1. The Essence of Sex
Reproduction is one of the most fundamental properties of all living things. Many organisms reproduce simply by fission (splitting into 2) or by budding off miniature replicas of themselves. These are asexual processes that produce exact genetic copies of the parent. Most organisms, however, reproduce sexually. Sexual reproduction does not necessarily entail copulation or even physical contact between the parents – many species merely shed sex cells into the sea and the parents never met. Thus, the reproductive system is not essential for survival, but is necessary for survival of the species and has a profound impact on a person’s life.
The essence of sexual reproduction is that each offspring has 2 parents and a combination of genes from both. Thus, the offspring is not genetically identical to their parents and usually not even to each other. Genetic diversity provides the foundation for survival and evolution of a species and has been such a substantial advantage that the great majority of organisms employ it.
2. General Terminology and Concepts
Human reproduction employs fertilization and depends on the integrated action of hormones, the nervous system and the reproductive system. The reproductive system includes the following.
The primary sexual organs are the testes and ovaries. Both are mixed glands i.e. they produce both sex hormones and gametes. The secondary sexual organs (a.k.a. accessory organs) are the system of ducts (in both) and the breasts (in females). The system of ducts is a channel through which the sperms and ova are transported and the glands lining or emptying into the ducts are also seen. The breasts are involved in the lactation after childbirth. The perineal structures are the external genitalia.
In a nutshell, the male and female reproductive systems are functionally quite different.
In an adult male, the testes or male gonads, secrete sex hormones called androgens (principally testosterone) and produce one-half billion of sperm each day. During emission, mature sperm travel along a lengthy duct system, where they are mixed with secretions of accessory glands. The mixture created is known as semen. During ejaculation, the semen is expelled from the body.
In an adult female, the ovaries or female gonads, typically release only one immature gamete, an oocyte per month. This gamete travels along short uterine tubes (oviducts) that end in the muscular uterus. A short passage way, the vagina, connects the uterus with the exterior. During the sexual act, ejaculation introduces semen into the vagina, and the sperm ascends the female reproductive tract. If fertilization occurs, the uterus will enclose and support a developing embryo as the embryo grows into a fetus and prepares for eventual delivery.
3. The Male Reproductive System
In the male, the urinary system is closely associated with the reproductive system. The urethra is a common passage for both urine and semen. Hence, the urinary and reproductive systems are usually considered together as the male urinogenital system.
The main reproductive role of the human male is to produce sperm and deliver them to the vagina of the female. In short, it produces sperms in the testes, delivers sperms in a liquid medium to the vagina during copulation and produce the chief male sex hormone, testosterone.
4. Anatomy of the Male Reproductive System
4.1 Testes
The paired testes are the male reproductive organs (gonads) which produce sperm. Testes are often called testicles. In Latin, testis means witness. The paired testes were believed to bear witness to a man’s virility. Each testis is enclosed within a scrotum. The testes complete their descent into the scrotum shortly before or after birth.
Interestingly, if the testes remain in the abdominal cavity instead of descending on schedule, surgery is usually performed during early childhood. The condition is called cryptochidism. If the condition is not corrected, the testes will produce testosterone but no sperm will develop, resulting in sterility. In addition, the risk of testicular cancer increases.
The scrotum is a pouching of the abdominal wall, consisting of loose skin and superficial fascia. It is the supporting structure of the testes. It is also isolated from the body wall. This provides the testes with an optimal temperature of 35oC for production and sperm storage. At suboptimal temperature, scrotal muscles contract involuntarily to bring the testes to the heat of the body. At super-optimal temperatures, they relax.
One testis (usually the left) hangs lower than the other, so the testes do not collide uncomfortably during normal activities. Because the testes hang outside the body, their temperature is about 2 degrees cooler than the body temperature. The lower temperature is necessary for active sperm production and survival. The sperm remain non-viable if they are retained inside the body cavity. For the same reason, a fever can kill hundreds of thousands of sperms, temporarily decreasing a man’s fertility. In warm temperatures, the skin of the scrotum hangs loosely, and the testes are held in a low position. In cold temperatures, the cremaster muscles under the skin of the scrotum contract and pull the testes closer to the warm body. In this way, the temperature of the testes remains somewhat constant. Sweat glands also help cool the testes.
4.1.1 Structure and Histology of the Testes
Each testis is oval-shaped and measures about 4.5 cm long and 2.5 cm wide in an adult. Below is a relation of its external structural features to its functions.
The tunica albuginea is a fibrous sac (made up of connective tissue), it functions to enclose the testis. The septum is an extension of the tunica albuginea into the testis, dividing it into 2 compartments. The lobules are compartments of the testis as divided by the septum.
4.1.1.1 Seminiferous Tubules
Each testis contains over 800 tightly coiled seminiferous tubules. Its function is to produce thousands of sperms each second in a healthy man. The walls of the seminiferous tubules are lines with germinal tissue which contains 2 types of cells. The spermatogenic cells include the spermatogonia, spermatocytes and the spermatids. They eventually develop into mature sperm. The development of sperm, or spermatogenesis, is discussed later. There are also sustentacular cells (sertoli cells) which are the nutritive cells. All spermatogenic cells are attached to the sertoli cells.
4.1.1.2 Leydig / Interstitial Cells
They are endocrine cells found in between seminiferous tubules. They secrete the male sex hormone called androgens, of which testosterone is the most important.
4.1.2 Castration
The removal of testes is called castration. Because a castrated male will not produce testosterone, he will eventually lose his sex drive. However, erection of the penis may still be possible after castration. A male who is castrated before puberty will gradually aquire feminine characteristics as fatty deposits in the breast and hips, lack facial hair and smooth skin texture. If an adult male is castrated, he will usually lose his facial hair and his bones and muscles will probably diminish in thickness and size, but other feminine characteristics will be minimal. Testosterone therapy may reduce these physical problems, but it cannot restore fertility.
4.2 Accessory Ducts
The testes produce physically mature spermatozoa that are as yet, incapable of successful fertilization. The other portions of the male reproductive system are responsible for the functional maturation, nourishment, storage and transport of spermatozoa.
The short tubuli connecting ends of the seminiferous tubules to the central region of the testes is called the rete testis.
10 – 20 vasa efferentia (a.k.a. efferent ductules) collect and transfer sperms form the rete testis to the head of the epididymides. The vasa efferentia have fluid currents created by cilia lining them to transfer the immobile spermatozoa.
Seminiferous tubules secrete fluids that are reabsorbed at the head of the epididymides to concentrate the sperms and allow maturation. The matured sperms are then transported to the base of the epididymides. Transport along the epididymides involves fluid movement and peristaltic contractions of smooth muscles in the walls of the epididymides. At the base, the spermatozoa are stored temporarily before entering the vas deferens.
The functions of the epididymides are as follows. They monitor and adjust the composition of the fluid produced by the seminiferous tubules. They act as a recycling centre for damaged spermatozoa. They store and protect spermatozoa and facilitate their function and maturation. A spermatozoon passes through the epididymis in about 2 weeks and completes its maturation at this time. Although spermatozoa leaving the peididymis are mature, they remain immobile.
The vas deferens is a straight tube and forms the spermatic cord with the spermatic artery and vein. It functions to convey spermatozoa to the ejaculatory duct. By the time spermatozoa enter the vas deferens, they are mature but still immobile. To be mobile, sperms must be mixed with seminal fluid.
The ejaculatory duct is posterior to the urinary bladder and functions to eject sperms into the prostatic urethra.
The urethra is the terminal duct of the system and serves as a common passageway for both sperms and urine.
4.3 Accessory Glands
Fluids contributed by the seminiferous tubules and epididymis account only for 5% of the semen. The rest of the 95% are from the accessory glands. The following are the functions of the glands. They activate spermatozoa, they provide the nutrients the sperms need for motility, they propel sperms and fluids along the reproductive tract mainly by peristaltic contractions and finally, they produce buffers that counteract the acidity of the urethral and vaginal environments.
4.3.1 Seminal Vesicles
They are paired glands with a length of 15 cm and lie below and behind the bladder. They produce the seminal fluid; 60 – 70 % of the semen. Its composition has a pH of about 7.4 and consists of fructose, mucus, citrate, ascorbic acid, prostaglandins, and fibrinogen.
Its alkalinity helps neutralize acids in the secretions of the prostate gland and within the vagina. Fructose is a source of energy for the sperms. It acts as an activator for previously inactive but functional sperms as it causes them to become motile. Prostaglandins aids in fertilization by reacting with the cervical mucus making it more receptive to sperm movements and for stimulation of smooth muscle contractions along the male and female reproductive tracts. Fibrinogen, which after ejaculation, forms a temporary clot within the vagina. This makes it easier for uterine contractions to move the semen.
4.3.2 Prostate Glands
These are single doughnut-shaped glands. They produce 20 – 30% of the semen; a thin milky secretion called prostatic fluid. The pH is 6.5 due to citric acid. Its composition is mucus, citric acid, proteolytic enzymes and anti-bacterial substances.
The slight alkalinity helps to neutralize the acidity of the vagina, making sperms more active. The proteolytic enzymes are important for sperm motility. The anti-bacterial substances help prevents urinary tract infections in males.
4.3.3 Bulbourethral (Cowper’s) Glands
They are paired, round glands situated at the base of the penis. They secrete thick, viscous alkaline mucus into the spongy urethra. This helps to neutralize the acidity of any remaining urinary acids. They also provide some lubrication for the tip of the penis, the glans, during sexual intercourse.
4.4 Semen
It is composed of sperms plus the secretions of the accessory glands. Sperms only make up about 1% of the semen. The rest is fluid from the accessory glands, which provides fructose to nourish the sperms, an alkaline medium to help neutralize urethral and vaginal acidity that could otherwise inactivate the sperms, and buffering salts and phospholipids that make the sperm motile.
Odour of semen is caused by amines, which are produced in the testes, The average ejaculation produces about 3 to 4 ml of semen and contains 300 to 500 million sperms.
5. Sperm Production and Development (Spermatogenesis)
Sperm cells, or spermatozoa, are produced by the process of spermatogenesis. It begins at the outermost layer of cells in the seminiferous tubules and proceeds towards the tubular lumen. Stem cells (spermatogonia) divide by mitosis to produce generations of daughter cells, some of which differentiate into spermatocytes. Then, through meiosis, spermatocytes give rise to spermatids (undifferentiated male gametes). At each step of the process, the daughter cells move closer to the tubular lumen. The spermatids subsequently differentiate into spermatozoa by the process called spermiogenesis.
Spermiogenesis ends as the physically mature spermatozoa lose contact with the wall of the seminiferous tubule and enter the fluid of the lumen. Spermiogenesis is the last step of spermatogenesis.
5.1 Summary of Events in the Seminiferous Tubules
A histological section of an adult testis shows that most of the cells making up the epithelial walls of the seminiferous tubules are in various stages of cell division. These cells, collectively called spermatogenic cells give rise to sperm via the series of cellular divisions and transformations as explained below.
5.1.1 Mitosis of Spermatogonia
This is the process of forming spermatocytes. The outermost and least differentiated tubule cells, which are in direct contact with the epithelial basal lamina, are stem cells called spermatogonia. The spermatogonia divide more or less continuously by mitosis and, until puberty, all the daughter cells become new spermatogonia. Spermatogenesis begins during puberty, and from then on, each mitotic division of a spermatogonium results in 2 distinctive daughter cells – types A and B. The type A daughter cells remains at the basement membrane to maintain the germ cell line. The type B cell gets pushed towards the lumen, where it becomes a primary spermatocyte destined to produce 4 sperms.
5.1.2 Meiosis
This changes spermatocytes to spermatids. Each primary spermatocyte generated during the first phase undergoes meiosis I, forming 2 smaller haploid cells called secondary spermatocytes. The secondary spermatocytes continue on rapidly into meiosis II and their daughter cells, called spermatids, can be seen as small round cells with large spherical nuclei closer to the lumen of the tubule.
5.1.3 Spermiogenesis
This changes spermatids to sperms. Although each spermatid has the correct chromosomal number for fertilization, it is non-motile. It still must undergo a streamlining process called spermiogenesis, during which it sheds its superfluous cytoplasmic baggage and fashions a tail. The resulting sperm has 3 major regions: a head, a mid-piece, and a tail, which corresponds roughly to genetic, metabolic, and locomotive regions respectively.
5.2 Anatomy of the Mature Sperm, Spermatozoa
A mature sperm has the following characteristics. Its life expectancy is about 48 hours. A sperm is one of the smallest cells in the body. Its length form the tip of the head to the tip of the tail is about 0.05 mm. Although it appears to be structurally simple, each sperm requires more than 2 months for its complete development.
The principal locomotory function of the sperm is to cluster around the oocyte and to orientate themselves prior to penetration of the oocyte membrane.
5.2.1 The Head of the Sperm
It is a flattened ellipse. At the tip of the head, there is an acrosome containing several enzymes that help the sperm penetrate an egg. In the centre of the head, there is the compact nucleus containing the chromosomes. In fact, DNA accounts for most of the dry mass of the head. A mature sperm lacks an endoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, inclusions and many other intercellular structures. Because the cell does not contain glycogen or other energy reserves, it must absorb nutrients from the surrounding fluid. The head contains 23 chromosomes which will be transported to the egg nucleus upon fertilization and eventually form 46 chromosomes in the zygote.
5.2.2 The Middle Piece of the Sperm
It is a short neck attached to the head. It contains both centrioles of the original spermatid. The microtubules of the distal centriole are continuous with those of the middle piece and tail. The middle piece consists of mainly mitochondria. Its function is to supply ATP to provide energy for movement of the tail.
5.2.3 The Tail of the Sperm
It is the only flagellum of the human body. The beating movement of the undulating tail drives the swimming sperm forward in the liquid medium. This ability to swim is called motility and is essential for male fertility.
5.3 Spermatogenesis and Sustentacular (Sertoli) Cells
Sustentacular cells play a key role in the process of spermatogenesis. These cells have 7 important functions that directly or indirectly affect mitosis, meiosis and spermiogenesis within the seminiferous tubules.
5.3.1 Maintenance of Blood-Testis Barrier
Sertoli cells are tightly connected to each other, by tight junctions, to the spermatogonia and to the basement membrane of the seminiferous tubules to form the blood-testis barrier.
Rather like a rubber ground sheet, this interlocking barrier prevents large molecules seeping to and fro between the central spaces of the seminiferous tubules and surrounding tissues, including the bloodstream. Thus the seminiferous tubules are isolated from the general circulation by a blood-testis barrier comparable in function to the blood-brain barrier.
Due to the secretory actions of the Sertoli cells, fluid found within the tubules is very different from the outside. It is rich in testosterone, potassium and the amino acids, aspartic acid and glutamic acid, which are all needed for sperm development.
The blood-testis barrier is important for maintaining these different concentrations of substances within the tubules. The Sertoli cells can pump fluid into the tubular space against a high pressure. If a blockage prevents fluid flowing from the tubules into the epididymis, secretion still continues, so the tubules blow up to the point where blood supply is cut off. This can lead to pressure damage, shrinkage and even death of tubular cells.
Perhaps, the most important function of the blood-testis barrier is that it prevents sperm fragments formed during development from accidentally entering the circulation and triggering the formation of anti-sperm antibodies. It also protects young sperm from attack by blood-borne infections or poisonous molecules. If the barrier is disrupted, for example by injury or vasectomy, so that sperm and blood can mix, the sperm are often misinterpreted as foreign by the immune system. Anti-sperm antibodies are made and this can obviously result in sub-fertility.
5.3.2 Support of Mitosis and Meiosis
Spermatogenesis depends on the stimulation of sustentacular cells by circulating FSH and testosterone. Stimulated sustentacular cells then in some way promote the division of spermatogonia and meiotic divisions of spermatocytes.
5.3.3 Support of Spermiogenesis
Spermiogenesis requires the presence of sustentacular cells. These cells surround and enfold the spermatids, providing nutrients and chemical stimuli that promote their development.
5.3.4 Secretion of Inhibin
Sustentacular cells secrete inhibin, a peptide hormone, in response to factors released by the developing sperm. Inhibin depresses the pituitary production of FSH and perhaps the hypothalamic secretion of GnRH. The faster the rate of sperm production, the greater the amount of inhibin secreted. By regulating FSH and GnRH, the sustentacular cells provide feedback control of spermatogenesis.
5.3.5 Secretion of Androgen-Binding Protein (ABP)
ABP binds androgens (primarily testosterone) in the fluid contents of the seminiferous tubules. This protein is thought to be important in elevating the concentration of androgens within the tubules and stimulating spermiogenesis. The production of ABP is stimulated by FSH.
5.3.6 Secretion of Mullerian – Inhibiting Factor (MIF)
MIF is secreted by sustentacular cells in the developing testes. This hormone causes regression of the fetal Mullerian ducts, passageways that in females participate in the formation of the uterine tubes and uterus. Inadequate MIF production during development leads to retention of these ducts and failure of the testes to descend into the scrotum.
5.3.7 Phagocytosis of Defective Sperms
There is the phagocytosis of defective sperms carried out by the sustentacular cells.
6. Hormones and the Male Reproductive Function
6.1 Brain-Testicular Axis
Hormonal regulation of spermatogenesis and testicular androgen production involves interactions between the hypothalamus, anterior pituitary gland and the testes, a relationship sometimes called the brain-testicular axis. The sequence of regulatory events is a follows.
The hypothalamus releases GnRH which controls the release of FSH and LH. GnRH reaches the anterior pituitary cells via the blood of the hypophyseal portal system.
Binding of GnRH to pituitary cells (gonadotrophs) prompts them to secrete FSH and LH into the blood.
FSH stimulates spermatogenesis in the testes indirectly by stimulating the sustentacular cells to release androgen binding protein (ABP). ABP prompts the spermatogenic cells to bind and concentrate testosterone which, in turn, stimulates spermatogenesis. Thus FSH makes the cells receptive to testosterone’s stimulatory effects.
LH binds to the interstitial cells and stimulates them to secrete testosterone (and a small amount of estrogen). LH is therefore sometimes called interstitial cell-stimulating hormone (ICSH) in males. Locally, testosterone serves as the final trigger for spermatogenesis. Testosterone entering the bloodstream exerts a number of effects at other body sites.
Both the hypothalamus and the anterior pituitary are subject to feedback inhibition by blood-borne hormones. Testosterone inhibits hypothalamic release of GnRH and may act directly on the anterior pituitary to inhibit gonadotropin release.
The amount of testosterone and sperm produced by the testes reflects a balance among three sets of hormones. They are the gonadotropins (which directly stimulate the testes), GnRH (which indirectly stimulated the testes via its effect on FSH and LH release) and testicular hormones (testosterone and inhibin), which exert negative feedback controls on the hypothalamus and anterior pituitary. Since the hypothalamus is also influenced bu input from other brain areas, the whole axis is under CNS control. In the absence of GnRH and gonadotropins, the testes atrophy, and for all practical purposes, sperm and testosterone production ceases.
6.2 Mechanism and Effects of Testosterone
Testosterone
is produced by the testicular Leydig cells. Like all steroid hormones, it is
synthesized from cholesterol, as are the female hormones estrogen and
progesterone. Leydig cells contain a high concentration of the enzymes required
to direct cholesterol through the testosterone-yielding pathway. Once produced,
some of the testosterone is secreted into the blood, where it is transported,
primarily bound to plasma proteins, to its target sites of action. At the
target cells, it exerts it effects by activating specific genes to transcribe
mRNA molecules, which results in enhanced synthesis of certain proteins within
the target cells. A substantial portion of the newly synthesized testosterone
goes into the lumen of the seminiferous tubules, where it plays an important
role in sperm production.
