Male Reproductive Development

The main functions of the male and female reproductive systems include the production of gametes, secretion of sex hormones (e.g. estrogen, progesterone and testosterone), providing a safe site for fertilization and development of the embryo and fetus, nourishment of the developing embryo and fetus, giving birth to a newborn at the end of gestation, and breastfeeding the newborn after birth. All of these functions excluding the production of male gametes (sperms) and male sex hormone (testosterone) and carried out by the female reproductive system. The male reproductive system produces enormously large numbers of motile gametes (sperms) on a daily basis compared to much fewer nonmotile female gametes (egg cells) that diminish in number with age and at the end are lost altogether. After puberty, the female reproductive system undergoes periodic functional changes; such periodic changes do not occur in the male reproductive system. 

The male reproductive system, also known as male genital system, consists of the testis, epididymis, vas deference, the seminal vesicles, the prostate, Cowper’s gland, the urethra and penis. Its main functions include the production, maintenance, and transportation of the gametes (spermatozoa) and production of the seminal fluid that carries and protects the spermatozoa, and as well the ejection of sperms at the end of a sexual relation. Moreover, the male reproductive system produces and secretes the male sex hormone (the testosterone) which responsible for maintenance of the male reproductive system. Testosterone is responsible for descent of the testes, maintenance of spermatogenesis, and enlargement of the penis. It also has other roles that include eliciting sex drive (libido), building muscle mass and strength, and maintenance of bone density. It is also involved in regulation of the secondary male characteristics, including male body hair patterns, vocal changes, and voice deepening. Testosterone also has anabolic effects that include stimulation of protein synthesis needed for growth of  skeletal muscle. Testosterone also stimulates erythropoiesis, which results in higher hematocrit values in males as compared to females. Testosterone levels tend to drop with age; accordingly, older men tend to experience a decrease in testicular size, a drop in libido, lower bone density, muscle mass decline, increased fat production, and decreased erythropoiesis, leading to possible anemia. 

Fig. 1.1. The illustration shows the various components of the male reproductive system.

The Male Gonad

The testis or testicle is the male gonad. Men possess two testicles which lie within a common sac called the scrotum which is a saccular extension of the anterior abdominal wall. Each testicle (testis) is an ovoid organ that measures about 5cm in length in adults. Each is surrounded by a thick tough fibrous connective tissue capsule known as the tunica albuginea. The posterior part of the tunica albuginea is thickened to form the mediastinum testis. Thin fibrous septa radiate from the mediastinum testis, dividing the testis into inconspicuous lobules. Each lobule contains 1-4 seminiferous tubules, separated by a loose connective tissue interstitium, which contains interstitial Leydig cells, blood vessels and nerves.

Fig. 1.2. The illustration on the left shows the surface morphology of the testis, epididymis, and vas deferens, whereas that on the right shows the component of the testis, the covering tunica albuginea, and connections of the testis and the epididymis. The tunica albuginea as seen on the left imparts a smooth appearance to the surface to the testis.

Tissues of the Testis

Histologically, the testis comprises, like most other body organs and glands of the body, comprises two tissues: a parenchyma and a stroma.

The parenchyma of the testis (testicular parenchyma) is made epithelial cells and sex cells.  The vast majority of the parenchymal cells are arranged into slender tortuous tubular structures known as seminiferous tubules. A minor proportion of the parenchymal cells are present in small clusters in between the seminiferous tubule in the form testosterone producing endocrine cells known as Leydig cells.

The stroma of testis is made of a capsule and an interstitium. The capsule is a tough dense fibrous connective tissue investment that protects the tissues of testis and give the testis a firm texture. It is covered anteriorly and on the sides by a serous membrane called the tunica vaginalis, which is derived from the peritoneum. The testicular interstitium, on the other hand,  is a loose areolar connective tissue; it occupies the spaces between the seminiferous tubules. The interstitium is made of an amorphous ground substance, fine collagen type1 fibers, reticular fibers, elastic fibers, fibroblasts, mesenchymal cells, macrophages and few mast cells. It contains blood vessels, lymph vessels and nerve fibers, in addition to the interstitial endocrine cells of Leydig. The interstitium also contains specialized cells called myofibroblasts that encircle the seminiferous tubules. Myofibroblasts are contractile cells that are often arranged in layers and help to expel the sperm out the seminiferous tubules into the excurrent ducts of the testis.

The testicular stroma plays a major role in the normal functioning of the testis; it provides protection, mechanical support to the seminiferous tubules and blood vessels, produces testosterone by its interstitial cells of Leydig cells, and augment the blood-testis barrier made by Sertoli cells.

Interstitial Leydig Cells

Leydig cells are PAS+ hormone producing cells present in the testicular interstitium. They secrete testosterone, the male sex hormone. Leydig cells are furnished with all organelles that are necessary for the synthesis and secretion of steroid hormone (testosterone). These organelles include sER (where steroids are synthesized), Golgi complexes (where the hormone is packaged) and secretory vesicles which transfer the hormone to the surface cell membrane where it is secreted by exocytosis. In older people, Leydig cells contain characteristic cytoplasmic inclusions known as crystals of Reinke. These inclusions are rod shaped structures, usually arranged in a linear pattern. Crystals of Reinke are of unknown functions; probably they are a by-product of the process of testosterone production.

Fig. 1.3. An H&E-stained section (left) and an illustration (right) showing histological features of the seminiferous tubules and the testicular interstitial tissue including groups of Leydig cells in the interstitium.

The Seminiferous Tubules

Seminiferous tubules are slender blind-ended tortuous hollow cylindrical structures. Each testis contains about five hundred seminiferous tubules. In children under the age of 3, the seminiferous tubules are characterized by a narrow or obliterated lumen. Thereafter, the lumen appears and get wider in older children. Until puberty, the wall of seminiferous appears is a low stratified epithelium containing two types of cells: spermatogonia and Sertoli cells. After puberty, the seminiferous epithelium becomes much thicker and complicated, and the lumen more conspicuous. Sertoli cells are tall transepithelial cells, whereas the sex cells are of different types that include spermatogonia, spermatocytes, spermatids and spermatozoa. Sex cell are arranged in layers giving the seminiferous epithelium a stratified appearance. The epithelium rests on a basal lamina, and the basal lamina is surrounded by myoid cells.

Fig. 1.4. H&E-stained histological sections of the testis. The one on the left is of a child; it shows low epithelium containing two types of cells. The lumen appears partially obliterated. The section on the right is of an adult testis; the epithelium is thick and contains different types of cell arranged in several clear layers. Spermatogonia are basally located overlying the basement membrane, primary spermatocytes occupy the middle regions of the epithelium and have the largest nuclei, secondary spermatocytes and spermatids occupy the luminal regions and have the smallest nuclei.

Sertoli Cells

Sertoli cells are a characteristic feature of the seminiferous epithelium. They are tall transepithelial supportive cells that extend from the basal lamina to the lumen of the seminiferous tubule. They are difficult to identify in histological sections because their lateral borders are irregular containing depressions that house the developing spermatogenic cells. The nucleus of Sertoli cells is pale irregular, indented and basally located. The cytoplasm contains several types of organelles that include rER, mitochondria, Golgi apparatus, and sER, in addition to inclusions that include secretory granules and lipid droplets.  The cytoplasm also contains unique spindle shaped filamentous structures called Charcot–Bottcher crystals. Sertoli cells have many functions that include:

1. Nourishment of sex cells

2. Production of androgen binding protein (ABP) and inhibin

3. Formation of the blood / testis barrier

4. Phagocytosis of residual bodies

5. Secretion of the tubular fluid and regulatory factors for spermatogenesis, Leydig cells and the peritubular cells. 

Fig. 1.5 The illustration on the left and the electron micrograph in the middle show Sertoli cells as tall transepithelial cells extending from the basal lamina to the luminal surface, with pale basally located nuclei and numerous cytoplasmic organelles. Sertoli cells are flanked on both side by spermatogenic cells at various stages of development. The H&E-stained section on the right shows the characteristic Charcot-Butcher body (arrow).

Tubuli Recti

The sperms formed in the seminiferous tubules are transported towards the epididymis via a series of tubular structures that include the tubuli recti, rete testis and ductuli efferentes. The tubuli recti are extensions of the seminiferous tubules. The contorted seminiferous tubules abruptly transform into straight tubules known as the tubuli recti, which are a simple columnar epithelium made of Sertoli cells alone, instead of the seminiferous epithelium that comprises spermatogonia, spermatocytes, spermatids and Sertoli cells. Tubuli recti transport the sperms into the rete testis.  

Rete Testis

Rete testis is a network of channels present within the mediastinum testis surrounded by a highly vascular connective tissue rich in myoid cells. By their contractions, myoid cells propagate the sperms towards the epididymis. Rete channels are lined by a simple cuboidal epithelium made of cells that have numerous apical microvilli, in addition to a single cilium. The microvilli increase the surface area and enhance efficiency of absorption the tubular fluid, and the cilium facilitates the percolation of the fluid within the channels,

Ductuli Efferentes

There are about twenty ducts that connect the rete testis to the epididymis; these are called efferent ductules or ductuli efferentes. The distal ends of these ducts are coiled and form part of the head of the epididymis. The epithelium of the efferent ductules is a pseudostratified epithelium that contains columnar ciliated cells alternating with cuboidal cells with microvilli, thus giving the ductular epithelium a sawtooth appearance.  

Fig. 1.6. The illustration on the left shows the different types of tubules present in the testis, and their connections to the epididymis. The H&E-stained sections in the middle show features of the rete testis, whereas the one on right shows the ductuli efferentes.

The Epididymis

Sperms carried from the testis to the epididymis are stored there until ejaculated at the climax of a sexual arousal. During storage, the sperms gain ability to move and become motile. The key factors involved in this process are calcium ions (Ca2+), bicarbonate (HCO3 −), and cyclic adenosine monophosphate (cAMP). The epididymis is a very long 4-6m long highly contorted duct with a head, body and tail. The epididymal epithelium is a high pseudostratified with stereocilia. The stereocilia are tall microvilli that are mistaken for cilia when seen under the light microscope. They greatly increase the surface area of the principal columnar cells and their absorption capabilities. They efficiently renew the epididymal fluid which holds the waste products of millions of spermatozoa.   The epithelium is made of two types of cells, the principal which are tall and basal cells. The epididymal epithelium is surrounded by a layer of connective tissue and smooth muscle. Its lumen is always full of sperms.

Fig. 1.7. The illustration on the left shows the relation of the epididymis to the testis. The histological sections in the middle and on the right are H&E-stained sections of the epididymis at low magnification (middle) and high magnification (right). The epididymal lumen is full of stored sperms and the epithelium appears pseudostratified. Numerous stereocilia cilia are clearly visible in higher magnification section on the right.

The Ductus Deferens

This is a long duct that carries sperms from the epididymis towards the urethra at a high-speed during ejaculation. It has a narrow lumen and a comparatively very thick wall consisting of an pseudostratified columnar epithelium, a connective tissue lamina propria, a tunica muscularis made of smooth muscle fibers, and a connective tissue adventitia. The tunica muscularis comprises three layers, an inner longitudinal, an outer longitudinal and in between a middle layer of circularly arranged fibers. The adventitia contains large blood vessel and bundles of nerve fibers that supply the muscularis and the mucosa.

Fig. 1.8. The illustration on the right shows the anatomical relations of the vas (ductus) deferens, whereas the H&E-stained section shows the general cross-sectional histological appearance of the vas deferens, a thick muscular wall surrounding a narrow lumen. 

Male Sex Glands

The male sex glands include a pair of seminal vesicles, a prostate and a pair of bulbourethral glands, which are also known as Cooper’s glands. The male sex glands produce most of the fluid part of the semen, which nourishes the sperms They are compound tubuloalveolar glands. Their normal functioning is maintained by testosterone, which is produced by Leydig cells in the testis. The secretions of these glands contain fructose which is needed for sperm metabolism), vitamin C which enhances sperm motility and prostaglandins which also increase sperm motility.

The Seminal Vesicles

The seminal vesicles are a pair of saccular glands located posterior to the urinary bladder. Each gland has a short duct that joins the ductus deferens at the ampulla to form the ejaculatory duct, which empties into the urethra. The fluid produced by the seminal vesicles is viscous and is rich in fructose, which provides energy for the sperms. In addition, it contains prostaglandins, which contribute to the motility and viability of sperms. It also contains proteins needed for coagulation of the semen after ejaculation. The seminal vesicles are honeycomb-shaped saccules characterized by a mucosa that is highly folded and lined by a pseudostratified, simple columnar or a simple cuboidal epithelium. Nonetheless, the epithelium is mostly simple columnar with all the nuclei basally located. The cytoplasm of the columnar cells often appears pale and the cell boundaries are clear. The epithelial cells secrete a mucoid substance rich in fructose. The folds join one another and open into a large central lumen filled with a pale-staining homogenous secretion. A smooth muscle coat surrounds the saccular glandular end-pieces. The contraction of these smooth muscle fibers expels the vesicular secretions out the gland during ejaculation. 

Fig. 1.9. The low power micrograph of an H&E-stained section of the seminal vesicle (left) shows a central lumen surrounded by a highly folded mucosa. The mucosa is surrounded by a smooth muscle layer. The higher magnification section on the right shows pale high columnar epithelial cells with basal nuclei. Thin connective tissue laminae (pink) are present in-between the epithelial membranes.

Prostate Gland

Prostate gland is the largest of the male sex glands being about the size of a walnut. It is about 4x3x2cm in dimensions and weighs about 25g in normal adult men. It is located inferior to the urinary bladder,  encircling the urethra as it emerges from the urinary bladder. Like all other glands it has two tissue components, a parenchyma and a connective tissue stroma. The parenchyma comprises about 30-50 tubuloalveolar glands, lined mostly by a simple cuboidal or simple columnar epithelium and occasionally by a pseudostratified columnar epithelium. The secretory cells often appear pale with clear cell boundaries in between. Several short ducts arise from secretory units of the parenchyma and empty into the prostatic urethra. The prostatic secretion is thin, milky colored, and alkaline. The secretion contains prostatic enzymes such as the prostatic specific enzyme (PSA) and spermine which enhance the motility of sperms. The prostate gland often contains large lamellar bodies known as corpora amylacea, which are concretions of the prostatic secretion; they increase in number with the advancement of the age of the individual.  The prostatic stroma is fibroelastic fibromuscular containing collagen type 1 fibers, elastic fibers and smooth muscle fibers, in addition to different types of connective tissue cells. The stroma consists of a capsule and an interstitium.

The prostatic capsule is a dense collagenous connective tissue investment that contains smooth muscle fibers and elastic fibers. Smooth muscle fibers are also present in the interstitium within the substance of the prostate. During ejaculation these smooth muscle fibers contract and forcefully squeeze the prostatic secretions out of the prostate into the urethra. Histologically, the prostate gland is divided into three zones, the transition zone, the central zone and the peripheral zone.

The transition zone is the innermost zone which surrounds the upper parts of the urethra; it is the smallest part of the prostate constituting only about 10% the volume of the prostate. The central zone surrounds the transition zone and makes up about 25% of the volume of prostate. The peripheral zone constitutes the main bulk (about 70%) of the prostate. The transition zone tissue tends to undergo benign (non-cancerous) growth in old age.

Fig. 1.10. Three H&E-stained sections showing the structural features of the prostate gland. The low power micrograph on the left shows the general features of the prostatic glandular unit, the high-power micrograph in the middle shows the secretory glandular epithelial cells as pale columnar cells with basal nuclei and surrounded by a loose connective containing few smooth muscle fibers. The micrograph on the right shows two corpora amylacea within the lumina of two secretory units; they are large irregular or irregular dense spherical bodies. 

The Bulbourethral Glands

The are These are also known as the bulbourethral glands; they are a pair of small compounds tubuloacinar exocrine glands, about the size of a pea, located near the base of the penis. A short duct emerges from each gland and enters the proximal end of the penile urethra. During sexual arousal, the bulbourethral glands secrete an alkaline mucus-like fluid, which neutralizes the acidity of the urine residue in the urethra, helps to neutralize the acidity of the vagina, and provides some lubrication for the tip of the penis during intercourse.

A bulbourethral gland is typically made of tubules and acini, which is why we can characterize it as a tubulo-acinar or tubulo-alveolar gland. Each gland is formed of a number of lobules that are enclosed within a fibrous capsule. Within these lobules, mucous acini are lined by simple columnar or pseudostratified epithelium. A thin layer of myoepithelial two cells surround each separate acinus. The acini open into intralobular ducts, which join each other eventually forming the central excretory duct of the gland; a simple cuboidal or columnar epithelium lines the interlobular ducts. Cowper’s glands and Bartholin glands of women are homologous. They secrete clear fluid prior to ejaculation that helps to lubricate the urethra and a small proportion of the fluid of the ejaculate.

Fig. 1.11.  The illustration on the left shows the anatomical location of the bulbourethral gland whereas the H&E-stained section shows the basophilic secretory units of the gland. The cytoplasm of the secretory cells is pale basophilic and the nuclei deep basophilic and basally located.

Semen

Semen is a whitish gray slightly alkaline mixture of sperms and the seminal fluid that is released from the peins during ejaculation during or immediately after orgasm. The seminal fluid is a mixture of the secretions from the male sex glands. It helps transport, protect and nourish sperms. Secretions from the seminal vesicles make up about 60 percent of the volume of the semen, that of the prostate constituting about 20% of the semen.  

The Penis

The penis is the male copulatory organ and is part of the male external reproductive organs. It contains the urethra which is a common outlet passage for both the reproductive and urinary systems in males. It is primarily made of erectile tissues covered by a dense irregular connective tissue investment called the tunica albuginea which in turn is covered by the skin. Erectile tissues of the penis are arranged in three columns known as the corpora cavernosa. Two of these are the proper cavernous tissues of the penis and are known as the corpora cavernosum penis, and the third is the cavernous tissue surrounding the penile urethra and is known as the corpus cavernosum urethrae.  The corpus cavernosum urethrae is frequently referred to as the corpus spongiosum.

Erectile tissues of the penis are vascular channels supplied by spiral arteries called the helicine arteries. Parasympathetic stimulation causes dilatation of the helicine arteries and filling up of the cavernous spaces with blood. Penile veins are pressed upon by the tunica albuginea thus causing further filling up of the vascular spaces and engorgement that leads to erection and hardening of the penis. The cavernous tissues comprise trabeculae and blood sinuses. Trabeculae of the cavernous tissues consist of a collagenous connective tissue rich in smooth muscle fibers. During erection the smooth muscle fibers relaxes to facilitate filling of the cavernous sinuses with blood. The cavernous sinuses are large and are lined by endothelium. A deep central artery is present in each cavernous body.

The erectile tissue of the corpus spongiosum get filled with blood during erection but does not become turgid because it is not surrounded by the tunica albuginea or any tough fibrous connective tissue investment. The urethra is lined by a pseudostratified columnar epithelium except towards its distal end where the epithelium changes into a stratified squamous epithelium. The penile urethra contains small mucous glands known as the glands of Littre.

Fig. 1.12. Showing the cavernous tissues of the penis in LS (left) and TS (right).

Fig. 1.13. H&E-stained section of the cavernous tissue of the penis showing the microscopic appearance of its sinuses and septa. 

---

 QUICK QUIZ

1. Which of the following is the site of storage os spermatozoa?

A.     Vas deference

B.    Seminal vesicle

C.    Ductuli efferentes

D.    Seminiferous tubule

E.    Epididymis

2. Interstitial cells of Leydig are characterized by which of the following?

A.    Stereocilia

B.    Crystals of Renke

C.    Charcot-Botcer’s crystals

D.    Corpora amylacea

E.    Melanin granules

3. The rete testis is connected to the epididymis by which of the following?

A.    Tubuli recti

B.    Vas deferens

C.    Ductuli efferentes

D.    Seminiferous tubules

E.    Ejaculatory ducts

4. The type of epithelium lining the epididymis is called?

A.    Simple cuboidal

B.    Stratified cuboidal

C.    Stratified squamous

D.    Simple squamous

E.    Pseudostratified

5. A tunica albuginea and numerous vascular channels are characterized by which of the following?

A.    The seminal vesicle

B.    The corpus spongiosum

C.    The prostate gland

D.    The corpus cavernosum

E.    The bulbourethral gland

CHECK ANSWERS