Histology_Ross

Histology_Ross.  Golgi phase. This phase is characterized by the presence of in the multiple Golgi complexes of the spermatid. These two pairs of homologous chromosomes G1 phase G2 phase *note: prophase II, anaphase II, and telophase II are not shown ovum FIGURE 22.10 • Comparison of mitosis and meiosis in a spermatogonial cell. The two pairs of chromosomes (2n) of maternal and paternal origin are depicted in red and blue, respectively. The mitotic division produces daughter cells that are genetically identical to the parental (2n) cell. The meiotic division, which has two components, a reductional division and an equatorial division, produces a cell that has only half the number of chromosomes (n). In addition, during the chromosome pairing in prophase I of meiosis, chromosome segments are exchanged, crossing-over, creating genetic diversity. In humans, the first polar body does not divide, but it does so in other species. *Note that prophase II, anaphase II, and telophase II are not shown.


Histology_Ross

Histology_Ross. Golgi acrosomal vesicle acrosome manchette flagellum centriole sheath FIGURE 22.11 • Schematic diagram of spermiogenesis in the human. The basic changes in the structure of the key organelles of the spermatid are illustrated (see text for detailed explanation). (Modified from Dym M. In: Weiss L, ed. Cell and Tissue Biology: A Textbook of Histology, 6th ed. Baltimore: Urban & Schwarzenberg, 1988.) proacrosomal granules, rich in glycoproteins, coalesce into a membrane-bounded vesicle, the acrosomal vesicle, adjacent to the nuclear envelope. The vesicle enlarges and its contents increase during this phase. The position of the acrosomal vesicle determines the anterior pole of the developing sperm. Also during this phase, the centrioles migrate from the juxtanuclear region to the posterior pole of the spermatid, where the mature centriole aligns at right angles to the plasma membrane. The centriole initiates the assembly of the nine peripheral microtubule doublets and two central


Histology_Ross

Histology_Ross. pole of the spermatid, where the mature centriole aligns at right angles to the plasma membrane. The centriole initiates the assembly of the nine peripheral microtubule doublets and two central micro-tubules that constitute the axoneme of the sperm tail.


Histology_Ross

Histology_Ross.  Cap phase. In this phase, the acrosomal vesicle spreads over the anterior half of the nucleus. This reshaped structure is called the acrosomal cap. The portion of the nuclear envelope beneath the acrosomal cap loses its pores and becomes thicker. The nuclear contents also condense.  Acrosome phase. In this phase, the spermatid reorients itself so that the head becomes deeply embedded in the Sertoli cell and points toward the basal lamina. The developing flagellum extends into the lumen of the seminiferous tubule. The condensed nucleus of the spermatid flattens and elongates, the nucleus and its overlying acrosome also move to a position immediately adjacent to the anterior plasma membrane, and the cytoplasm is displaced posteriorly. The cytoplasmic microtubules become organized into a cylindrical sheath, the manchette, which extends from the posterior rim of the acrosome toward the posterior pole of the spermatid.


Histology_Ross

Histology_Ross. The centrioles, which had earlier initiated the development of the flagellum, now move back to the posterior surface of the nucleus where the immature centriole becomes attached to a shallow groove in the nucleus. They are then modified to form the connecting piece, or neck region, of the developing sperm. Nine coarse fibers develop from the centrioles attached to the nucleus and extend into the tail as the outer dense fibers peripheral to the microtubules of the axoneme. These fibers unite the nucleus with the flagellum; hence, the name connecting piece.


Histology_Ross

Histology_Ross. As the plasma membrane moves posteriorly to cover the growing fagellum, the manchette disappears, and the mitochondria migrate from the rest of the cytoplasm to form a tight, helically wrapped sheath around the coarse fibers in the neck region and its immediate posterior extension (Fig. 22.12). This region is the middle piece of the tail of the sperm. Distal to the middle piece, a fbrous sheath consisting of two longitudinal columns and numerous connecting ribs surrounds the nine longitudinal fibers of the principal piece and extends nearly to the end of the flagellum. This short segment of the tail distal to the fibrous sheath is called the end piece.  Maturation phase. This last phase of spermatid remodel ing reduces excess cytoplasm from around the flagella to form mature spermatozoon. The Sertoli cells then phagocytose this excess cytoplasm, also termed the resid ual body. The intercellular bridges that have characterized the developing gametes since the prespermatocyte stages


Histology_Ross

Histology_Ross. The Sertoli cells then phagocytose this excess cytoplasm, also termed the resid ual body. The intercellular bridges that have characterized the developing gametes since the prespermatocyte stages remain with the residual bodies. Spermatids are no longer attached to each other and are released from the Sertoli cells.


Histology_Ross

Histology_Ross. Spermatids are released into the lumen of the seminiferous tubules during the process called spermiation. Toward the end of maturation phase of spermatogenesis, elongated spermatids are released from Sertoli cells into the lumen of seminiferous tubule. This complex process, called spermiation involves progressive removal of specialized Sertoli-to-spermatid junctional complexes and disengagement of spermatids from the Sertoli cell. The presence of the 1-integrins in the Sertoli-to-spermatid junctions, as well as increased activity of the integrin-linked kinase at the time of spermiation, suggests an enzymatic control of spermatid release. The rate of spermiation in the testis determines the number of sperm cells in the ejaculate of semen. Various pharmacologic treatments, toxic agents, and gonadotropin suppression result in spermiation failure, in which spermatids are not released but instead are retained and phagocytosed by the Sertoli cell. Structure of the Mature Sperm


Histology_Ross

Histology_Ross. Structure of the Mature Sperm The events of spermiogenesis result in a structurally unique cell. The mature human sperm is about 60 m long. The sperm head is flattened and pointed and measures 4.5 m long by 3 m wide by 1 m thick (see Fig. 22.12). The acrosomal cap that covers the anterior two-thirds of the nucleus contains hyaluronidase, neuraminidase, acid phosphatase, and a trypsin-like protease called acrosin. These acrosomal enzymes are essential for penetration of the zona pellucida of the outer dense fibers 4, 5, 6 outer doublets of axonemal complex central pair of microtubules of axonemal complex FIGURE 22.12 • Diagram of a human spermatozoon. Regions of the spermatozoon are indicated on the left. Key structural features of the head (viewed in frontal and sagittal planes), the middle piece, and the principal piece of the spermatozoon are illustrated on the right. (Modified from Pederson PL, Fawcett DW. In: Hafez ESE, ed. Human Semen and Fertility Regulation in the


Histology_Ross

Histology_Ross. Male. St. Louis: CV Mosby, 1976.) ovum. The release of acrosomal enzymes as the sperm touches the egg is the first step in the acrosome reaction. This complex process facilitates sperm penetration and subsequent fertilization and prevents the entry of additional sperm into the ovum. The sperm tail is subdivided into the neck, the middle piece, the principal piece, and the end piece. The short neck contains the centrioles and the origin of the coarse fibers. The middle piece is approximately 7 m long and contains the mitochondria, helically wrapped around the coarse fibers and the axonemal complex. These mitochondria provide the energy for movement of the tail and thus are responsible for the motility of the sperm. The principal piece is approximately 40 m long and contains the fibrous sheath external to the coarse fibers and the axonemal complex. The end piece, approximately the last 5 m of the flagellum in the mature sperm, contains only the axonemal complex.


Histology_Ross

Histology_Ross. Newly released sperm cells are processed in the epididymidis where they acquire motility and undergo further maturation.


Histology_Ross

Histology_Ross. Newly released sperm cells are nonmotile and are carried from the seminiferous tubules in a fluid secreted by the Sertoli cells. The fluid and sperm flow through the seminiferous tubules, facilitated by peristaltic contractions of the peritubular contractile cells of the lamina propria. They then enter the straight tubules, a short segment of the seminiferous tubule where the epithelium consists only of Sertoli cells. At the mediastinum testis, the fluid and sperm enter the rete testis, an anastomosing system of ducts lined by simple cuboidal epithelium (Plate 87, page 820). From the rete testis, they move into the extratesticular portion of the efferent ductules (ductuli efferentes), the first part of the excurrent duct system, and then into the proximal portion of the duct of the epididymis (ductus epididymis). As the sperm cells move through the 4 to 5 m of the highly coiled duct of the epididymis, they acquire motility and undergo several maturational changes,. These changes


Histology_Ross

Histology_Ross. (ductus epididymis). As the sperm cells move through the 4 to 5 m of the highly coiled duct of the epididymis, they acquire motility and undergo several maturational changes,. These changes include  condensation of nuclear DNA. The head of the sperm decreases in size.  further reduction of cytoplasm. The sperm cells become more slender.  changes in plasma membrane lipids, proteins, and glycosy lation.  alterations in the outer acrosomal membrane (decapacita tion). The surface-associated decapacitation factor is added to inhibit the fertilizing ability of the sperm cells (page 803).


Histology_Ross

Histology_Ross. Initiation of sperm cell motility during cell transit through the epididymis is most likely related to changes in the intracellular levels of cyclic adenosine monophosphate (cAMP), calcium ions (Ca2 ), and intracellular pH. These factors regulate flagellar activity through changes in protein phosphorylation, resulting from activities of protein kinases and protein phosphatases. For instance, pharmacologic stimulation of protein kinase A activity increases motility of sperm cells, whereas inhibition of protein phosphatase activity may initiate or stimulate such motility. This suggests that phosphatases have an important role in the regulation of sperm kinetic activity. Contractions of the smooth muscle that surrounds the progressively distal and larger ducts continue to move the sperm by peristaltic action until they reach the distal portion of the duct of the epididymis, where they are stored before ejaculation.


Histology_Ross

Histology_Ross. Sperm can live for several weeks in the male excurrent duct system, but they will survive only 2 to 3 days in the female reproductive tract. They acquire the ability to fertilize the ovum only after some time in the female tract. This process, which involves removal and replacement of glycocalyx components (glycoconjugates) on the sperm membrane, is called capacitation. Capacitation of spermatozoa is described in detail in Chapter 23 (page 840). Cycle of the Seminiferous Epithelium


Histology_Ross

Histology_Ross. Cycle of the Seminiferous Epithelium Differentiating spermatogenic cells are not arranged at random in the seminiferous epithelium; specific cell types are grouped together. These groupings or associations occur because intercellular bridges are present between the progeny of each pair of type Ap spermatogonia and because the synchronized cells spend specific times in each stage of maturation. All phases of differentiation occur sequentially at any given site in a seminiferous tubule as the progeny of stem cells remain connected by cytoplasmic bridges and undergo synchronous mitotic and meiotic divisions and maturation (see Fig. 22.10).


Histology_Ross

Histology_Ross. Each recognizable grouping, or cell association, is considered a stage in a cyclic process. The series of stages that appears between two successive occurrences of the same cell association pattern at any given site in the seminiferous tubule constitutes a cycle of the seminiferous epithelium. The cycle of the seminiferous epithelium has been most thoroughly studied in rats, in which 14 successive stages occur in linear sequence along the tubule. In man, six stages or cell associations are defined in the cycle of the seminiferous epithelium (Fig. 22.13). These stages are not as clearly delineated as those in rodents because in man the cellular associations occur in irregular patches that form a mosaic pattern. Duration of spermatogenesis in humans is approximately 74 days.


Histology_Ross

Histology_Ross. After injecting a pulse of tritiated thymidine, a specific generation of cells can be followed by sequential biopsies of the seminiferous tubules. In this way, the time required for the labeled cells to go through the various stages can be determined. Several generations of developing cells may be present in the thickness of the seminiferous epithelium at any given site and at any given time, which produces the characteristic cell associations. Autoradiographic studies have revealed that the duration of the cycle of the seminiferous epithelium is constant, lasting about 16 days in humans. In humans it would require about 4.6 cycles (each 16 days long), or approximately 74 days, for a spermatogonium produced by a stem cell to complete the process of spermatogenesis. It would then require approximately 12 days for the spermatozoon to pass through the epididymis. Approximately 300 million sperm cells are produced daily in the human testis. The length of the cycle and the time required


Histology_Ross

Histology_Ross. approximately 12 days for the spermatozoon to pass through the epididymis. Approximately 300 million sperm cells are produced daily in the human testis. The length of the cycle and the time required for spermatogenesis are constant and specific in each species. Therefore, in any pharmacologic intervention (e.g., therapy for male infertility), if a drug is given that affects the initial phases of spermatogenesis, approximately 86 days are required to see the effect of that compound on sperm production.


Histology_Ross

Waves of the Seminiferous Epithelium

Histology_Ross. Waves of the Seminiferous Epithelium


Histology_Ross

Histology_Ross. As indicated above, the cycle of the seminiferous epithelium describes changes that occur with time at any given site in the tubule. In addition, the wave of the seminiferous epithelium describes the distribution of patterns of cellular association (stages) along the length of the tubule. In rodents and other mammals that have been studied, including subhuman primates, each stage occupies a significant length of the seminiferous tubule, and the stages appear to occur sequentially along the length of the tubule. In the rat, there are approximately 12 waves in each tubule. A transverse section through the tubule usually reveals only one pattern of cell associations. There are no waves in the human seminiferous epithelium. Each pattern of cellular associations (stage of the cycle) has a patch-like distribution in the human seminiferous tubule (Fig. 22.14). Patches do not extend around the circumference of the tubule, nor are they in sequence. Therefore, a transverse section through a


Histology_Ross

Histology_Ross. distribution in the human seminiferous tubule (Fig. 22.14). Patches do not extend around the circumference of the tubule, nor are they in sequence. Therefore, a transverse section through a human seminiferous tubule may reveal as many as six different stages of the cycle arranged in a pie-wedge fashion around the circumference of the tubule.


Histology_Ross

Histology_Ross. FIGURE 22.13 • Schematic drawing of the stages of the human seminiferous epithelium. This diagram shows each of the six recognizable cell associations that occur in the cycle of the human seminiferous epithelium. Sa, Sb, Sc, and Sd indicate spermatids in various steps of differentiation. (Based on Clermont Y. The cycle of the seminiferous epithelium in man. Am J Anat 1963;112:50.) FIGURE 22.14 • Diagram of organization of seminiferous epithelium in humans and other species. a. In subhuman species, a particular cellular association occupies varying lengths along the tubule. Therefore, in a typical cross section only a single cellular association is observed. b. In humans, cellular associations occur in irregularly shaped areas along the tubule, and therefore, a cross section typically shows two or more cellular associations. (Modified from Dym M. In: Weiss L, ed. Cell and Tissue Biology: A Textbook of Histology, 6th ed. Baltimore: Urban & Schwarzenberg, 1988.)


Histology_Ross

Histology_Ross. Sertoli cells constitute the true epithelium of the seminiferous epithelium. Sertoli cells (sustentacular cells) are tall, columnar, non-replicating epithelial cells that rest on the thick, multilayered basal lamina of the seminiferous epithelium (Fig. 22.15). They are the supporting cells for the developing sperm that attach to their surface after meiosis. Sertoli cells contain an extensive sER, a well-developed rER, and stacks of annulate lamellae. They have numerous spherical and elongated mitochondria, a well-developed Golgi apparatus, and varying numbers of microtubules, lysosomes, lipid droplets, vesicles, glycogen granules, and filaments. A sheath of 7to 9-nm filaments surrounds the nucleus and separates it from other cytoplasmic organelles.


Histology_Ross

Histology_Ross. The euchromatic Sertoli cell nucleus, a reflection of this very active cell, is generally ovoid or triangular and may have one or more deep infoldings. Its shape and location vary. It may be flattened, lying in the basal portion of the cell near and parallel to the base of the cell, or it may be triangular or ovoid, lying near or some distance from the base of the cell. In some species, the Sertoli cell nucleus contains a unique tripartite structure that consists of an RNA-containing nucleolus flanked by a pair of DNA-containing bodies called karyosomes (Fig. 22.16).


Histology_Ross

Histology_Ross. In man, characteristic inclusion bodies (of Charcot-Btcher) are found in the basal cytoplasm. These slender fusiform crystalloids measure 10 to 25 m long by 1 m wide and are visible in routine histologic preparations. With transmission electron microscopy, they are resolved as bundles of poorly ordered, parallel or converging, straight, dense 15-nmdiameter filaments (see Fig. 22.15). Their chemical composition and function are unknown; however, recent studies detected an accumulation of lipoprotein receptor (CLA-1) proteins. This suggests that inclusion bodies might be involved in lipids transport and their utilization by the Sertoli cells. FIGURE 22.15 • Electron micrograph of a human Sertoli cell.


Histology_Ross

Histology_Ross. FIGURE 22.15 • Electron micrograph of a human Sertoli cell. This electron micrograph shows characteristic crystalloid inclusion bodies of Charcot-Btcher in the basal cytoplasm of the Sertoli cell. The basal lamina (BL) is indicated for orientation. 9,000. Inset. This higher magnification shows filaments of the crystalloid. 27,000. (Courtesy of Dr. Don F. Cameron.) The Sertoli cell–to–Sertoli cell junctional complex consists of a structurally unique combination of membrane and cytoplasmic specializations.


Histology_Ross

Histology_Ross. The Sertoli cell–to–Sertoli cell junctional complex consists of a structurally unique combination of membrane and cytoplasmic specializations. Sertoli cells are bound to one another by an unusual Sertoli cellto-Sertoli cell junctional complex (Fig. 22.17). This complex is characterized, in part, by an exceedingly tight junction (zonula occludens) that includes more than 50 parallel fusion lines in the adjacent membranes. In addition, two cytoplasmic components characterize this unique junctional complex:  A fattened cisterna of sER lies parallel to the plasma membrane in the region of the junction in each cell. Actin flament bundles, hexagonally packed, are inter posed between the sER cisternae and the plasma membranes.


Histology_Ross

Histology_Ross. FIGURE 22.16 • Schematic drawing of the Sertoli cell and its relationship to adjacent spermatogenic cells. This drawing shows the Sertoli–to–Sertoli junctional specialization between adjacent Sertoli cells and the Sertoli–to–spermatid junctional specialization between the Sertoli cell and late spermatids. The Sertoli–to–Sertoli junctional complex is an adhesion device that includes a tight junction that contributes to the blood–testis barrier. The junctional specialization between the Sertoli cell and late spermatids residing in deep recesses within the apical cytoplasm is an adhesion device only. Lateral processes of the Sertoli cells extend over the surface of the spermatocytes and spermatids. Note the ultrastructural features of the Sertoli cell, including the microtubule arrays and characteristic shape of the nucleus and its karyosome. (Reprinted with permission from Bloom W, Fawcett DW. A Textbook of Histology. Philadelphia: WB Saunders, 1975.)


Histology_Ross

Histology_Ross. Philadelphia: WB Saunders, 1975.) A similar-appearing junctional complex in the Sertoli cell is also present at the site where the spermatids are attached. However, no tight junction is present, and the spermatid lacks flattened cisternae of sER and actin filament bundles (see Figs. 22.16 and 22.17). Other junctional specializations of the Sertoli cells include gap junctions between Sertoli cells, desmosome-like junctions between Sertoli cells and early-stage spermatogenic cells, and hemidesmosomes at the Sertoli cell–basal lamina interface. The Sertoli cell–to–Sertoli cell junctional complex divides the seminiferous epithelium into basal and luminal compartments.


Histology_Ross

Histology_Ross. The Sertoli cell–to–Sertoli cell junctions establish two epithelial compartments, a basal epithelial compartment and a luminal compartment. Spermatogonia and early primary spermatocytes are restricted to the basal compartment (i.e., between the Sertoli cell–to–Sertoli cell junctions and the basal lamina). More mature spermatocytes and spermatids are restricted to the luminal side of the Sertoli cell–to–Sertoli cell junctions. Early spermatocytes produced by mitotic division of type B spermatogonia must pass through the junctional complex to move from the basal compartment to the luminal compartment. This movement occurs via the formation of a new junctional complex between Sertoli cell processes that extend beneath the newly formed spermatocytes, followed by the breakdown of the junction above them. Thus, in the differentiation of the spermatogenic cells, the processes of meiosis and spermiogenesis occur in the luminal compartment.


Histology_Ross

Histology_Ross. In both compartments, spermatogenic cells are surrounded by complex processes of the Sertoli cells. Because of the unusually close relationships between Sertoli cells and differentiating spermatogenic cells, it has been suggested that Sertoli cells serve as “nurse,” or supporting, cells (i.e., they function in the exchange of metabolic substrates and wastes between the developing spermatogenic cells and the circulatory system). In addition, Sertoli cells phagocytose and break down the residual bodies formed in the last stage of spermiogenesis. They also phagocytose any spermatogenic cells that fail to differentiate completely. The Sertoli cell–to–Sertoli cell junctional complex is the site of the blood–testis barrier. In addition to the physical compartmentalization described above, the Sertoli cell–to–Sertoli cell junctional complex also FIGURE 22.17 • Electron micrograph of Sertoli cell junctions.


Histology_Ross

Histology_Ross. This electron micrograph demonstrates a Sertoli–to–Sertoli junctional complex and, in close proximity, a Sertoli–to–spermatid junctional specialization. Condensation and shaping of the spermatid nucleus (N) are well advanced. The acrosome (A) of the spermatid appears as a V-shaped profile, and in close association with it is the Sertoli cell junctional specialization characterized by bundles of microfilaments that are cut in cross section (arrows). The associated profile of endoplasmic reticulum resides immediately adjacent to the microfilament bundles. The Sertoli–to–Sertoli junction lies below, joining one Sertoli cell (S1) to the adjacent Sertoli cell (S2). The arrowheads indicate the limits of the junction. Note that the junction here reveals the same elements, the microfilament bundles (arrows) and a profile of endoplasmic reticulum, as are seen in the Sertoli–to–spermatid junctional specialization. Not evident at this magnification is the tight junction associated with the


Histology_Ross

Histology_Ross. bundles (arrows) and a profile of endoplasmic reticulum, as are seen in the Sertoli–to–spermatid junctional specialization. Not evident at this magnification is the tight junction associated with the Sertoli–to–Sertoli junctional complex. 30,000.


Histology_Ross

Histology_Ross. creates a permeability barrier called the blood–testis barrier. This barrier is essential in creating a physiologic compartmentalization within the seminiferous epithelium with respect to ionic, amino acid, carbohydrate, and protein composition. Therefore, the composition of the fluid in the seminiferous tubules and excurrent ducts differs considerably from the composition of the blood plasma and testicular lymph. Plasma proteins and circulating antibodies are excluded from the lumen of the seminiferous tubules. The exocrine secretory products of the Sertoli cells (particularly the androgen-binding protein (ABP), which has a high binding affinity for testosterone and DHT) are highly concentrated in the lumen of the seminiferous tubules and maintain a high concentration of testosterone, which provides a favorable microenvironment for the differentiating spermatogenic cells.


Histology_Ross

Histology_Ross. Most important, the blood–testis barrier isolates the genetically different and therefore antigenic haploid germ cells (secondary spermatocytes, spermatids, and sperm) from the immune system of the adult male. Antigens produced by, or specific to, the sperm are prevented from reaching the systemic circulation. Conversely, -globulins and specific sperm antibodies found in some individuals are prevented from reaching the developing spermatogenic cells in the seminiferous tubule (Folder 22.3). Therefore, the blood–testis barrier serves an essential role in isolating the spermatogenic cells from the immune system. Sertoli cells have both exocrine and endocrine secretory functions.


Histology_Ross

Histology_Ross. Sertoli cells have both exocrine and endocrine secretory functions. In addition to secreting fluid that facilitates passage of the maturing sperm along the seminiferous tubules to the intratesticular ducts, Sertoli cells produce critical factors necessary for the successful progression of spermatogonia into spermatozoa. They secrete a 90-kilodalton androgen-binding protein (ABP). ABP concentrates testosterone in the luminal compartment of the seminiferous tubule, where high concentrations of testosterone are essential for normal maturation of the developing sperm.


Histology_Ross

Histology_Ross. FSH and testosterone receptors are present on Sertoli cells; therefore, their secretory function is regulated by both FSH and testosterone (Fig. 22.18). Sertoli cells secrete several endocrine substances, such as inhibin, a 32-kilodalton glycoprotein hormone involved in the feedback loop that inhibits follicle-stimulating hormone (FSH) release from the anterior pituitary gland. In addition, Sertoli cells synthesize plasminogen activator, which converts plasminogen to the active proteolytic hormone plasmin, transferrin (an iron-transporting protein), and ceruloplasmin (a copper-transporting protein). Furthermore, the Sertoli cells secrete other glycoproteins that function as growth factors or paracrine factors, such as the Mlerian-inhibiting factor (MIF), stem cell factor (SCF), and glial cell line-derived neurotrophic factor (GDNF).


Histology_Ross

Histology_Ross. At the end of each seminiferous tubule there is an abrupt transition to the straight tubules, or tubuli recti. This short terminal section of the seminiferous tubule is lined only by Sertoli cells (Plate 87, page 820). Near their termination, the straight tubules narrow, and their lining changes to a simple cuboidal epithelium. The straight tubules empty into the rete testis, a complex series of interconnecting channels within the highly vascular connective tissue of the mediastinum (Fig. 22.19). A simple cuboidal or low columnar epithelium lines the channels of the rete testis. These cells have a single apical cilium and relatively few short apical microvilli.


Histology_Ross

Histology_Ross. logic importance of the blood–testis barrier:  Spermatozoa and spermatogenic cells possess molecules that are unique to these cells and are recognized as “foreign” (not self) by the immune system.  Spermatozoa are first produced at puberty, long after the individual has become immunocompetent (i.e., capa-ble of recognizing foreign molecules and producing an-tibodies against them). Failure of the spermatogenic cells and spermatozoa to remain isolated results in the production of sperm-specific seen after vasectomy and in some cases of infertility. After vasectomy, sperm-specific antibodies are pro-duced as the cells of the immune system are exposed to the spermatozoa that may leak from the severed ductus deferens. Thus, sperm no longer remain isolated from the immune system within the reproductive tract. In some cases of infertility, sperm-specific antibodies have been found in the semen. These antibodies cause the sperm to agglutinate, preventing movement and interaction with the


Histology_Ross

Histology_Ross. reproductive tract. In some cases of infertility, sperm-specific antibodies have been found in the semen. These antibodies cause the sperm to agglutinate, preventing movement and interaction with the ovum.


Histology_Ross

Histology_Ross.  FOLDER 22.3 Clinical Correlation: Sperm-Specific Antigens and the Immune Response Two basic facts are well established about the immuno-antibodies. Such an immune response is sometimes The excurrent duct system develops from the mesonephric (Wolffian) duct and mesonephric tubules.


Histology_Ross

Histology_Ross. The excurrent duct system develops from the mesonephric (Wolffian) duct and mesonephric tubules. The initial development of Leydig cells and initiation of testosterone secretion stimulate the mesonephric (Wolffian) duct to differentiate into the excretory duct system for the developing testis (Fig. 22.20). The portion of the mesonephric duct adjacent to the developing testis becomes convoluted and differentiates into the duct of the epididymis. In addition, a number (about 20) of the remaining mesonephric tubules in this region make contact with the developing seminiferous cords and finally develop into the efferent ductules (Fig. 22.21 and Plate 88, page 822). They connect the developing rete testis with the duct of the epididymis. The distal part of the mesonephric duct acquires a thick, smooth muscle coat and becomes the ductus deferens. The end of the distal mesonephric duct gives rise to the ejaculatory duct and seminal vesicles.


Histology_Ross

Histology_Ross. The efferent ductules are lined with pseudostratified columnar epithelium. In man, approximately 20 efferent ductules connect the channels of the rete testis at the superior end of the mediastinum to the proximal portion of the duct of the epididymis. As the efferent ductules exit the testis, they become highly coiled and form 6 to 10 conical masses, the coni vasculosi, whose bases form part of the head of the epididymis. The coni vasculosi, each about 10 mm in length, contain the highly convoluted ducts that measure 15 to 20 cm in length. At the base of the cones, the efferent ducts open into a single channel, the duct of the epididymis (see Fig. 22.4).


Histology_Ross

Histology_Ross. The efferent ductules are lined with a pseudostratified columnar epithelium that contains clumps of tall and short cells, giving the luminal surface a sawtooth appearance (see Fig. 22.21). Interspersed among the columnar cells are occasional basal cells that serve as epithelial stem cells. The tall columnar cells are ciliated. The short nonciliated cells have numerous microvilli and canalicular invaginations of the apical surface as well as numerous pinocytotic vesicles, membrane-bounded dense bodies, lysosomes, and other cytoplasmic structures associated with endocytotic activity. Most of the fluid secreted in the seminiferous tubules is reabsorbed in the efferent ductules.


Histology_Ross

Histology_Ross. Most of the fluid secreted in the seminiferous tubules is reabsorbed in the efferent ductules. A smooth muscle layer in the excurrent ducts first appears at the beginning of the efferent ductules. The smooth muscle cells form a layer several cells thick in which the cells are arrayed as a circular sheath in the wall of the ductule. Interspersed among the muscle cells are elastic fibers. Transport of the sperm in the efferent ductules is affected largely by both ciliary action and contraction of this fibromuscular layer. The epididymis is an organ that contains the efferent ductules and the duct of the epididymis.


Histology_Ross

Histology_Ross. The epididymis is a crescent-shaped structure that lies along the superior and posterior surfaces of the testis. It measures about 7.5 cm in length and consists of the efferent ductules and the duct of the epididymis and associated vessels, smooth muscles, and connective tissue coverings (Fig. 22.22 and Plate 88, page 822). The duct of the epididymis is a highly coiled tube measuring 4 to 6 m in length. The epididymis is divided into a head, a body, and a tail (see Fig. 22.4). The efferent ductules occupy the head, and the duct of the epididymis occupies the body and tail. Newly produced sperm, which enter the epididymis from the testis, mature during their passage through the duct of the epididymis, acquiring motility and the ability to fertilize an oocyte. During this androgen-dependent maturation process, the head of the sperm is modified by the addition of surface-associated decapacitation factor containing epididymal fluid glycoconjugates. This process, called decapacitation,


Histology_Ross

Histology_Ross. maturation process, the head of the sperm is modified by the addition of surface-associated decapacitation factor containing epididymal fluid glycoconjugates. This process, called decapacitation, inhibits the fertilizing ability of the sperm in a reversible inhibitory adenohypophysis testosterone stimulatory GnRH-like peptides spermatogenic cells Leydig cells Sertoli cells ? hypothalamus other CNS centers GnRH FSH LH prolactin inhibin estradiol DHT


Histology_Ross

Histology_Ross. FIGURE 22.18 • Diagram depicting the hormonal regulation of male reproductive function. Blue arrows indicate stimulatory action on the system; red arrows indicate inhibitory feedback. See text for explanation.


Histology_Ross

Histology_Ross. FIGURE 22.19 • Photomicrograph of human testis. a. This H&E–stained specimen shows the site that includes the mediastinum of the testis. On the right are seminiferous tubules, and on the left are the anastomosing channels of the rete testis. The arrow indicates termination of a straight tubule that is lined only by Sertoli cells. It is at this site that the tubule content enters the rete testis and the channels are then lined by a simple cuboidal epithelium. 70. b. This higher magnification from a slightly deeper section of the same specimen shows the rete testis (left), a cross section of a seminiferous tubule (upper right), and a terminating straight tubule (asterisk) where it is entering the rete testis. Note the abrupt change in the epithelial lining at this site. As noted, the lining epithelium of the rete testis is simple cuboidal. 275.


Histology_Ross

Histology_Ross. extend from the luminal surface of the principal cells (Plate 88, page 822). The stereocilia vary in height from 25 m in the head to approximately 10 m in the tail.  Basal cells that represent small, round cells resting on the basal lamina. They are the stem cells of the duct epithelium. In addition, migrating lymphocytes called halo cells are often found within the epithelium. Under normal conditions, the epithelium of the epididymis represents the most proximal level of the excurrent duct system in which lymphocytes are present. Epididymal cells function in both absorption and secretion.


Histology_Ross

Histology_Ross. Epididymal cells function in both absorption and secretion. Most of the fluid that is not reabsorbed by the efferent ductules is reabsorbed in the proximal portion of the epididymis. The epithelial cells also phagocytose any residual bodies not removed by the Sertoli cells as well as sperm that degenerate in the duct. The apical cytoplasm of the principal cells contains numerous invaginations at the bases of the stereocilia, along with coated vesicles, multivesicular bodies, and lysosomes (Fig. 22.24). The principal cells secrete glycerophosphocholine, sialic acid, and glycoproteins, which, in addition to the glycocalyx and steroids, aid in the maturation of the sperm. They have numerous cisternae of rER surrounding the basally located nucleus and a remarkably large supranuclear Golgi apparatus. Profiles of sER and rER are also present in the apical cytoplasm. The smooth muscle coat of the duct of the epididymis gradually increases in thickness to become three-layered in the tail.


Histology_Ross

Histology_Ross. The smooth muscle coat of the duct of the epididymis gradually increases in thickness to become three-layered in the tail. In the head of the epididymis and most of the body, the smooth muscle coat consists of a thin layer of circular smooth muscle resembling that of the efferent ductules. In the tail, inner and outer longitudinal layers are added. These three layers are then continuous with the three smooth muscle layers of the ductus deferens, the next component of the excurrent duct system (Plate 89, page 824).


Histology_Ross

Histology_Ross. Differences in smooth muscle function parallel these morphologic differences. In the head and body of the epididymis, spontaneous, rhythmic peristaltic contractions serve to move the sperm along the duct. Few peristaltic contractions occur in the tail of the epididymis, which serves as the principal reservoir for mature sperm. These sperm are forced into the ductus deferens by intense contractions of the three smooth muscle layers after appropriate neural stimulation associated with ejaculation.


Histology_Ross

Histology_Ross. FIGURE 22.20 • Schematic diagram of development of intratesticular and excurrent duct systems. a. This diagram shows the testis in the seventh week of development before it descends into the scrotal sac. Note that the mesonephric duct and its tubules give rise to the excurrent duct system for the developing testis. b. Sagittal section of a fully developed testis positioned within the scrotum. Note that the seminal vesicles, ejaculatory ducts, ductus deferens, epididymis, and efferent ductules are all developed from the mesonephric duct and tubules. The seminiferous tubules, straight tubules, and rete testis develop from the indifferent gonads. The prostate gland develops from the prostatic primordium that originates from the pelvic urethra.


Histology_Ross

Histology_Ross. FIGURE 22.21 • Photomicrograph of efferent ductules. The specimen in this photomicrograph was stained with picric acid and hematoxylin to better visualize the epithelial components of the efferent ductules. The efferent ductules are lined by pseudostratified columnar epithelium. The luminal surface has an uneven or wavy appearance because of the presence of alternating groups of tall columnar cells and cuboidal cells. The ductules are surrounded by several layers of circularly arranged smooth muscle (SM). Within the ductule lumina are clumped spermatozoa (asterisks). Connective tissue (CT ) makes up the stroma of the organ and contains blood vessels (BV ) of various sizes. 120. Inset. This higher magnification of the pseudostratified epithelium shows columnar and cuboidal cells that contain sparse cilia. 500.


Histology_Ross

Histology_Ross. FIGURE 22.22 • Photomicrograph of human epididymis. This photomicrograph of an H&E–stained section shows the highly coiled ductus epididymis. Its coiled nature is reflected in the variously shaped profiles of the duct. Within the connective tissue are numerous profiles of blood vessels (BV ). The vessels tend to follow the duct; thus they too reflect multiple profiles of several vessels. The section of the duct within the rectangle is shown at higher magnification in Figure 22.23. 30. The ductus deferens is the longest part of the excurrent duct system.


Histology_Ross

Histology_Ross. The ductus deferens (vas deferens) is a direct continuation of the tail of the epididymis (see Fig. 22.1). It ascends along the posterior border of the testis, close to the testicular vessels and nerves. It then enters the abdomen as a component of the spermatic cord, by passing through the inguinal canal. The spermatic cord contains all of the structures that pass to and from the testis. In addition to the ductus deferens, the spermatic cord contains the testicular artery, small arteries to the ductus deferens and cremaster muscle, the pampiniform plexus, lymphatic vessels, sympathetic nerve fibers, and the genital branch of the genitofemoral nerve. All of these structures are surrounded by fascial coverings derived from the anterior abdominal wall. After leaving the spermatic cord, the ductus deferens descends in the pelvis to the level of the bladder, where its distal end enlarges to form the ampulla of ductus deferens. The ampulla is joined there by the duct of the seminal


Histology_Ross

Histology_Ross. FIGURE 22.23 • Photomicrograph of human ductus epididymis. This higher magnification of the rectangular area in Figure 22.22 reveals the two cell types of the epididymal epithelium, the principal cells and the basal cells. Stereocilia (arrows) extend from the apical surface of the principal cells. The nuclei of the basal cells are spherical and are located in close proximity to the basement membrane, whereas the nuclei of the principal cells are cylindrical and conform to the columnar shape of the cell. Surrounding the duct epithelium is a layer of circularly arranged smooth muscle cells. The duct lumen contains numerous sperm. 250. vesicle and continues through the prostate gland to the urethra as the ejaculatory duct.


Histology_Ross

Histology_Ross. vesicle and continues through the prostate gland to the urethra as the ejaculatory duct. The ductus deferens is lined with a pseudostratified columnar epithelium that closely resembles that of the epididymis (Plate 89, page 824). The tall columnar cells also have long microvilli that extend into the lumen. The rounded basal cells rest on the basal lamina. Unlike the epididymis, however, the lumen of the duct does not appear smooth. In histologic preparations (Fig. 22.25), it appears to be thrown into deep longitudinal folds throughout most of its length, probably because of contraction of the thick (1 to 1.5 mm) muscular coat of the duct during fixation.


Histology_Ross

Histology_Ross. The ampulla of ductus deferens has taller, branched mucosal folds that often show glandular diverticula. The muscle coat surrounding the ampulla is thinner than that of the rest of the ductus deferens, and the longitudinal layers disappear near the origin of the ejaculatory duct. The epithelium of the ampulla and ejaculatory duct appears to have a FIGURE 22.24 • Electron micrograph of epididymis. a. Electron micrograph of the epididymal epithelium, showing principal cells (PC) extending to the lumen and a basal cell (BC) limited to the basal portion of the epithelium. Profiles of sperm (S) are seen in the lumen. The apical cytoplasm of the principal cells exhibits numerous long microvilli (stereocilia). 3,000. b. Apical surface of the epithelial cell with its numerous long microvilli (stereocilia). The middle piece of a sperm (S) is evident in the lumen. The small, light circular profiles (arrowheads) are endocytotic vesicles. 13,000.


Histology_Ross

Histology_Ross. secretory function. The cells contain large numbers of yellow pigment granules. The wall of the ejaculatory duct does not have a muscularis layer; the fibromuscular tissue of the prostate substitutes for it. The paired seminal vesicles secrete a fluid rich in fructose.


Histology_Ross

Histology_Ross. The paired seminal vesicles secrete a fluid rich in fructose. The seminal vesicles are paired, elongate, and highly folded tubular glands located on the posterior wall of the urinary bladder, parallel to the ampulla of the ductus deferens. A short excretory duct from each seminal vesicle combines with the ampulla of the ductus deferens to form the ejaculatory duct. Seminal vesicles develop as evaginations of the mesonephric (Wolffian) ducts in the region of future ampullae. The wall of the seminal vesicles contains a mucosa, a thin layer of smooth muscle, and a fibrous coat (Fig. 22.26). The mucosa is thrown into numerous primary, secondary, and tertiary folds that increase the secretory surface area (Plate 91, page 828). All of the irregular chambers thus formed, however, communicate with the lumen.


Histology_Ross

Histology_Ross. The pseudostratified columnar epithelium contains tall, nonciliated columnar cells and short, round cells that rest on the basal lamina. The short cells appear identical to those of the rest of the excurrent duct system. They are the stem cells from which the columnar cells are derived. The columnar cells have the morphology of protein-secreting cells, with a well-developed rER and large secretory vacuoles in the apical cytoplasm.


Histology_Ross

Histology_Ross. The secretion of the seminal vesicles is a whitish yellow, viscous material. It contains fructose, which is the principal metabolic substrate for sperm, along with other simple sugars, amino acids, ascorbic acid, and prostaglandins. Although prostaglandins were first isolated from the prostate gland (hence the name), they are actually synthesized in large amounts in the seminal vesicles. Contraction of the smooth muscle coat of the seminal vesicles during ejaculation discharges their secretion into the ejaculatory ducts and helps to flush sperm out of the urethra. The secretory function and morphology of the seminal vesicles are under the control of testosterone. The prostate, the largest accessory sex gland, is divided into several morphologic and functional zones. The prostate is the largest accessory sex gland of the male reproductive system. Its size and shape are commonly compared to those of a walnut. The main function of the prostate


Histology_Ross

Histology_Ross. FIGURE 22.25 • Photomicrograph of human spermatic cord. a. This low-magnification photomicrograph shows a cross section of the spermatic cord containing several structures. These include the ductus deferens, the accompanying testicular artery and vein, and veins of the pampiniform plexus. 15. Inset. A higher magnification of a pampiniform vein. Note the bundles of longitudinal smooth muscles (cut in cross section) in the tunica adventitia and tunica intima. 55. b. This cross section of the ductus deferens shows the thick muscular wall organized in three distinct smooth muscle layers: an inner longitudinal (SM(L)), middle circular (SM(C)), and outer longitudinal (SM(L)). 100. Inset. A higher magnification shows the pseudostratified epithelium lining the ductus deferens. The tall principal cells possess long microvilli (stereocilia; arrows). The basal cells are in close proximity to the basement membrane and possess spherical nuclei. 215.


Histology_Ross

Histology_Ross. gland is to secrete a clear, slightly alkaline (pH 7.29) fluid that contributes to the formation of seminal fluid. The gland is located in the pelvis, inferior to the bladder, where it surrounds the prostatic part of the urethra. It consists of 30 to 50 tubuloalveolar glands arranged in three concentric layers: an inner mucosal layer, an intermediate submucosal layer, and a peripheral layer containing the main prostatic glands (Fig. 22.27). The glands of the mucosal layer secrete directly into the urethra; the other two layers have ducts that open into the prostatic sinuses located on either side of the urethral crest on the posterior wall of the urethra.


Histology_Ross

Histology_Ross. The adult prostatic parenchyma is divided into four anatomically and clinically distinct zones:  The central zone surrounds ejaculatory ducts as they pierce the prostate gland. It contains about 25% of the glandular tissue and is resistant to both carcinoma and inflammation. In comparison to the other zones, cells in the central zone have distinctive morphologic features (a more prominent and slightly basophilic cytoplasm and a larger nuclei displaced at different levels in adjacent cells). Recent findings suggest that this zone originates embryologically from the inclusion of mesonephric duct cells into the developing prostate.


Histology_Ross

Histology_Ross.  The peripheral zone comprises 70% of the glandular tissue of the prostate. It surrounds the central zone and occupies posterior and lateral parts of the gland. Most prostatic carcinomas arise from the peripheral zone of the prostate gland. The peripheral zone is palpable during digital examination of the rectum. This zone is also the most susceptible to infammation.  The transitional zone surrounds the prostatic urethra; it comprises about 5% of the prostatic glandular tissue and contains the mucosal glands. In older individuals, the parenchymal cells of this zone frequently undergo extensive division (hyperplasia) and form nodular masses of epithelial cells. Because this zone is proximate to the pro-static urethra, these nodules can compress the prostatic urethra, causing diffcult urination. This condition is known as benign prostatic hyperplasia (BPH) and is discussed in Folder 22.4 (page 811).


Histology_Ross

Histology_Ross. FIGURE 22.26 • Photomicrograph of human seminal vesicle a. This low-magnification photomicrograph shows part of an H&E–stained section of a human seminal vesicle. This gland is a tortuous tubular structure and in a section exhibits what appear to be a number of isolated lumina. In actuality, there is only one lumen. The mucosa is characterized by extensive folding (arrows). It rests on a thick smooth muscle (SM) investment that is organized in two layers: an inner circular layer and an outer longitudinal layer. 20. b. This higher magnification shows the mucosal folds surfaced by a pseudostratified epithelium. Arrows indicate the basal cells. 500. FIGURE 22.27 • Schematic drawing of the zones of the human prostate gland. This drawing illustrates the relative location, by color, of the four zones of the prostate gland and anterior fibromuscular stroma of the gland.


Histology_Ross

Histology_Ross.  The periurethral zone contains mucosal and submucosal glands. In later stages of BPH, this zone may undergo pathologic growth but mainly from the stromal components. Together with the glandular nodules of the transitional zone, this growth causes increased urethral compression and further retention of urine in the bladder. In addition, fbromuscular stroma occupies the anterior surface of the prostate gland anterior to the urethra and is composed of dense irregular connective tissue with large amount of smooth muscle fibers. The growth of the prostatic glandular epithelium is regulated by the hormone dihydrotestosterone.


Histology_Ross

Histology_Ross. Within each prostate zone, the glandular epithelium is generally simple columnar, but there may be patches that are simple cuboidal, squamous, or occasionally pseudostratified (Fig. 22.28). The alveoli of the prostatic glands, especially those in older men, often contain prostatic concretions (corpora amylacea) of varied shape and size, often up to 2 mm in diameter (see Fig. 22.28 and Plate 90, page 826). They appear in sections as concentric lamellated bodies  FOLDER 22.4 Clinical Correlation: Benign Prostatic Hypertrophy and Cancer of the Prostate chapter 22 Male Reproductive System PROSTATE G LAN D 811 Benign prostatic hypertrophy (nodular hyperplasia, BPH) occurs almost exclusively in the transitional and peri-urethral zones, leading to partial or total obstruction of the urethra (Fig. F22.4.1a). A widely accepted theory of the pathogenesis of BPH is related to the action of dihy-drotestosterone (DHT). DHT is synthesized in the stromal cells by conversion from circulating


Histology_Ross

Histology_Ross. (Fig. F22.4.1a). A widely accepted theory of the pathogenesis of BPH is related to the action of dihy-drotestosterone (DHT). DHT is synthesized in the stromal cells by conversion from circulating testosterone in the presence of 5-reductase. Once synthesized, DHT acts as an autocrine agent on the stromal cells and as a paracrine hormone on the glandular epithelial cells, causing them to proliferate (Fig. F22.4.1b). BHP is believed to occur to some extent in all men by age 80. Several options are available to treat BHP. Noninva-sive treatment includes medications (–receptor block-ers) to relax the prostate smooth muscles and relieve pressure on the compressed urethra. Clinical trials have shown that inhibitors of 5-reductase reduce the DHT concentration and thus decrease the size of the prostate and reduce urethral obstruction. Minimally invasive treatment options use laser, microwave, or radiofrequency energy to destroy the prostate tissue causing urethral obstruction. These include


Histology_Ross

Histology_Ross. and reduce urethral obstruction. Minimally invasive treatment options use laser, microwave, or radiofrequency energy to destroy the prostate tissue causing urethral obstruction. These include interstitial laser coagulation (ILC), microwave hyperthermia, and transurethral needle ablation (TUNA). Finally, a variety of surgical procedures are used to remove hypertrophied regions of the prostate gland. They include transurethral in-cision of the prostate (TUIP), a more extensive transurethral resection of the prostate (TURP), and most recently, a mod-ification of the TURP procedure that uses laser energy to vaporize the prostate tissue called Greenlight PVP. Cancer of the prostate is one of the most common cancers in the male: the lifetime risk of developing prostate cancer is 16.7% (1 in 6). The incidence of prostatic cancer increases with age, and it is estimated that 70% of men be-tween the ages of 70 and 80 will develop this disease. Tumors usually develop in the peripheral zone of


Histology_Ross

Histology_Ross. The incidence of prostatic cancer increases with age, and it is estimated that 70% of men be-tween the ages of 70 and 80 will develop this disease. Tumors usually develop in the peripheral zone of the gland. In the past, early detection was uncommon, because the ab-normal growth of the tumor did not impinge on the urethra to produce symptoms that demanded prompt attention. There-fore, prostatic cancer was often inoperable by the time it was discovered. However, beginning in the late 1980s, the introduction of prostate-specific antigen (PSA) testing for aabba b FIGURE F22.4.1 • Benign prostatic hyperplasia (BPH) a. This photograph shows a horizontal section through the prostate gland from an individual with BPH. The cut section shows numerous well-defined nodules that compress prostatic urethra (marked with paper clip). b. Photomicrograph of prostatic glands shows the hypertrophy of epithelium lining the glands. Note that the cells form folds that protrude into the lumen of the glands.


Histology_Ross

Histology_Ross. (marked with paper clip). b. Photomicrograph of prostatic glands shows the hypertrophy of epithelium lining the glands. Note that the cells form folds that protrude into the lumen of the glands. 200. (Reprinted with permission from Rubin E, Gorstein F, Schwarting R, Strayer DS. Rubin’s Pathology, 4th ed. Baltimore: Lippincott Williams & Wilkins, 2004; Fig. 17–40.) continued next page and are believed to be formed by precipitation of secretory material around cell fragments. They may become partially calcified.


Histology_Ross

Histology_Ross. The glandular epithelium is influenced by sex hormones, such as testosterone and adrenal androgens. These hormones enter the secretory cells of glandular epithelium and are converted to dihydrotestosterone (DHT) by the enzyme 5-reductase. DHT is approximately 30 times more potent than testosterone. The binding of DHT to the androgen receptor (AR) results in a conformational change of the receptor and its relocation from the cytosol to the cell nucleus. Here the phosphorylated dimers of AR complex bind to a specific sequence of DNA known as a hormone-response element residing in the promoter regions of target genes. The primary function for AR is direct upor down-regulation of specific gene transcription. DHT stimulates growth of normal prostatic epithelium and proliferation and growth of BPH and androgen-dependent prostate cancer. The prostate gland secretes prostatic acid phosphatase (PAP), fibrinolysin, citric acid, and prostate-specific antigen (PSA).


Histology_Ross

Histology_Ross. The prostate gland secretes prostatic acid phosphatase (PAP), fibrinolysin, citric acid, and prostate-specific antigen (PSA). The epithelial cells in prostate gland produce several enzymes, particularly prostate-specific antigen (PSA), pro-static acid phosphatase (PAP), fibrinolysin, and citric acid.


Histology_Ross

Histology_Ross.  Prostate-specifc antigen (PSA), a 33-kilodalton serine protease, is one of the most clinically important tumor markers. In normal conditions, PSA is secreted into prostatic gland alveoli and ultimately incorporated into seminal fluid. The alveolar secretion from the prostate gland is pumped into the prostatic urethra during ejaculation by contraction of the fibromuscular tissue of the prostate. Because PSA is predominately released into prostatic secretion, only a very small amount of PSA (usually below 4 ng/mL) is circulating in the blood of a healthy individual. However, in prostate cancer, serum concentration of PSA increases; large amounts of PSA are produced and misdirected into the circulation by the transformed prostatic epithelium. Therefore, the elevated levels of PSA are directly related to increased activity of the prostatic cancer cells. A PSA level between 4 and 10 ng/mL suggests about 25% percent cancer risk; levels above 10 ng/mL suggest a risk greater than 67%. An


Histology_Ross

Histology_Ross. related to increased activity of the prostatic cancer cells. A PSA level between 4 and 10 ng/mL suggests about 25% percent cancer risk; levels above 10 ng/mL suggest a risk greater than 67%. An increased PSA serum level is used as marker for the presence and progression of the disease. Recently, it has become widely accepted that small amounts of PSA are also present in many nonprostatic tissues, including breast, ovary, salivary gland, and liver tissue, and in various tumors. It is also important to mention that high circulating levels of PSA can be associated with benign (noncancerous) conditions such as prostatitis (infection of the prostate gland), interrupted blood fow to the prostate, or BPH.


Histology_Ross

Histology_Ross.  The prostatic acid phosphatase (PAP) (100-kilodalton) enzyme regulates cell growth and metabolism of prostate glandular epithelium. Because elevated serum levels of PAP are found in patients with metastatic prostate cancer, this enzyme is routinely used as an alternate marker to PSA for prostatic tumors. Measurements of PAP and PSA are useful in assessing the prognosis of prostate cancer.  Fibrinolysin, secreted from the prostate gland, liquefies semen. The bulbourethral glands secrete preseminal fluid. The paired bulbourethral glands (Cowper’s glands) are pea-sized structures located in the urogenital diaphragm (see Fig. 22.1). The duct of each gland passes through the inferior fascia of the urogenital diaphragm and joins the initial portion of the penile urethra. The glands are compound tubuloalveolar glands that structurally resemble mucus secretory glands (Fig. 22.29). The simple columnar epithelium, which varies considerably in height depending


Histology_Ross

Histology_Ross. FIGURE 22.28 • Photomicrograph of human prostate gland. a. This Mallory-azan–stained specimen shows the tubuloalveolar glands (Gl) and the fibromuscular tissue that forms the septa between glandular tissue. Within the lumina, various-sized prostatic concretions can be seen. The stain used for this specimen readily distinguishes the smooth muscle component (stained red) from the dense connective tissue component (stained blue) of the stroma. 60. b. This higher magnification shows an area where the glandular epithelium is pseudostratified. The round nuclei adjacent to the connective tissue (arrowheads) belong to the basal cells. Those nuclei that are more elongate and further removed from the base of the epithelium belong to the secretory cells. Note the terminal bars (arrows) that are evident at the apical region of these cells. The red-stained sites within the dense connective tissue represent smooth muscle cells. 635.


Histology_Ross

Histology_Ross. on the functional state of the gland, is under the control of testosterone. The clear, mucus-like glandular secretion contains considerable amounts of galactose and galactosamine, galacturonic acid, sialic acid, and methylpentose. Sexual stimulation causes release of this secretion, which constitutes the major portion of the preseminal fuid and probably serves to lubricate the penile urethra. Semen contains fluids and sperm from the testis and secretory products from the epididymis, ductus deferens, prostate, seminal vesicles, and bulbourethral glands. It is alkaline and may help to neutralize the acid environment of the urethra and the vagina. Semen also contains prostaglandins that may influence sperm transit in both the male and female reproductive ducts and that may have a role in implantation of a fertilized ovum.


Histology_Ross

Histology_Ross. The average ejaculate of semen has a volume of about 3 mL and normally contains up to 100 million sperm per milliliter. It is estimated that 20% of the sperm in any ejaculate are morphologically abnormal and nearly 25% are immotile. Erection of the penis involves the filling of the vascular spaces of the corpora cavernosa and corpus spongiosum. The penis consists principally of two dorsal masses of erectile tissue, the corpora cavernosa, and a ventral mass of erectile


Histology_Ross

Histology_Ross. The penis consists principally of two dorsal masses of erectile tissue, the corpora cavernosa, and a ventral mass of erectile FIGURE 22.29 • Photomicrograph of human bulbourethral gland. This photomicrograph shows an H&E–stained section of the compound tubuloalveolar bulbourethral gland. The epithelium consists of columnar mucus-secreting cells. The nuclei are displaced to the base of the cells by the accumulated secretory material that they contain. The cytoplasm has an appearance similar to typical mucus-secreting cells. Note several ducts (D) lined by a simple columnar epithelium. The ducts will merge to form a single excretory duct. In some sites the ducts contain mucus-secreting cells (arrows). 40.


Histology_Ross

Histology_Ross. tissue, the corpus spongiosum, in which the spongy part of the urethra is embedded. A dense, fibroelastic layer, the tunica albuginea, binds the three together and forms a capsule around each (Fig. 22.30). The corpora cavernosa contain numerous wide, irregularly shaped vascular spaces lined with vascular endothelium. These spaces are surrounded by a thin layer of smooth muscle that forms trabeculae within the tunica albuginea interconnecting and criss-crossing the corpus cavernosum. Irregular smooth muscle bundles are observed frequently as “subendothelial cushions” surrounding irregular vascular spaces (Fig. 22.31). The interstitial connective tissue contains many nerve endings and lymphatic vessels. The vascular spaces increase in size and rigidity by filling with


Histology_Ross

Histology_Ross. FIGURE 22.30 • Photomicrograph of a histologic section of the penis. This photomicrograph shows an H&E–stained specimen of a cross section of the penis near the base of the organ. Note the arrangement of the corpora cavernosa and corpus spongiosum; the latter contains the urethra. 3. blood, principally derived from the helicine arteries. These arteries dilate during erection (see Folder 22.5) to increase the blood flow to the penis. An arteriovenous (AV) anastomosis exists between the deep artery of the penis and the peripheral venous system (Folder 22.5).


Histology_Ross

Histology_Ross. The skin of the penis is thin and loosely attached to the underlying loose connective tissue except at the glans penis, where it is very thin and tightly attached. The skin of the glans is so thin that blood within its large, muscular anastomosing veins that drain the corpus spongiosum may give it a bluish color. There is no adipose tissue in the subcutaneous tissue. There is, however, a thin layer of smooth muscle that is continuous with the dartos layer of the scrotum. In uncircumcised males, the glans is covered with a fold of skin, the prepuce, which resembles a mucous membrane on its inner aspect. Numerous sebaceous glands are present in the skin of the penis just proximal to the glans.


Histology_Ross

Histology_Ross. The penis is innervated by somatic, sympathetic, and parasympathetic nerves. Many sensory nerve endings are distributed throughout the tissue of the penis, and sympathetic and parasympathetic visceral motor fibers innervate the smooth muscle of the trabeculae of the tunica albuginea and the blood vessels. Both sensory and visceral motor fibers play essential roles in erectile and ejaculatory responses.


Histology_Ross

Histology_Ross. CNS and maintained by complex interactions between vascular and neurologic events. The CNS responds to external or internal stimuli (sensory impulses, perception, desire, etc.) that involve the sympathetic and parasympa-thetic innervation of the penis. Parasympathetic stimulation initiates erection by relaxation of the trabecular smooth muscle cells and dila-tion of the helicine arteries. This leads to expansion of the corpora cavernosa and, to a lesser degree, the corpus spongiosum. Arterial blood accumulates in these erectile tissues by compression of the venules against the nondis-tensible tunica albuginea. This process is referred to as the corporal venoocclusive mechanism. The tunica albuginea also compresses the larger veins that drain blood from the corpora cavernosa so that venous outflow is also blocked, resulting in tumescence, and rigidity of the penis. Two neuromediators, acetylcholine and nitric oxide, are involved in the relaxation of smooth muscle during the initi-ation


Histology_Ross

Histology_Ross. outflow is also blocked, resulting in tumescence, and rigidity of the penis. Two neuromediators, acetylcholine and nitric oxide, are involved in the relaxation of smooth muscle during the initi-ation and maintenance of penile erection. nerve endings and acts primarily on the endothelial cells that line the vascular spaces of the corpora cavernosa. This causes the release of vasoactive intestinal peptide (VIP) and, more importantly, nitric oxide.  Nitric oxide (NO) activates guanylate cyclase in the trabecular smooth muscle cells to produce cyclic guanosine monophosphate (cGMP). cGMP causes the smooth muscle cells to relax. Sympathetic stimulation terminates penile erection by causing contraction of the trabecular smooth muscle cells of the helicine arteries. These events decrease the flow of blood to the corpora cavernosa, reducing blood pressure in the erectile tissue to normal venous pressure. The lower pressure within the corpus cavernosum allows the veins leading from the corpora


Histology_Ross

Histology_Ross. of blood to the corpora cavernosa, reducing blood pressure in the erectile tissue to normal venous pressure. The lower pressure within the corpus cavernosum allows the veins leading from the corpora cavernosa to open and drain the excess blood. Erectile dysfunction (ED) is an inability to achieve and maintain sufficient penile erection to complete satisfactory intercourse. Adequate arterial blood supply is critical for continued next page


Histology_Ross

Histology_Ross. FIGURE 22.31 • Photomicrograph of corpus spongiosum. a. This photomicrograph of an H&E–stained section shows the corpus spongiosum and urethra. 20. b. This higher magnification of the corpus spongiosum shows the numerous irregularly shaped vascular spaces. Note the surrounding layer of smooth muscle (SM) forming the “subendothelial cushions.” 135.  FOLDER 22.5 Clinical Correlation: Mechanism of Erection and Erectile Dysfunction Erection of the penis is a vascular event initiated by the  Acetylcholine is released by the parasympathetic This page intentionally left blank.


Histology_Ross

Histology_Ross. This page intentionally left blank. The male reproductive system consists of the paired testes, epididymides, and genital ducts, as well as accessory reproductive glands and the penis. The functions of the testis are the production of sperm and the synthesis and secretion of androgens, especially testosterone. The events of cell division that lead to the mature sperm involve both normal cell division, mitosis, and reduction division, meiosis, to yield a hap-loid chromosome number and haploid DNA content. Androgen secretion by the testis begins early in fetal development and is essential for continued normal development of the male fetus. At puberty, androgen secretion resumes and is responsible for initiation and maintenance of sperm production (spermatogenesis), secretion by accessory sex glands (e.g., prostate and seminal vesicles), and development of secondary sex characteristics. Testis, monkey, H&E 65.


Histology_Ross

Histology_Ross. Testis, monkey, H&E 65. This section of the testis shows the seminiferous tubules and the tunica albuginea (TA), the capsule of the organ. Extending from the very thick capsule are connective tissue septa (S) that divide the organ into compartments. Each compartment contains several seminiferous tubules and represents a lobule (L). Blood vessels (BV) are present within the inner portion of the capsule, the part referred to as the tunica vasculosa, and in the connective tissue septa. The seminiferous tubules are convoluted; thus, the profiles they present in a section are variable in appearance. Not infrequently, the wall of a tubule is sectioned tangentially, thus obscuring the lumen and revealing what appears to be a solid mass of cells (X). Seminiferous tubules, testis, monkey, H&E 400.


Histology_Ross

Histology_Ross. Seminiferous tubules, testis, monkey, H&E 400. Examination at higher magnification, as in this figure, reveals a population of interstitial cells that occur in small clusters and lie in the space between adjoining tubules. They consist mostly of Leydig cells (LC), the chief source of testosterone in the male. They are readily identified by virtue of their location and by their small round nucleus and eosinophilic cytoplasm. Macrophages are also found, in close association with the Leydig cells, but in lesser number. They are, however, difficult to identify in H&E sections.


Histology_Ross

Histology_Ross. A layer of closely apposed squamous cells forms a sheath-like investment around the tubule epithelium of each seminiferous tubule. In man, several layers of cells invest the tubule epithelium. The cells of this peritubular investment exhibit myoid features and account for the slow peristaltic activity of the tubules. Peripheral to the myoid layer is a broad lymphatic channel that occupies an extensive space between the tubules. In routine histologic sections, however, the lymphatic channels are usually collapsed and, thus, unrecognizable. The cellular elements that surround the tubule epithelium are generally referred to as a lamina propria (LP) or as a boundary tissue. As a lamina propria, it is atypical. It is not a loose connective tissue. Indeed, under normal circumstances, lymphocytes and other cell types related to the immune system are conspicuously absent.


Histology_Ross

Histology_Ross. Examination of the tubule epithelium reveals two kinds of cells: a proliferating population of spermatogenic cells and a nonproliferating population, the sustentacular, or Sertoli, cells. The Sertoli cells are considerably fewer and can be recognized by their elongate, pale-staining nuclei (Sn) and conspicuous nucleolus. The Sertoli cell cytoplasm extends from the periphery of the tubule to the lumen.


Histology_Ross

Histology_Ross. The spermatogenic cells consist of successive generations arranged in concentric layers. Thus, the spermatogonia (Sg ) are found at the periphery. The spermatocytes (Sc), most of which have large round nuclei with a distinctive chromatin pattern (because of their chromatin material being reorganized), come to lie above the spermatogonia. The spermatid population (Sp) consists of one or two generations and occupies the site closest to the lumen. The tubules in this figure have been identified according to their stage of development. The tubule at the upper right can be identified as stage VI. At this stage, the mature population of spermatids (identified by their dark-blue heads and eosinophilic threadlike flagella protruding into the lumen) are in the process of being released (spermiogenesis). The younger generation of spermatids is composed of round cells and exhibits round nuclei. Moving clockwise, the tubule indicated as stage VII is slightly more advanced. The mature spermatids


Histology_Ross

Histology_Ross. The younger generation of spermatids is composed of round cells and exhibits round nuclei. Moving clockwise, the tubule indicated as stage VII is slightly more advanced. The mature spermatids are now gone. Progressing to stage VIII, the tubule at the bottom of the micrograph reveals that the spermatid population is undergoing a change in nuclear shape. Note the tapered nuclei (arrows). Further maturation of the spermatids is reflected in the tubule at the top of the micrograph, stage XI. Finally, the tubule marked stage II, on the left, reveals slightly greater maturation of the luminal spermatids, and with the start of the new cycle (stage I), a newly formed spermatid population is now present. By examining the spermatid population and assessing the number of generations present (i.e., one or two) and the degree of maturation, it is possible with the aid of a chart to approximate the stage of a tubule.


Histology_Ross

Histology_Ross. KEY BV, blood vessels L, lobule LC, Leydig cells LP, lamina propria S, connective tissue septa Sc, spermatocytes Sg, spermatogonia Sn, Sertoli nuclei Sp, spermatids TA, tunica albuginea X, tangential section of tubule with lumen obscured arrows, spermatid nuclei displaying early shape change


Histology_Ross

Histology_Ross. While the mature testis is characterized by seminiferous tubules, the immature testis is characterized by cords of cells consisting of an epithelium of sustentacular (Sertoli) cells surrounding occasional gonocytes, precursors of spermatogonia that are derived from the primordial germ cells that invaded the developing gonad in the embryo. At puberty, these cords become canalized, and the gonocytes begin the multiple divisions that give rise to the spermatogonia that, in turn, will divide and differentiate into the mature sperm. The seminiferous tubules terminate as straight tubules (tubuli recti) that are lined only by Sertoli cells. The tubuli recti lead to the rete testis, a complex series of anastomosing channels in the mediastinum testis that is the termination of the intratesticular tubule system. Prepubertal testis, newborn human, H&E 180; inset 360.


Histology_Ross

Histology_Ross. Prepubertal testis, newborn human, H&E 180; inset 360. The various germ cell types representative of spermatogenesis in the mature seminiferous tubules are not present in the testis before puberty or in the postpubertal undescended testis. Instead, the “tubules” are represented by cords of cells in which a lumen is lacking. The seminiferous cords display the same tortuosity as in the adult; the tunica albuginea (TA) of the testis, though thinner, is of the same relative thickness.


Histology_Ross

Histology_Ross. The seminiferous cords are of considerably smaller diameter than the tubules of the adult and are composed of two cell types: the gonocyte, or first-generation spermatogonium, derived from the primordial germ cell that migrates from the yolk sac to the developing gonad in the embryo; and a cell that resembles the Sertoli cell of the adult. The latter cell type predominates and constitutes the bulk of the cord. The cells are columnar, and their nuclei are close to the basement membrane. The gonocytes (G) are the precursors of the definitive germ cells, or spermatogonia. They are round cells Mediastinum testis, testis, monkey, H&E 65.


Histology_Ross

Histology_Ross. Mediastinum testis, testis, monkey, H&E 65. In the posterior portion of the testis, the connective tissue of the tunica albuginea extends more deeply into the organ. This inward extension of connective tissue is called the mediastinum testis. It contains a network of anastomosing channels called the rete testis. Only a small portion of the mediastinum testis (MT) is evident in the figure. The area includes, however, a few seminiferous tubules (ST) in the upper portion of the micrograph Straight tubule, testis, monkey, H&E 400.


Histology_Ross

Histology_Ross. Straight tubule, testis, monkey, H&E 400. The straight tubule or tubulus rectus (TR) in this figure appears to end on one side before it ends on the other. This simply reflects the angle of section. When the straight tubule ends, however, the epithelial lining suddenly becomes cuboidal. This represents the rete testis, which constitutes an anastomosing system of channels that lead to the efferent ductules. The that have a centrally placed, spherical nucleus. The cytoplasm takes little stain and usually appears as a light ring around the nucleus. This gives the gonocyte a distinctive appearance in histologic sections (inset). Generally, the gonocytes are found at the periphery of the cord, but many are also found more centrally. The gonocytes give rise to spermatogonia that begin to proliferate in males between the ages of 10 and 13 years. The seminiferous epithelium then becomes populated with cells at various stages of spermatogenesis, as seen in the adult.


Histology_Ross

Histology_Ross. The seminiferous cords are surrounded by one or two layers of cells with long processes and flat nuclei. They resemble fibroblasts at the ultrastructural level and give rise to the myoid peritubular cells of the adult. The interstitial cells (of Leydig) are conspicuous in the newborn, a reflection of the residual effects of maternal hormones. Leydig cells, however, regress and do not become conspicuous again until puberty. In this preparation, the Leydig cells (LC) can be seen between the cords (inset). They are ovoid or polygonal and are closely grouped, so that adjacent cells are in contact with each other. Overall, they have the same appearance as the Leydig cells of the adult.


Histology_Ross

Histology_Ross. and, fortuitously, the site where one of the seminiferous tubules terminates and joins the rete testis (RT). This can be recognized in the area delineated by the rectangle, which is shown at higher magnification in figure below. As noted above, the seminiferous tubules are arranged in the form of a loop, with each end joining the rete testis. The seminiferous tubules open into the rete testis by way of a straight tubule. Straight tubules are very short and are lined by Sertoli-like cells; no germ cell component is present. epithelial lining cells of the rete are sometimes more squamous than cuboidal or, occasionally, may be low columnar in appearance. Typically, they possess a single cilium; however, this is difficult to see in routine H&E preparations.


Histology_Ross

Histology_Ross. The connective tissue of the mediastinum is very dense but exhibits no other special features, nor is smooth muscle present. Adipose cells (AC) and blood vessels (BV), particularly veins of varying size, are present within the connective tissue. KEY AC, adipose cells BV, blood vessels G, gonocytes LC, Leydig cells MT, mediastinum testis RT, rete testis ST, seminiferous tubules TA, tunica albuginea TR, tubulus rectus


Histology_Ross

Histology_Ross. The rete testis, in turn, is connected via 20 efferent ductules (ductuli efferentes; remnants of nephrons of the fetal mesonephric kidney) to the ductus epididymis. These are the first elements of the excurrent duct system of the male genital system. Most of the fluid secreted in the seminiferous tubules is reabsorbed in the efferent ductules. The muscular coat characteristic of the excurrent duct system first appears at the beginning of the efferent ductules. The ductus epididymis is a highly coiled tube, 4 to 6 m long; sperm mature during their passage along its length, acquiring motility as well as the ability to fertilize an egg. This maturation is also androgen dependent and involves changes in the sperm plasma membrane and addition to the glycocalyx of glycoproteins secreted by the epididymal epithelial cells. Efferent ductules, testis-epididymis, monkey, H&E 60; inset 360.


Histology_Ross

Histology_Ross. About 12 to 20 efferent ductules leave the testis and serve as channels from the rete testis to the ductus epididymis. Each of the efferent ductules undergoes numerous spiral windings and convolutions to form a group of conical structures; together they constitute the initial part of the head of the epididymis. When examined in a 822 tissue section, the ductules exhibit a variety of irregular profiles due to their twisting and turning. This is evident on the right side of this micrograph. The epithelium that lines the efferent ductules is distinctive in that groups of tall columnar cells alternate with groups of cuboidal cells, giving the luminal surface an unevenly contoured appearance. Thus, small cup-like depressions are created where the epithelium contains groups of cuboidal or low columnar cells. Typically, these shorter cells exhibit a brush border-like apical surface because of the microvilli that they possess (arrowhead, inset).


Histology_Ross

Histology_Ross. PLATE 88 • E FFE R E NT DUCTU LE S AN D E P I DI DYM I S KEY AT, adipose tissue BV, blood vessel C, cilia CT, connective tissue P, pigment SC, stereocilia SM, smooth muscle arrowhead (inset), brush border arrows, “islands” of epithelium in the lumen Epididymis, monkey, H&E 180. The epididymis, by virtue of its shape, is divided into a head, body, and tail. The initial part of the head contains the ductus epididymis, a single convoluted duct into which the efferent ductules open. The duct is, at first, highly convoluted but becomes less tortuous in the body and tail. A section through the head of the epididymis, as shown in figure above, cuts the ductus epididymis in numerous places, and as in the efferent ductules, different-shaped profiles are observed.


Histology_Ross

Histology_Ross. The epithelium contains two distinguishable cell types: tall columnar cells and basal cells similar to those of the efferent ductules. The epithelium is, thus, also pseudostratified columnar. The columnar cells are tallest in the head of the epididymis and diminish in height as the tail is reached. The free surface of the cell possesses stereocilia (SC). These are extremely long, branching microvilli. They evidently adhere to each other during the preparation of the tissue to form the fine tapering structures that are characteristically seen with the light microscope. The nuclei of the columnar cells are elongated and are located a moderate distance from the base of the cell.


Histology_Ross

Histology_Ross. The basal surface of the ductule, in contrast, has a smooth contour (see figure below and inset). Some of the cells, generally the tall columnar cells, possess cilia (C) (inset). Whereas the ciliated cells aid in moving the contents of the tubule toward the epididymis, the cells with the microvilli are largely responsible for absorbing fluid from the lumen. In addition to the columnar and cuboidal cells, basal cells are also present; thus, the epithelium is designated pseudostratified columnar. The basal cells possess little cytoplasm and presumably serve as stem cells.


Histology_Ross

Histology_Ross. The efferent ductules possess a thin layer of circularly arranged smooth muscle cells (SM, inset). The muscle is close to the basal surface of the epithelial cells, being separated from it by only a small amount of connective tissue (CT, inset). Because of this close association, the smooth muscle may be overlooked or misidentified as connective tissue. Smooth muscle facilitates movement of luminal contents of the ductule to the ductus epididymis. They are readily distinguished from the spherical nuclei of the basal cells that lie close to the basement membrane. Other conspicuous features of the columnar cells include a very large supranuclear Golgi apparatus (not seen at the magnification offered here), pigment accumulations (P), and numerous lysosomes, demonstrable with appropriate techniques.


Histology_Ross

Histology_Ross. Because of the unusual height of the columnar cells and, again, the tortuosity of the duct, an uneven lumen appears in some sites; indeed, even “islands” of epithelium can be encountered in the lumen (see arrows, figure above). Such profiles are accounted for by sharp turns in the duct where the epithelial wall on one side of the duct is partially cut. For example, a cut in the plane of the double-headed arrow indicated in this figure would create such an isolated epithelial island. A thin layer of smooth muscle circumscribes the duct and appears similar to that associated with the efferent ductules. In the terminal portion of the epididymis, however, the smooth muscle acquires a greater thickness, and longitudinal fibers are also present. Beyond the smooth muscle coat there is a small amount of connective tissue (CT) that binds the loops of the duct together and carries the blood vessels (BV) and nerves.


Histology_Ross

Histology_Ross. The ductus (vas) deferens continues from the duct of the epididymis as a thick-walled muscular tube that leaves the scrotum and passes through the inguinal canal as a component of the spermatic cord. At the deep inguinal ring, it continues into the pelvis and, behind the urinary bladder, joins with the excretory duct from the seminal vesicle to form the ejaculatory duct. The ejaculatory duct then pierces the prostate gland and opens into the urethra. Mature sperm are stored in the terminal portion (tail) of the ductus epididymis. These sperm are forced into the ductus deferens by intense contractions of the three smooth muscle layers of the ductus deferens following appropriate neural stimulation. Contraction of the smooth muscle of the ductus deferens continues the movement of the sperm through the ejaculatory duct into the urethra during the ejaculatory reflex. The seminal vesicles (see Plate 91) are not storage sites for sperm but, rather, secrete a fructose-rich fluid that becomes


Histology_Ross

Histology_Ross. the ejaculatory duct into the urethra during the ejaculatory reflex. The seminal vesicles (see Plate 91) are not storage sites for sperm but, rather, secrete a fructose-rich fluid that becomes part of the ejaculated semen. Fructose is the principal metabolic substrate for sperm.


Histology_Ross

Histology_Ross. Spermatic cord, human, H&E 80. A cross section through the ductus deferens and some of the vessels and nerves that accompany the duct in the spermatic cord are shown in this figure. The wall of the ductus deferens is extremely thick, mostly because of the presence of a large amount of smooth muscle. The muscle contracts when the tissue is removed, causing the mucosa to form longitudinal folds. For this reason, in histologic sections, the lumen (L) usually appears irregular in cross section.


Histology_Ross

Histology_Ross. The smooth muscle of the ductus deferens is arranged as a thick outer longitudinal layer (SM(L)), a thick middle circular layer (SM(C)), and a thinner inner longitudinal layer (SM(L)). Between the epithelium and the inner longitudinal smooth muscle layer there is a moderately thick cellular layer of loose connective tissue, the lamina propria (LP). The connective tissue immediately surrounding the ductus deferens contains nerves and some of the smaller blood vessels that supply the duct. In fact, some of these vessels can be seen penetrating the outer longitudinal smooth muscle layer (asterisks). SPERMATIC CORD AND DUCTUS DEFERENS KEY BV, blood vessels CT, connective tissue L, lumen of ductus deferens LP, lamina propria Lu, lumen of blood vessel N, nerve SM(C), circular layer of smooth muscle SM(L), longitudinal layer of smooth muscle arrowheads, stereocilia arrows, basal cell nucleus asterisks, small arteries supplying ductus deferens Ductus deferens, human, H&E 320; inset 250.


Histology_Ross

Histology_Ross. Ductus deferens, human, H&E 320; inset 250. The epithelial lining of the ductus deferens consists of pseudostratified columnar epithelium with stereocilia (arrowheads). It resembles the epithelium of the epididymis, but the cells are not as tall. The elongated nuclei of the columnar cells are read ily distinguished from the spherical nuclei of the basal cells (arrows). The epithelium rests on a loose connective tissue that extends to the smooth muscle; no submucosa is described. A unique feature of the spermatic cord is the presence of a plexus of atypical veins (pampiniform plexus) that arise from the spermatic veins.


Histology_Ross

Histology_Ross. A unique feature of the spermatic cord is the presence of a plexus of atypical veins (pampiniform plexus) that arise from the spermatic veins. These vessels receive the blood from the testis. (The pampiniform plexus also receives tributaries from the epididymis.) The plexus is an anastomosing vascular network that constitutes the bulk of the spermatic cord. Portions of several of these veins (BV) are evident in the upper right of figure above along with a number of nerves (N). The unusual feature of the veins is their thick muscular wall that, at a glance, gives the appearance of an artery rather than a vein. Careful examination of these vessels (inset) shows that the bulk of the vessel wall is composed of two layers of smooth muscle—an outer circular layer SM(C) and an inner longitudinal layer SM(L).


Histology_Ross

Histology_Ross. The prostate gland is the largest accessory sex gland. It consists of 30 to 50 tubuloalveolar glands that surround the proximal urethra. Because of this relationship, a common condition in later life, benign prostatic hyperplasia, can result in partial or total obstruction of the urethra. The prostatic glands are arranged in three concentric layers: a mucosal layer, a submucosal layer, and a peripheral layer containing the main prostatic glands. The mucosal glands secrete directly into the urethra; the other two sets of glands deliver their secretions through ducts that open into the prostatic sinuses on the posterior wall of the urethra. All of the glands are made up of a pseudostratified columnar epithe-lium that secretes several components of the semen, including acid phosphatase, citric acid (a nutrient for sperm), and fibrinolysin (which keeps the semen liquified). Aggregations of dead epithelial cells and precipitated secretory products form prostatic concretions in the alveoli


Histology_Ross

Histology_Ross. acid (a nutrient for sperm), and fibrinolysin (which keeps the semen liquified). Aggregations of dead epithelial cells and precipitated secretory products form prostatic concretions in the alveoli of the glands; these are a characteristic feature that aids in recognition of the prostate. The stroma is characterized by numerous small bundles of smooth muscle, so that it can also be described as a fbromuscular stroma. Contraction of this muscle occurs at ejaculation, forcing the secretion into the urethra. Surrounding the gland is a fibroelastic capsule that also contains small bundles of smooth muscle.


Histology_Ross

Histology_Ross. Prostate gland, human H&E 47. A portion of the prostate gland in shown in this low-magnification micrograph. A small section of the capsule (Cap) of the gland is seen in the upper left corner. The rest of the field is filled with the glandular and stromal components of the prostate. The secretory tubuloalveoli of the prostate gland vary greatly in form, as is evident in the figure. They may appear as tubes, as isolated alveoli, as alveoli with branches, or as tubes with branches. Tangential sections through alveoli may even produce the appearance of “epithelial islands” (arrowheads) in the lumen of the alveoli.


Histology_Ross

Histology_Ross. This is due to the extremely uneven contour of the epithelial surface. It should also be noted that many of the alveoli may appear rudimentary in structure (arrows). These are simply in an inactive state and are increasingly observed in older individuals. As noted above, aggregations of dead epithelial cells and precipitated secretions form prostatic concretions (C) in the lumina of the alveoli; these gradually increase in number and size with age. The concretions stain with eosin and may have a concentric lamellar appearance, as is clearly shown in the concretion in the lower right. With time, they may become impregnated with calcium salts and thus be easily recognized in X-rays of the lower abdomen. Glands and fbromuscular stroma, prostate, human, H&E 178; upper inset 350; lower inset 650.


Histology_Ross

Histology_Ross. In this higher magnification view of a portion of the prostate gland, the fbromuscular stroma is clearly seen both immediately subtending the secretory epithelium of the tubuloalveoli as well as in deeper, nonsecretory areas. In the upper inset, corresponding to the larger rectangle, the intensity of the staining of the smooth muscle (SM) clearly distinguishes it from the fibrous stromal connective tissue with which it is intimately intermingled. There are no clearly outlined bundles or layers of smooth muscle in the prostate; rather, it is randomly arrayed throughout the stroma. Prostatic concretions (C) are again evident in the lumina of alveoli, in one instance compressing the epithelium to a degree that makes it nearly unrecognizable. The lower inset, corresponding to the smaller rectangle, clearly demonstrates the pseudostratified columnar nature of the prostatic epithelium (Ep). Well-delineated basal cells (arrowheads) are seen along with the taller columnar secretory cells. A


Histology_Ross

Histology_Ross. clearly demonstrates the pseudostratified columnar nature of the prostatic epithelium (Ep). Well-delineated basal cells (arrowheads) are seen along with the taller columnar secretory cells. A small blood vessel immediately subtending the epithelium is recognizable by the red blood cells in its lumen. A lymphocytic infiltration appears to fill the stroma along the lower border of this image suggesting an inflammatory process occurring in the prostate gland.


Histology_Ross

Histology_Ross. PLATE 90 KEY BV, blood vessel C, prostatic concretion Cap, capsule Ep, epithelium L, lymphocytes SM, smooth muscle arrows, inactive alveoli arrowheads: top fgure, “epithelial islands”; bottom figure, basal cells


Histology_Ross

Histology_Ross. The seminal vesicles are evaginations from the end of each ductus deferens that form tightly coiled tubes. Although sections through this structure may show many lumina, they are all profiles of a single continuous tubular lumen. The seminal vesicles are lined with a pseudostratified columnar epithelium that closely resembles that of the prostate gland. The secretion of the seminal vesicles is a whitish yellow viscous material that contains fructose, other simple sugars, amino acids, ascorbic acid, and prostaglandins. Although prostaglandins were first isolated from the prostate gland (hence the name), they are actually synthesized in large amounts in the seminal vesicles. Fructose is the primary nutrient source for the sperm in the semen. The mucosa rests on a thick layer of smooth muscle that is directly continuous with that of the ductus deferens, from which the seminal vesicle evaginates. The smooth muscle consists of an indistinct inner circular layer and an outer longitudinal


Histology_Ross

Histology_Ross. that is directly continuous with that of the ductus deferens, from which the seminal vesicle evaginates. The smooth muscle consists of an indistinct inner circular layer and an outer longitudinal layer (compare with the three layers of the ductus epididymis and the ductus deferens, Plate 88), which are difficult to distinguish. Contraction of the smooth muscle coat during ejaculation forces the secretions of the seminal vesicles into the ejaculatory ducts. Beyond the smooth muscle is the connective tissue of the adventitia.


Histology_Ross

Histology_Ross. Seminal vesicle, human, H&E 30. This figure shows a cross section of a seminal vesicle. Because of the coiled nature of the vesicle, two almost distinct lumina, lying side by side, appear to be present. They are, however, connected so that, in effect, all of the internal spaces are continuous and what is seen here is actually a two-dimensional configuration reflecting coiling of the tube. The mucosa of the seminal vesicles is characterized by being extensively folded or ridged. The ridges vary in size and typically branch and interconnect with one another. The larger ridges may form recesses that contain smaller ridges, and when cut obliquely, these appear as mucosal arches that enclose the smaller folds (arrows). When the plane of section is normal to Mucosal folds, seminal vesicle, human, H&E 220.