It begins at the tail of the Epididymis, passes into the spermatic cord, and ultimately joins the Urethra in the vicinity of the bladder and the Prostate Gland. The diagram in Figure 17-1 clarifies the position of the Vas Deferens in the male reproductive system.
The purpose of the Vas Deferens is to propel live spermatozoa, some 100 million per ejaculate, from their site of storage in the Epididymis to the Urethra. At the moment of ejaculation, sperm delivered by the vas to the Urethra are mixed with Seminal Fluid delivered by the prostate and seminal vesicles to form Semen. To reach the Urethra from the Testis, sperm must travel some 45 cm. Consequently, the Vas Deferens must move sperm along its length rather rapidly. To accomplish this task, the 1-mm-thick wall of the Vas Deferens is richly endowed with Smooth Muscle fibers and elastic fibers. During the process of ejaculation, the smooth muscles, stimulated by the Autonomic Nervous System, contract in a wavelike manner, rapidly squeezing the sperm up the length of the tube through its narrow lumen.
Figures A and B are a pair of light and electron micrographs of cross sections taken through the vas deferens of the squirrel monkey. Here, the small, star-shaped lumen (L) is lined by a pseudostratified Columnar Epithelium (E). As in the Epididymis, the epithelium contains small, round Basal Cells (B) and tall columnar cells. The columnar cells are topped by long, slender Microvilli, called stereocilia (S). (The term “stereocilia” is misleading, for stereocilia are not cilia at all, but elongated Microvilli.) Just beneath the epithelium lies a Lamina Propria (LP) rich in elastic fibers. The Lamina Propria binds the epithelium to the underlying layer of Smooth Muscle (SM). Classically, the smooth muscle is believed to be arranged in three layers: an inner longitudinal layer, a powerful middle circular layer, and an outer longitudinal layer. In the micrographs at right, this arrangement is not apparent; most of the Smooth Muscle fibers here are caught in oblique section, indicating that many of them are wound in a spiral fashion around the lumen in the core of the Vas Deferens.
Plate 17-3, Figures A and B. Light and electron micrographs of cross sections through the Vas Deferens of the squirrel monkey. B, basal cell; E, pseudostratified Columnar Epithelium; L, lumen; LP, Lamina Propria; S, stereocilia (long Microvilli); SM, Smooth Muscle. Figure A, 500 X; Figure B, 900 X
When mating occurs, live spermatozoa that are ejaculated from the male reproductive tract are suspended in Seminal Fluid. The average volume of a single ejaculate, which contains on the order of 100 million spermatozoa, is about 3.5 ml. The ejaculated material, Semen, contains 10% spermatozoa and 90% Seminal Fluid. The Seminal Fluid consists of the combined secretions of the seminiferous tubules, Epididymis, Prostate Gland, seminal vesicles, and small glands called the bulbourethral glands.
The bulk of the Seminal Fluid is elaborated by the Prostate Gland, a chestnut-shaped organ some 3 cm in diameter that surrounds the base of the Urethra and the neck of the urinary bladder. The Prostate Gland is a collection of 30 to 50 branched tubuloacinar glands, embedded within a dense fibromuscular stroma, that empty their secretions into the Urethra. These tubuloacinar glands secrete Prostatic Fluid and store it until the moment of ejaculation. Prostatic Fluid is a viscous material that has many ingredients, including acid phosphatase, citric acid, and Prostaglandins. Prostaglandins, which are a class of long-chain hydroxy fatty acids, have many functions, including the stimulation of rhythmic contractions of uterine smooth muscle. Consequently, the Seminal Fluid, which contains Prostaglandins, not only provides a fluid medium in which sperm can swim and live for long periods of time, but it also promotes muscular contractions of the female reproductive tract that accelerate the delivery of spermatozoa to the waiting egg.
Figures A and B are a matched pair of light and electron micrographs of serial thick and thin sections taken through the Prostate Gland of the squirrel monkey. Figure A, taken at relatively low magnification, provides a survey view of several of the tubuloacinar glands (G) and the fibromuscular stroma (S) that surrounds them. In the center of the field, two acini of one of the glands contain dense inclusions called Prostatic Concretions (C). Commonly found in middle-aged and older males, Prostatic Concretions are thought to represent portions of the secretory substance that with time have become crystallized or mineralized.
The cells of the secretory acini are shown at higher magnification by electron microscopy in Figure B. Here, each Acinus appears as a grape-shaped cluster of cells with a centrally located lumen (L). The Acinus is lined by a row of cells that vary in height from cuboidal to low columnar. The size and shape of the secretory cells can vary considerably. Their structure depends on their secretory activity, which, in turn, is strongly influenced by levels of testosterone in the circulating blood.
The nuclei of the secretory cells in Figures A and B (N) occupy the base of the cell. The apical pole of the cell, in most cases, is filled with clear, round secretory vesicles (V), The “empty” appearance of the secretory vesicles suggests that their contents were extracted during specimen preparation. Because fatty or oily substances are frequently extracted by the organic solvents utilized in specimen preparation, and because Prostaglandins are long-chain hydroxy fatty acids, it seems likely that the “empty” vesicles may, in life, have been filled with material rich in Prostaglandins.
Many Smooth Muscle fibers (SM) are evident in the connective tissue surrounding the tubuloacinar glands. At the moment of ejaculation, these Smooth Musclefibers, which are under the control of the autonomic nervous system, are stimulated to contract, thus forcing Prostatic Fluid out of the acini, into the ducts of the glands, and out into the Urethra. Here, Prostatic Fluid mixes with spermatozoa delivered by the Vas Deferens and fluid secreted by the seminal vesicles to form Semen.
Plate 17-3, Figures A and B. Matched pair of light and electron micrographs of serial thick and thin sections of the Prostate Gland of the squirrel monkey. C, prostatic concretion; G, Acinus of tubuloacinar gland; L, lumen of Acinus; N, Nucleus of secretory cell; S, fibromuscular stroma; SM, Smooth Muscle; V, secretory vesicles in apical pole of secretory cell. Figure A, 700 X; Figure B, 1,100 X
The seminal vesicles are a pair of highly infolded, saclike bodies, each about 5 cm long, that empty their contents into the Vas Deferens near the point at which the Vas Deferens joins the Urethra. Spermatozoa depend on the hydrolysis of ATP for their motility, and the seminal vesicles contribute to the Semen a yellow, viscous, sticky fluid rich in Fructose. Fructose, a substrate for the biochemical production of ATP, serves as fuel for swimming spermatozoa suspended in Semen. The ATPrequired by the sperm Flagellum is generated largely by the elongated Mitochondria wound around the flagellar Axoneme in the vicinity of the midpiece of the sperm (see Figure 17-1). Hence, the contribution of the seminal vesicles to the Seminal Fluid is of considerable physiologic importance.
Figure A is a light micrograph of a section taken through the Seminal Vesicle of a squirrel monkey. Here, the lumen (L) is divided into a number of compartments by the extensively folded Mucosa. The Mucosa of the Seminal Vesicle consists of a pseudostratified epithelium that rests on a bed of loose connective tissue (Co). The pseudostratified epithelium consists of either cuboidal or columnar epithelial cells (E) and small, round Basal Cells (arrowhead). The Basal Cells are so small that they are difficult to detect at this magnification. The structure of the epithelium of the Seminal Vesicle depends on a number of variables, including the hormonal status and the age of the individual. Under conditions of high testosterone, the cells tend to enlarge and become columnar. When testosterone levels fall, the cells become less active and shrink, becoming cuboidal. Consequently, histologic sections of seminal vesicles derived from different individuals may exhibit considerable variations in epithelial microanatomy.
Figure B is a matching electron micrograph of a serial thin section taken through the same Seminal Vesicle depicted in Figure A. In this image, the star-shaped lumen (L) is bordered by many folds of the Mucosa. Although the epithelium appears to be simple cuboidal at first glance, close study reveals the presence of small Basal Cells (arrowhead) next to the Basement Membrane. The small, round Basal Cells are squeezed in between the bases of the larger cuboidal cells (E), thus placing the epithelium in the pseudostratified category. The cuboidal epithelial cells contain several kinds of cytoplasmic inclusions evident at this relatively low magnification, including pigment granules (arrow) and secretory vesicles (S). The epithelium is supported by loose connective tissue that contains Collagen fibrils (Co) and elastic fibers (which require special stains to be seen). A number of small capillaries (C) and nerve fibers pass through the network of connective tissue that supports the epithelium. The Mucosa lies on top of a thick layer of Smooth Muscle(not shown in these micrographs) that contracts during ejaculation, thus squeezing the contents of the seminal vesicles out into the Vas Deferens, which, in turn, carries the fluid out into the Urethra during ejaculation.
Plate 17-5, Figures A and B. Matched pair of light and electron micrographs of serial thick and thin sections taken through the Seminal Vesicle of the squirrel monkey. C, capillary; Co, Collagen fibrils; E, cuboidal epithelial cells; L, lumen; S, secretory vesicles in apical portion of cuboidal epithelial cell; arrow (Figure B), pigment granules; arrowhead, basal cell. 800 X