Structure of the Male Reproductive System

Structure of the ph on the wholeic Reproepithelial ductive Sy stopNew chapter 35The Male Reproductive SystemINTRODUCTIONThe staminate productive system has ternion principal functionsThe differentiation and nutri manpowert of the primary and tributary call down char momenteristics under the influence of the horm unrivalled testosterone, made in the testes.Spermatogenesisthe creation of the potent gametes inside the testes.The penial delivery of sperm cell cell cellatozoan from the testes into the fe masculines vagina in the act of procreation. This includes penile erecting and interpellation.SYSTEM STRUCTUREThe masculine productive system comprises non only the male genitals, plainly in like manner the cranial structures that help regulate the per boundance of the male reproductive systemnamely, the hypothalamus and pituitary body body. At the hypothalamic and pituitary level, however, male and female anatomy and histology be much or less the same. For more(pr enominal) enlarge on the hypothalamic and pituitary structures involved in human reproduction, see Chapter 36. In the section that fol get-gos, we will center on the anatomy and histology of the testes, the penis, and the ductal connections betwixt the testes and penis.The TestesThe male gonads, or testes, ar suspended from the perineum in an external contracted sac called the scrotum ( jut out 37.1A). for severally one musket ball is about(predicate) 4 cm long, and the testes be perfused by the spermous arteries. The spermatic arteries are closely apposed with the spermatic venous plexus, and this close contact allows countercurrent heat qualify between artery and vein, cooling the descent that flows to the testes. Countercurrent heat exchange helps keep the testicular temperature cool bountiful for optimal spermatogenesis (1C to 2C cooler than body temperature). The external location of the testes in the scrotum serves as a second important cooling mechanism. Because the testes develop within the abdomen, they descend into the scrotum during foetal life, stretching the deep inguinal rings around week 28 of gestation and inhabiting the scrotum by birth. In nearly instances (3% of the time in full-term male infants), the testes do not descenda condition called cryptorchidism. Cryptorchidism must(prenominal)iness be corrected if the male is to deplete properly functioning, fertile gonads.The testes are composed of coiled seminiferous tubules embedded in connective interweave (see Figure 37.1B). The connective tissue, which realizes up about 20% of the testicular mass, comports Leydig cellular phones, which make testosterone. The seminiferous tubules, constituting 80% of the testicular mass, generate the sperm. The tubules contain two main cell types spermatogonia and Sertoli cells. Spermatogonia are the germ cells that undergo meiosis to give rise to spermatids, the immediate precursors to spermatozoa. The copious cytoplasm of the Sertol i cells only envelops and protects the spermatids, shut them off from any contact with the tubules outer ba sourcet membrane or channel add together. This Sertoli sheath then forms a blood-testis barrier to protect the male gametes from any harmful bloodborne agents, and to prevent the immune system from contend the unique sperm-specific proteins as though they were foreign antigens. By virtue of their position between the blood and the spermatids, the Sertoli cells too transport nutrients, oxygen, and hormones, such(prenominal) as testosterone, to the spermatids.Figure 37.1 Anatomy of the male reproductive system. A. Overview. B. A juxtaposed look at the testis. C. The ducts of the reproductive system shown in isolation. The ducts arising from both testes are depicted, converging on the bottom of the inning urethra inside the prostate gland.The spermatogonia sit outside the blood-testis barrier near the basement membrane. Here, they continuously conduct mitosis. The produc ts of mitosis are pushed toward the tubule lumen and undergo meiosis and differentiation into sperm cells. The Sertoli barrier is fluid and accommodates the passage of cells developing into spermatids. The testes make around 120 million sperm a day. As they differentiate, the sperm migrate into the tubule lumen for transport distally to the rete testis, a plexus of ducts that collects sperm from each of roughly 900 seminiferous tubules. The rete testis empties into the epididymis, a single coiled tubule running from the top of the testis down its posterior aspect. In the epididymis, sperm are stored and undergo maturation before continuing their voyage outside the testis.The Ducts and PenisEach epididymis leads to a long, straight tube called the vas deferens (see Figure 37.1C). The vas deferens from the epididymis of each testis rises in the scrotum, ranges laterally with the inguinal canals, runs along the pelvic wall toward the posterior, and descends along the posterior aspec t of the bladder. Here the two vas deferens tubes widen into ampullae, which are attached to glands called the seminal vesicles. (There are two seminal vesicles, one for each vas deferens.) The seminal vesicles secrete more than half the volume of the semen. The two ampullae each send an ejaculatory duct through the prostate gland, and the ejaculatory ducts join the urethra inside the tissue of the prostate gland. From this point onward, the male urethra serves as pop of both the reproductive and urinary tracts, unlike female anatomy, in which the reproductive and urinary tracts are completely separate. Male physiology ensures that micturition and ejaculation do not occur simultaneously.The urethra next passes through the muscle tissue of the urogenital diaphragm, a consciously controllable sphincter. Sitting just under the urogenital diaphragm are the bulbourethral glands (also called Cowpers glands), which lubricate the urethra with mucous secretion. Finally, the urethra enters the penis. The cylindrical penis houses the urethra in erectile tissue, which helps exertion the transition between the excretory and reproductive functions of the urethra (Figure 37.2). This erectile tissue contains cavernous sinuses that fill with blood under circumstances of change magnitude penile blood flow, leading to erection of the penis. When erect, the penis may be inserted into the vagina so that sperm may be delivered to the fallopian tubes.Figure 37.2 Cross-section of the penis.The erectile tissue is present in three cylinders inside the penis, each called a corpus cavernosum and together called the corpora cavernosa. Two of the corpora lie dorsally and are sheathe by the ischiocavernosus muscles. One lies ventrally and is sheathed by the bulbospongiosus muscle. The ventral corpus cavernosum is also called the corpus spongiosum, and it is special in that it contains the urethra and forms the glans penis, the spongy headway of the penis. The corpora are each supplied by a cavernous artery that gives out helicine arteries. The penis averages 8.8 cm (3.5 in) in duration when flaccid and 12.9 cm (5.1 in) when erect, indicating no correlation between flaccid and erect size.SYSTEM FUNCTION sightly as the female reproductive system is coordinated by the hypothalamus and pituitary, the activities of the male reproductive system are coordinated by the HPG axis, in this case the hypothalamic-pituitary-testicular (HPT) axis (Figure 37.3). (The gonadal HPT axis is not to be confused with the hypothalamic-pituitary- thyroid axis, also tagged HPT.) The male axis shares with the female the exact same hypothalamic hormone, gonadotropin- releasing hormone (GnRH), and the same pituitary gonadotropins, follicle-stimulating hormone (follicle-stimulating hormone) and luteinizing hormone (LH). (The gonadotropins are named for their female reproductive functions, but they act in the male nonetheless.) The same array of gonadal steroid hormones that is produced by th e ovary is also synthesized by the male reproductive system, but in different proportions. Because of differential expression of enzymes in the steroid synthesis pathway, the female gonad makes predominantly progesterone and estrogen, while the male gonad predominantly makes the androgen steroid hormone testosterone. Testosterone inhibits the secernment of GnRH, LH, and follicle-stimulating hormone in a classic negative-feedback loop.Figure 37.3 Hypothalamic-pituitary-testicular axis. Plus signs represent stimulation minus signs represent inhibition.The HPT AxisGnRH is the initial driver of testicular function. It is cloakd in a pulsatile fashion (one pulse every 1 to 3 hours) and distributes to the pituitary gonadotrophs through the hypothalamic-pituitary portal circula- tion. There, the releasing hormone stimulates the LH- and follicle-stimulating hormone-secreting cells. Each GnRH pulse directly prompts an LH pulse from the gonadotrophs. to a greater extent frequent or larger-a mplitude GnRH pulses result in more frequent or larger-amplitude LH pulses. GnRH also increases FSH release, but the correlation between GnRH and FSH release is not as exact.LH acts on the Leydig cells. The LH signal is transduced by a seven- transmembrane receptor linked through a G protein to adenylyl cyclase, which produces tenting. LH-dependent elevations in cAMP promote testosterone synthesis from cholesterol and promote the growth of Leydig cells. Testosterone synthesis is increased by the activation and increased expression of key proteins involved in steroidogenesis, such as the steroidogenic acute regulatory protein (StAR). StAR shuttles cholesterol into steroid-manufacturing cells. The Leydig cells of the testis are unique in their ability to make testosterone in large amounts (Figure 37.4). plot of ground the zona reticulata cells of the adrenal gland also make androgens, the adrenal pathway stops at androstenedione, the immediate precursor to testosterone. (Some encir cling(prenominal) tissues can make testosterone from androstenedione in small amounts.)FSH, meanwhile, binds to receptors on the Sertoli cells, activating the production of proteins involved in spermatogenesis. FSH also stimulates glucose metabolism, thereby providing energy to the sperm precursors. (Spermatogenesis will be discussed in more detail below.) Finally, FSH upregulates the expression of the androgen receptor in Sertoli cells, thereby potentiating the influence of testosterone upon spermatogenesis.Like all steroids, testosterone binds an intracellular receptor, which binds DNA arranging factors and influences gene expression. The distribution of testosterone receptors in the body tissues determines the targets of testosterone action. In addition, target tissues express an enzyme that converts testosterone to its more alive(p) form, dihydrotestosterone (DHT). This enzyme is 5-reductase. DHT binds more avidly to the androgen receptor than does testosterone itself. Testoste rone from the Leydig cells passes through the Sertoli cells and into the seminiferous tubules, where, alongside FSH, it promotes spermatogenesis. The Sertoli cells make androgen-binding protein (ABP), which helps them to retain testosterone. Testosterone also acts systemically, promoting growth and sustaining gene expression in many peripheral tissues. Testosterone is transported in the blood by commove hormone-binding protein (SHBP), also called sex hormone-binding globulin, a liver-produced carrier protein that is structurally similar to ABP. It is thought that testosterone and SHBP itself may act at cell membrane receptors, in addition to testosterones genomic effects. This is parallel to the genomic and nongenomic modes of signal transduction employed by thyroid hormone.Finally, testosterone inhibits GnRH and gonadotropin secretion. Thus, testosterone limits its own production and action. Inhibin from the Sertoli cells also inhibits the pituitary and hypothalamus. Inhibin is a TGF- glycoprotein hormone. Investigations suggest that additional feedback mechanisms link Sertoli cell behavior with Leydig cell behavior. Table 37.1 summarizes the actions of testosterone.Table 37.1 Testosterone ActionsThe Expression of Male Sex CharacteristicsThe male reproductive system begins to function during embryonic life. As soon as the testes form and are capable of secreting testosterone, the androgen begins to act on the body tissues. At this stage, the hormone differentiates the fetus into a male with the appropriate primary sex characteristicsthe male genitals. At puberty, testosterone causes sustained expression of the secondary sex characteristics, which are gender-based phenotypes other than the genitals, such as hairsbreadth growth, muscle development, and a low voice.Fetal Life and Infancy (Primary Sex Characteristics) While the testes do act in utero, they cannot act before they have organise, and they do not form right away. In fact, before 6 weeks of gestati on, the gonads of genotypically male or female embryos have not begun to differentiate into both ovaries or testes. The so-called orthogonal gonad has an inner medullary (male) and an outer cortical (female) layer. In addition, the anatomic precursors of both males (the Wolffian ducts) and females (the Mllerian ducts) are present. Only at 6 to 8 weeks of gestation is male cozy development initiated by the SRY gene, a gene on the short arm of the Y chromosome. SRY encodes a zinc find DNA-binding protein called testis determining factor (TDF). Under the influence of TDF, the medullae of the indifferent gonads develop while the cortices regress. The previously indifferent gonads differentiate into testes embryonic germ cells form spermatogonia, coelomic epithelial cells form Sertoli cells (6 to 7 weeks of gestation), and mesenchymal stromal cells form Leydig cells (8 to 9 weeks of gestation). straight off the testes can begin to act. The Sertoli cells secrete a Mllerian-inhibiting factor (MIF), which causes regression of the Mllerian ducts. Human chorionic gonadotropin (hCG)which is structurally related to LHstimulates the Leydig cells to proliferate and secrete testosterone. The testosterone is reduced to DHT in target tissues by 5-reductase. As long as target tissues contain the androgen receptor and 5-reductase, DHT induces those tissues to form the primary male sex characteristics, the male reproductive organs. Under the influence of DHT, the Wolffian ducts differentiate into the epididymis, vas deferens, and seminal vesicles. The genital tubercle transforms into the glans penis, the urethral folds grow into the penile shaft, and the urogenital sinus becomes the prostate gland. Finally, DHT causes the genital swellings to fuse, forming the scrotum.At its peak, the fetal testosterone level reaches 400 ng/dL, but by birth it falls below 50 ng/dL. There is a brief spike in the male infants testosterone level between 4 and 8 weeks afterward birth, but its fu nction is not well understood. Otherwise, the testosterone level tolerates low throughout childhood, until puberty.Puberty and Beyond (Secondary Sex Characteristics) Puberty is the ferment by which males and females achieve reproductive capacity, and it begins in both sexes with an increase in hypothalamic GnRH secretion. It is possible that this increase is in response to decreasing hypothalamic sensitivity to testosterones negative-feedback effects. As the child approaches adolescence, the hypothalamus gradually escapes inhibition and GnRH secretion rises. LH and FSH secretion in turn rise, and testosterone secretion from the testes increases. Gradual maturation of hypothalamic neurons probably plays a role in this pubertal change in GnRH secretion.Increased testicular production of testosterone and other androgens at puberty has a host of effects. The earliest one is enlargement of the penis and testes. From the beginning to the end of puberty, the testicular volume more than q uadruples. Spermatogenesis commences (with testosterone effects perhaps being most important on the spermatids), and the prostate gland is stimulated to grow. harvesting occurs in many tissues outside the reproductive system as well.Androgens are anabolic steroids they promote the reposition of energy in complex molecules. While androgens promote protein synthesis, an anabolic hormone like insulin has a greater effect on the formation of complex carbohydrates and fats. Increased protein synthesis is associated with the growth of skeletal muscle, bones, skin, and hair (pubic, axillary, facial, chest, arms, and legs) and the growth of the larynx (which deepens the voice and causes the thyroid cartilage, or Adams apple, to protrude). Men on average have around 50% more muscle mass than women they have stronger, denser bone matrices and thicker skin. Muscle does not contain 5-reductase, so it appears that testosterone, not DHT, promotes muscular protein anabolism. However, testosteron e or DHT may promote muscular anabolism via extramuscular effects, such as the stimulation of growth hormone and insulin-like growth factor (IGF-1) production.Collectively, the development of the secondary sex characteristics is called virilisation (after the Latin vir for man). It appears that while testosterone promotes all of these effectsgenital growth and spermatogenesis, hair growth, behavioral changes, and anabolism in peripheral tissuescertain androgen precursors, metabolic byproducts, and pharmaceutical androgen analogs preferentially serve peripheral anabolism. Many of these metabolites and drugs are abused by bodybuilders and athletes. (See Clinical Application Box The Use and Abuse of Anabolic Steroids.)Testosterone, combined with a genical predisposition, also influences hair growth on the head. Male-pattern baldness typically begins with a decrease in hair growth on the top of the head and progresses to a complete lack of hair growth adjoining from the top of the h ead down. Both factors, the androgens and the genes, are necessary for baldness to occur a man without the genetic predisposition will not become bald regardless of his testosterone level. A woman with the genetic predisposition will usually not become bald unless she suffers from excess androgen production. Similarly, a castrated male with low testosterone levels will not become bald even if he has a genetic predisposition. once testosterone levels rise during puberty, they reach a plateau and remain elevated until a man reaches his seventies, when they begin to decline. This event, called the male climacteric, may create some symptoms resembling those of female menopause. However, hormone replacement therapy (HRT) is not commonly used to parcel out these symptoms. One reason is that men in this age group are at increased assay for prostate cancer. Because testosterone has proliferative effects on the prostate, HRT might further increase the risk of prostate cancer. While testos terone does promote spermatogenesis, this testicular function is remarkably well preserved in men even after the climacteric.The Haploid Life Cycle in the MaleAs mentioned above, spermatogenesis begins with puberty and continues into the eighth decade of life. Spermatogenesis has three phases spermatocytogenesis, during which the primordial spermatogonia divide by mitosis and differentiate into spermatocytes meiosis, resulting in four haploid gametes called spermatids, each with a pass of the cytoplasm of the original spermatogonium (see Chapter 36) and spermiogenesis, during which the spermatids are nourished and physically reshaped by the surrounding Sertoli cells. The product of spermiogenesis is spermatozoa, or sperm (Figure 37.5). After spermiogenesis, the epididymis and reproductive tract glands help prepare the sperm for fertilization.Spermatocytogenesis and Meiosis The evolving group of cells spanning from spermatogonia to spermatozoa is sometimes called the spermatogenic s eries. Not all spermatogonia enter into the spermatogenic series. If they did, they would be consumedas happens to the oogonia in the ovary, eventually leading to menopause. Instead, the testis csontinually replenishes its own supply of spermatogonia. As they undergo mitosis, some of the new ones are committed to the spermatogenic series, while some remain undifferentiated. The undifferen- tiated stem cells are called type A spermatogonia, and the differentiated spermatogonia committed to becoming spermatocytes are called type B spermatogonia. at once this apportioning of mitotic products into one group or another occurs, spermatocytogenesis continues as follows. Type A spermatogonia remain on the outside of the blood-testis barrier, while type B spermatogonia cross it, becoming enveloped by the cytoplasmic processes of the Sertoli cells. These type B spermatogonia differentiate further and enlarge to become primary spermatocytes. The primary spermatocytes then enter meiosis, a pro cess that takes around 3.5 weeks to complete, almost all of which is spent in prophase (when the newly replicated chromosomes condense). Each primary spermatocyte divides into two secondary spermatocytes, which in turn divide again into a total of four haploid spermatids. Each spermatid contains both an X chromosome or a Y chromosome. The males gamete thus decides the sex of his offspring.Spermiogenesis Spermiogenesis begins once the spermatids are created and delivered into the embrace of the amoeboid Sertoli cells (Figure 37.6). The spermatid elongates and reorganizes its nuclear and cytoplasmic contents into a spermatozoon with a dis impact head and tail. The head consists of a condensed nucleus surrounded by a thin layer of cytoplasm. The assuagement of the retained cytoplasm and cell membrane is shifted toward the opposite end of the sperm, the tail. A large amount of the spermatids cytoplasm is shed into the surrounding Sertoli cell during spermiogenesis. As the transformed sperm is extruded into the seminiferous tubule lumen, the discarded cytoplasm remains embedded in the cytoplasm of the Sertoli cell, where it is ultimately phagocytized.Figure 37.6 SpermiogenesisThe structure of sperm cells enables them to swim up the female reproductive tract and fertilize oocytes. The tail of a sperm contains a flagellum for motility. Originating from one of the centrioles of the sperm cells, the flagellum consists of a exchange skeleton of microtubules called the axoneme. The axoneme is arranged in the ancient 9 + 2 pattern characteristic of eukaryotic cilia and flagella across all kingdoms and phyla of life 9 pairs of microtubules surrounding 2 central tubules, linked via a complex array of protein bridges. The sperm cells mitochondria aggregate along the proximal end of the flagellum and supply energy for movement to the flagellum. The flagellum enables the sperm to swim.The anterior two thirds of the head of the sperm cell is surrounded by a thick capsule kno wn as the acrosome, formed from the Golgi apparatus. The Golgi apparatus contains numerous hydrolytic and proteolytic enzymes, similar to those found in lysosomes, and ultimately facilitates the sperms penetration of the egg for fertilization. There is also evidence to suggest a role for the acrosomal enzymes in penetrating the mucus of the female cervix.Epididymal Sperm Maturation and Storage After spermiogenesis is complete, the sperm pass out of the testis (through the rete testis) and into the epididymis, where growth and differentiation continue. After the first 24 hours in the epididymis, the sperm acquire the potential for motility. However, the epithelial cells of the epididymis secrete inhibitory proteins that suppress this potential. Thus, the 120 million sperm produced each day in the seminiferous tubules are stored in the epididymis, as well as in the vas deferens and ampulla. The sperm can remain in these excretory genital ducts in a deeply suppressed and inactive state for all over a month without losing their potential fertility.The epididymis also secretes a special nutrient fluid that is ultimately ejaculated with the sperm and is thought to mature the sperm. This fluid contains hormones, enzymes (such as glycosyltransferases and glycosidases), and nutrients that are essential to achieving fertilization. The precise function of many of these factors is not known, but enzymes like gamma-glutamyl transpeptidase are thought to serve as antioxidants argue against mutations in the sperm.Potentiation in the semen The accessory genital glandsthe seminal vesicles, prostate gland, and bulbourethral glandsalso contribute to potentiation. During ejaculation, their secretions dilute the epididymal inhibitory proteins, allowing the sperms motile potential to be realized. In addition, the glands make individual contributions to sperm preparation and support. The seminal vesicles secrete semen, a mucoid yellowish material containing nutrients and sperm-ac tivating substances such as fructose, citrate, inositol, prostaglandins, and fibrinogen. Carbohydrates such as fructose appropriate a source of energy for the sperm mitochondria as they power the sperms flagellar movements. The prostaglandins are believed to concern the sperm by affecting the female genital tractmaking the cervical mucus more undetermined to the sperm, and dampening the peristaltic contractions of the uterus and fallopian tubes to prevent them from expelling the sperm.The prostate gland secretes a thin, milky, and alkaline fluid during ejaculation that mixes with the contents of the vas deferens. The prostatic secretion contains calcium, zinc, and phosphate ions, citrate, acid phosphatase, and various clotting enzymes. The clotting enzymes act with the fibrinogen of the seminal fluid, forming a weak coagulum that glues the semen inside the vagina and facilitates the passage of sperm through the cervix in larger numbers. The alkalinity imparted to semen by the pr ostate counteracts vaginal acidity, which is a natural defense against microbial pathogens and which can kill sperm or impair sperm motility. By titrating the acidity, the prostate ensures that the sperm can elude this antimicrobial defense.Capacitation in the Female Reproductive leaflet Ejaculated sperm is not immediately capable of fertilizing the female oocyte. In the first few hours after ejaculation, the spermatozoa must undergo capacitation inside the female reproductive tract. This is the final step in preparation for fertilization. First, the fluids of the female reproductive tract wash away more of the inhibitory factors of the male genital fluid. The flagella of the sperm hence act more readily, producing the whiplash motion that is needed for the sperm to swim to the oocyte in the fallopian tube. Second, the cell membrane of the head of the sperm is modified in preparation for the ultimate acrosomal reaction and penetration of the oocyte. Capacitation is an incompletely understood phenomenon.Fertilization Once capacitated, the spermatozoa travel to the oocyte. There is an enormous rate of attrition among the blows of millions of ejaculated sperm, and at most a few hundred reach the oocyte. However, the female reproductive tract is simultaneously increasing receptivity to the male gametes (see Chapter 36).When the few hundred sperm reach the egg, they begin to try to penetrate the granulosa cells surrounding the secondary oocyte. The sperms acrosome contains hyaluronidase and proteolytic enzymes, which open this path. As the anterior membrane of the acrosome reaches the zona pellucida (the glycoprotein coat surrounding the oocyte), it rapidly dissolves and releases the acrosomal enzymes. Within minutes, these enzymes open a pathway through the zona pellucida for the sperm cytoplasm to merge with the oocyte cytoplasm. From beginning to end, the process of fertilization takes about half an hour.Figure 37.7 Sexual response and changes in the penis.Pen ile Erection and EjaculationThe practice of cozy fertilization, in which the male deposits gametes directly into the reproductive tract of the female, is at least 300 million old age old. Early cartilaginous fishes probably were its innovators. These elasmobranchs retained their concepti internally until the eggs could be waterproofed and thus defend from the osmotic stress of seawater. Eventually, almost all the higher vertebrates would practice internal fertilization for the sake of defending the next generation.For this reason, the male vertebrate possesses a special apparatus for penetrating the body of the female and delivering semen to an internal location. There are two physiologic events crucial to this internal delivery of semen penile erection, which makes it possible for the penis to penetrate the vagina, bringing the urethral opening, or meatus, into close contact with the female cervix and ejaculation, in which the semen is secreted into the male reproductive ductal system, mixed with sperm, and then mechanically squirted out of the penis. Both of these events are initiated and controlled by the nervous system in connection with the subjective state of sexual arousal.Sexual Response in the Male William H. Masters and Virginia E. Johnson in 1966 described four phases of sexual response