BY 32 – Fall 2000

LECTURE 22: THE MALE REPRODUCTIVE SYSTEM

I. Overview:

The function of the male reproductive system is two-fold: the production and delivery of germ cells called spermatozoa and the production of hormones that not only affect reproductive function but also many other tissues and organs in the body. These hormones are in general called androgens, of which the primary androgen is testosterone. Both functions are largely carried out by an organ called the gonad, defined as the sex organ where germ cells are produced and hormone production takes place. In the male the gonad is called the testis.

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II. Anatomy of the Male Reproductive System:

1. Overview: The male reproductive system consists of a gonad called the testis, and a duct system that leads from the testis to the external environment (Fig 1 = Marieb, 4^th edition, 28.1). Among the components of this duct system are the epididymis, vas deferens, ejaculatory duct, and urethra. The urethra represents the common tube by which urine flows from the bladder to the environment and by which spermatozoa immersed in a fluid called semen travel to the environment during sexual stimulation. In addition to the duct system, there are also a number of exocrine glands along the way that secrete the various components of semen. These include the seminal vesicles, prostate, and bulbourethral glands. Finally, the testes and epididymis are contained within an outpocketing of the abdominal wall called the scrotum, and the urethra is largely contained within the penis.

2. Scrotum and Spermatic Cord: The scrotum is a sac of skin that hangs outside of the abdominopelvic cavity that contains the testes and epididymis (Fig 2 = Marieb, 4^th edition, 28.2). The blood vessels, nerves, and the portion of the duct system called the vas deferens form what is known as the spermatic cord and communicate with the pelvic cavity via the inguinal canal. A midline septum divides the scrotum into right and left halves. The scrotum serves a vital function for male reproductive function by keeping the contents of the scrotum 1-2 degrees cooler than core body temperature which is vital for normal spermatogenesis. This lower temperature is maintained through a combination of:

· The Pampiniform Plexus: is a complex of veins that surround the arteries in the spermatic cord so that heat conveyed in the artery is transferred to the veins, ensuring that temperature does not increase within the scrotum.

· The Location of the Scrotum: The fact that the scrotum and its contents are located outside of the abdominopelvic cavity means that they are not exposed to core body temperature. Furthermore the scrotum maintains temperature by responding to changes in ambient temperature. For example, when its cold, the scrotum is elevated closer to the body wall and the skin is wrinkled to minimize heat loss. By contrast, in hot conditions, the scrotum is smooth and allowed to hang down. These changes are largely the result of the dartos muscle (smooth muscle just under the skin which wrinkles the scrotum) and the cremaster muscle which is a group of skeletal muscle fibers from the internal oblique which elevated the scrotum.

3. The Testis: Each testis is only about 4 cm long and 2.5 cm wide. It is surrounded by a two-layered tunica vaginalis, derived from the peritoneum (Fig 3 = Marieb 28.3). Inside of this is a thick connective tissue capsule called the tunica albuginea which sends septa inward to subdivide the testis into lobules.

Seminferous Tubules: The main structural unit of the testis is the seminferous tubule (Fig 4), which consists of a simple columnar epithelium composed of cells called Sertoli cells which form a tubular structure.

In addition to these cells, there are numerous intercellular spaces created between adjacent Sertoli cells, in which are found the various stages of spermatogenesis. Sertoli cells are responsible for a number of functions related to spermatogenesis, such as providing nutrients and other factors needed by developing spermatocytes.

Blood-Testis Barrier: is created by tight junctions that form between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. This barrier in effect creates two types of compartments called the basal and adluminal compartments. While the basal compartment is continuous with interstitial fluids of the testis, the adluminal compartments are isolated allowing the developing germ cells to be exposed to a special microenvironment. The blood-testis barrier also affords protection against various pathogens, mutagens, and components of the immune system.
Leydig Cells: lie in interstitial spaces between seminiferous tubules. These cells secrete androgens, the main type being testosterone. Leydig cells are surrounded by capillaries.
Other Ducts within the Testis: Seminiferous tubules converge on structures called straight tubules which in turn converge on the rete testis, a network of channels found in mediastinum. The mediastinum is a region in which the tunica albuginea is thickened near where the testis meets the epididymis. Connecting the epididymis and the rete testis are a number of tubes called the efferent ductules.

4. Epididymis: also lies in the scrotum and consists of a highly coiled duct (often called the ductus epididymis). While the epididymis is only about 3.8 cm long, the duct is actually about 6 meters (=20 ft) long. The epididymis is subdivided into head, body and tail which become surrounded by an increasing thick layer of smooth muscle. The tail of the epididymis is continuous with the vas deferens. The duct is lined by a pseudostratified epithelium, in which the cells have non-motile stereocilia. The epididymus represents a storage organ for spermatozoa, and in addition the sperm finish their maturation, acquiring motility here.

5. The Vas Deferens and Ejaculatory Duct: is a highly muscular tube that begins at the epididymis and runs into the pelvic cavity through the inguinal canal. A total of 45 cm long, it is easily palpable in the spermatic cord increasing the ease of vasectomy, an operation in which the vas deferens is cut in the spermatic cord, rendering the individual infertile. At its termination at the prostate, it widens a bit forming a portion called the ampulla. At this point, it merges with the duct of the seminal vesicle to form the ejaculatory duct which traverses the prostate to end in the urethra.

6. Urethra: is subdivided into prostatic, membranous, and penile urethral portions. The prostatic portion is the first part that traverses the prostate and receives the ejaculatory ducts. As the urethra passes through the pelvic diaphragm, it is called the membranous part which then enters the penis forming the penile portion. It is lined by a transitional epithelium throughout its course.

7. Accessory Glands: are responsible for the bulk of seminal secretions and consist of:

Seminal Vesicles: paired glands that merge with the ampulla of the vas deferens. Their secretions account for about 60% of semen and include such components as fructose (energy source for sperm) and prostaglandins (affect the motility of the female reproductive tract). The secretions are somewhat alkaline which account for the overall slight alkalinity of semen, which is important to neurtralize the acidic conditions of the vagina. Spermatozoa function is inhibited at low pH.
Prostate: is a single gland that encircles the urethra as it passes down from the bladder. Most of the prostate contains glandular portions which account for about 30% of semen. Contained in their secretions are citric acid and several proteolytic enzymes. The prostate gland has a tendency to hypertrophy with age in men, causing problems with urination. Often, this can be an sign of prostatic cancer.
Bulbourethral Glands: small glands located below the prostate which produce a mucous type secretion which neutralizes the traces of acidic urine in the urethra.

8. The Penis: is the organ responsible for the delivery of male germ cells during intercourse. Together with the scrotum, the penis constitutes the male external genitalia as opposed to the other components of the male reproductive system which constitute the internal genitalia.

· The penis consists of root, body, and glans (Fig. 5 = Marieb, 4^th edition, 28.4). The skin covering the penis is loosely attached and forms a cuff of skin over the

· glans penis called the foreskin. Often this tissue is surgically removed shortly after birth in a procedure called circumcision.

· The penis consists of three long cylindrical bodies called corpora which represent erectile tissue. On the dorsal surface are the paired dorsal corpora cavernosa, while the single corpus spongiosum lies ventrally and contains the urethra. The beginning of the corpus spongiosum is enlarged forming the bulb of the penis while the distal portion is expanded to form the glans penis. The corpora cavernosa attach the penis to the pelvis via two crura at their proximal ends.

· Erectile tissue of the corpora consist of venous spaces which are normally empty because blood is shunted away. Upon sexual excitement, these channels fill, causing the penis to enlarge and become rigid in a process called erection.

III. Spermatogenesis:

1. Overview: In both sexes, the germ cell line differentiates quite early in embryonic development. These cells eventually migrate to the primitive gonad they proceed to divide forming the large numbers of germ cells. In the female, this process proceeds in shortly after in the early stages of embryonic development. In the male however, these cells remain inactive through the rest of embryonic and fetal development up until the time of puberty. At that point, the process of spermatogenesis begins and continues essentially undiminished through the life of the man. The entire cycle takes about 70 days and the various stages can be found within the intercellular compartments of the Sertoli cells (Fig 6 = Marieb, 4^th edition, 28.8). The result is a tremendous production rate, on the order of about 300 million spermatozoa per day. In the process, the diploid precursor cells are converted to haploid germ cells via the process of meiosis.

2. Stages of Spermatogenesis:

Spermatogonia: To support such large numbers, there must be a stem cell which divides by mitosis. This cell is called the spermatogonium, which is actually subdivided into several substypes. The actual cycling stem cell is called the type A pale spermatogonium which upon mitotic division forms one A pale cell and one type B spermatogonium. The A pale cells continue to divide whereas the type B cell goes on in the process. In addition here is a type A dark cell which

represents a reserve cell. All these forms are found in the basal compartments, but the B cell is the form which migrates into adluminal compartments.
Primary and Secondary Spermatocytes: The primary spermatocyte differentiates from the B spermatogonia and begin meiosis I which upon completion form secondary spermatocytes which immediately begin meiosis II to form spermatids.

Spermiogenesis: is the process by which haploid spermatids differentiate into spermatozoa (Fig. 7). In this process, the Golgi apparatus migrates to the front to form the acrosome; the centrioles migrate to the back to give rise to a flagellum; and the nucleus condenses. As a result, the spermatozoan consists of a head (nucleus and acrosome); midpiece (mitochondria) and tail (flagellum which provides motility).

IV. Endocrine Regulation of Male Reproductive Function

1. Overview: The process of spermatogenesis and all other aspects of male reproductive function depend on the presence of hormones produced by the hypothalamus, the anterior pituitary, and the testis forming what is known as the hypothalamic-pituitary-testis axis (Fig. 8 =Tortora and Grabowski, 9^th edition, 28.9). Failure of any component of this system will result in infertility, loss of secondary sex characteristics, and if occurring embryonically failure to develop into a male. Furthermore, this axis is subject to feedback regulation through which the various hormones levels are controlled. We will now consider each component in turn.

2. The Hypothalamus: Certain neurons of the hypothalamus release gonadotropin releasing hormone (GnRH) into the hypothalamic-pituitary portal system where it then travels to the anterior pituitary to affect the secretion of pituitary hormones called gonadotropes.

3. Anterior Pituitary: Cells of the anterior pituitary called gonadotropes respond to GnRH by increasing secretion of two hormones called follicle stimulating hormone (FSH) and luteinizing hormone (LH). These hormones, together known as gonadotropins are released into the blood stream where they circulate to end in the testis to interact with their respective target cells.

4. Testis: The target cells for gonadotropins are:

Leydig cells: are the target cell for LH and in response increase their secretion of testosterone. Some of this testosterone remains locally to affect Sertoli cells, whereas much of it is released into the blood stream where it circulates to affect other organs of the male reproductive system as well as other tissues and organs.
Sertoli cells are the target cell for FSH and in response increase functions which support spermatogenesis. Actually testosterone from Leydig cells and FSH together result in a number of changes such as an increase in the amount of androgen binding protein (which chaperones testosterone to developing spermatocytes and throughout the male reproductive tract) and increases in metabolic support to spermatocytes.

5. Feedback Regulation: Testosterone inhibits release of GnRH from the hypothalamus and LH release from the pituitary. Interestingly, it does not affect FSH secretion at the level of the pituitary, and only does so indirectly by its effect on GnRH. Instead FSH secretion is inhibited by a regulatory molecule released from Sertoli cells called inhibin.

6. Effect of Androgens: Testosterone and other androgens interact with a large variety of target cells, but all function by combining with an intracellular receptor called the androgen receptor. In some target cells, the testosterone is converted to another potent androgen called dihydrotestosterone (DHT) in a process catalyzed by an enzyme called 5a reductase. DHT interacts with the same androgen receptor, which functions by combing to the target cell DNA and affects gene transcription. Among the effects of androgens in the body are:

Development of the male internal and external genitalia in embryonic and fetal development.
Development of male secondary sexual characteristics (beard, deep voice, etc)
Anabolism of various tissues such as an increase in muscle and bone mass, etc.
Development of sexual function: including stimulating spermatogenesis and supporting male sex drive (libido).

V. Male Sexual Response:

1. Erection: Normally the penis is flaccid because the venous spaces in erectile tissues are empty as a result of constriction of the arteries supplying these spaces. As a result blood is shunted via arterio-venous channels thereby bypassing these regions. Upon sexual excitement, mediated by the parasympathetic nervous system, these arteries dilate allowing these venous spaces to fill with blood giving rise to an increase in pressure and an enlargement of the penis – called erection. This vasodilation is mediated by release of nitric oxide, a potent vasodilator. The parasympathetic nerves also stimulate the secretions of the bulbourethral glands which produce mucus which not only neutralizes the acidic urine which may be present, but also results in release of this mucus from the penis aiding in lubrication. A variety of inputs including sensory and mental can lead to stimulation of vasodilatory parasympathetic nerves leading to erection. Failure to achieve an erection is called impotence which can result from a variety of factors ranging from vascular, nerve, psychological, or even temporary factors such as alcohol or certain drugs.

2. Ejaculation: actually consists of two distinct phases called emission and ejaculation, both under the control of the sympathetic nervous system. When sexual excitement reaches a maximum, there is a massive discharge of the sympathetic system which results in:

Emission: involves contraction of smooth muscle of the vas deferens which propels the spermatozoa forward through the ejaculatory duct into the prostatic urethra. Shortly after, the seminal vesicles contract forcing their contents forward followed by the prostate. These materials all mix in the prostatic urethra.
Ejaculation Proper: Due to stretch of the prostatic urethra, a second wave of nerve impulses pass to skeletal muscles associated with the bulb of the penis called the bulbospongiosus muscles. Contraction of these muscles forces the contents (semen) out the end of the penis. Another aspect is that the external urethral sphincter contracts preventing the semen from passing into the bladder.