Anatomy and Human Biology 2214
August 18 and 24, 2009
M. Hall
MALE REPRODUCTIVE SYSTEM
Objectives: After you finish studying this lecture, you should be able to:
Recognise and name the structures of the male reproductive system
Understand the gross structure of the testis
Identify all of the cells of the seminiferous epithelium
Distinguish between spermatocytogenesis and spermiogenesis and describe the progression
of sperm through the complete process of spermatogenesis
Identify Sertoli cells and describe their main functions.
Identify Leydig cells and describe their main functions
Understand the hormonal control of spermatogenesis
Identify the ducts involved in the passage of sperm from the testes to the penis, and
describe what role each plays in the maturation of sperm
Identify the accessory sex glands and know their role in nourishing and protecting the
sperm after ejaculation
Understand the structure of the penis and how blood flow causes erection
Understand the mechanism of action of Viagra (if you understand this, then you will have
answered the previous question).
Understand the role of the sympathetic and parasympathetic nervous systems in erection
and ejaculation.
Distinguish between sperm and semen, and know the components of semen
The male reproductive system consists of the testes, genital ducts, accessory
glands and penis.
(1)
TESTES
Embryology: The testes develop in the abdomen from the indifferent gonads of the
embryo. Until the sixth week of development, the indifferent gonads, which consist of a
cortex and a medulla, are identical in both sexes. In genetic males, the medulla develops
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during the seventh and eighth weeks into a testis, and the cortex regresses. A specific gene
on the Y-chromosome, the SRY gene is thought to produce a protein, the testes
determining factor (TDF) which turns on the male genes responsible for producing the
male hormones [androgens]. If this gene is not turned on, a female results. As fetal
growth continues, the testes start to descend from their original position in the abdomen.
They pass through the inguinal canal and reach the scrotum by birth. If the testes do not
descend out of the body cavity, spermatogenesis is affected, and the male is sterile.
(Temperature of testis is 2o lower than body temp).
Functions: The testes have two interrelated functions: (1) the production of sperm
(spermatogenesis) and (2) the production of steroid hormones (steroidogenesis). These
hormones (primarily testosterone) function in the regulation of sperm development, and
the growth, development and maintenance of the accessory reproductive glands. The
steroid hormones also influence the development of secondary sex characteristics and to
some extent, sexual behavior.
Structure: Each testis is enclosed in a dense fibrous capsule, the tunica albuginea.
The anterior and lateral surfaces of the testis are covered by a closed serous sac, the tunica
vaginalis which is derived from the peritoneum. Along the posterior border of the testis,
the tunica albuginea is thickened and projects into the interior, forming the mediastinum
testis. Ducts, nerves and vessels exit and enter the testis through the mediastinum.
Numerous thin fibrous septa extend from the tunica albuginea, dividing the testis into 200300 pyramidal lobules. Each lobule contains 1-4 highly coiled seminiferous tubules,
immersed in a web of connective tissue rich in blood vessels, lymphatics, nerves and
endocrine cells (Leydig cells). The seminiferous tubules are coiled loops that empty at
both ends into a system of tubules within the mediastinum. From the mediastinum arise
12-20 tubules, the ductuli efferentes which join to the tubule system called the
epididymis. Spermatozoa and testicular fluid are produced in the seminiferous tubules,
and they pass through this system of tubules to reach the epididymis and thence onward to
the urethra.
Seminiferous tubules: The seminiferous tubules are long (30-80 cm), convoluted tubules,
and are thus seen sectioned in various planes. They consist of (1) a thin tunic of fibrous
connective tissue, (2) a basement membrane and (3) a complex stratified epithelium, the
germinal epithelium. This epithelium consists of two types of cells: (1) the supporting
cells called Sertoli cells and (2) the spermatogenic or reproductive cells in various stages
of differentiation. The process by which the germ cells proliferate and transform into
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spermatozoa is called spermatogenesis. Spermatogenesis can be divided into three
phases:
(1)
Spermatocytogenesis - during which spermatogonia, (diploid, 2N) situated next to
the basal lamina, divide mitotically, producing cells that eventually give rise to primary
spermatocytes (diploid, 4N)
(2)
Meiosis - during which the 46 chromosomes (diploid, 4N) of a primary
spermatocyte undergo two successive divisions, resulting in four cells called spermatids,
each with only 23 chromosomes (haploid, N).
(3)
Spermiogenesis - during which the haploid spermatids go through a series of
differentiations to produce haploid spermatozoa.
All three phases of spermatogenesis take place within the seminiferous tubules,
from the spermatogonia at the basement membrane to the mature spermatids at the lumen
of the tubule. (Note: Although the spermatids are morphologically differentiated, they are
not yet motile, a process which occurs in the epididymis).
Identification of the various stages of development can be difficult, although if you
remember that cells move from the basement membrane of the seminiferous tubule to the
lumen with increasing differentiation, the task becomes easier.
Spermatogonia are large, diploid germ cells, situated in the basal compartment of
the seminiferous tubules. Subsequent to puberty, these cells are induced by testosterone to
enter the cell cycle.
Primary spermatocytes are found just above the spermatogonia and are quite
numerous. They are large cells with a more darkly staining nucleus, often seen with
dividing chromosomes. As they migrate between the Sertoli cells, they form zonula
occludens with these cells, thus maintaining the integrity of the blood-testis barrier.
Secondary spermatocytes are not often seen as they divide soon after formation,
each giving rise to two spermatids.
Spermatids are seen in two stages--early and late stage. Early spermatids are
round and cellular. They are smaller than spermatocytes with small nuclei containing
condensed chromatin, and they usually lie close to the lumen. Late spermatids are easily
recognized as they have begun to take the shape of spermatozoa. They are closely
associated with the Sertoli cells, often with the residual body still attached.
The process of spermiogenesis, or maturation of the spermatids to spermatozoa,
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occurs while the spermatids are attached to the Sertoli cells. Mature spermatozoa are
released into the lumen of the seminiferous tubule and undergo further maturation to
become motile and hence fertile, as they pass through the epididymis. In humans, it takes
about 64 days for a spermatogonium to complete the process of spermatogenesis,
(spermatogonium to spermatozoan) and about 12 days for the spermatozoa to pass through
the epididymis.
Spermatogenesis occurs in a wavelike fashion. Thus different regions of the same
seminiferous tubule exhibit different phases of spermatogenesis. You may see tubules that
contain late spermatids, while other regions contain spermatozoa.
Thus the three phases of spermatogenesis can be represented as follows:
spermatocytogenesis
meiosis
_______
spermatogonia (2N)-primary spermatocytes(4N)-secondary spermatocytes(2N)-spermatids(N)
spermiogenesis
spermatids(N)--spermatozoa(N).
Sertoli cells: The Sertoli cells are the supportive cells of the seminiferous tubules. They
are tall columnar cells extending from the basement membrane to the lumen of the tubule.
Each Sertoli cell surrounds its neighboring spermatogenic cells and fills up all the spaces
between them. Specialized tight junctions (zonula occludens) are formed between
adjacent Sertoli cells, thus producing a blood-testis barrier, which maintains a
microenvironment for the spermatogenic cells to proceed through meiosis and
differentiation to spermatozoa. The young spermatocytes must pass through the junctional
complexes in order to reach the lumen.
Sertoli cells have at least four main functions in the development and
differentiation of the spermatogenic cells.
1.
Support, protection and nutritional regulation of the developing spermatozoa.
During spermatogenesis, the cells are constantly surrounded and supported by the Sertoli
cells. The presence of tight junctions at the base of these cells isolates the developing
spermatids from the blood supply and protects them from immunologic attack. These
junctions also ensure that the spermatogenic cells depend on the Sertoli cells to mediate the
exchange of nutrients.
2.
Phagocytosis. The Sertoli cells phagocytize the residual bodies released from the
spermatids during spermiogenesis.
3.
Secretion. Sertoli cells continuously secrete a fluid (testicular fluid) into the lumen
of the seminiferous tubule that nourishes and facilitates the transport of sperm to the genital
ducts.
4.
Production of Androgen-binding protein (ABP). which binds testosterone, thus
concentrating this hormone in the seminiferous epithelium where it is essential for
spermatogenesis. They also secrete a peptide called inhibin, which suppresses FSH
synthesis by the anterior pituitary.
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Sertoli cells
Leydig cells
Leydig (interstitial) cells: Leydig cells are large and ovoid in shape and are situated in the
connective tissue between the tubules. They are endocrine cells and thus are associated
with blood vessels. These cells produce the male hormone testosterone, an adequate
supply of which is necessary for the growth and secretory activity of the accessory sex
glands, i.e. seminal vesicles, prostate and bulbourethral glands. A high local level of
testosterone within the seminiferous tubules is also necessary for sperm production.
Testosterone is also responsible for the development and maintenance of secondary sex
characteristics, such as facial and pubic hair, low voice, muscularity, behavior, libido, etc.
Testosterone levels are quite low from before birth until puberty, when they increase in
response to the stimulus of luteinizing hormone (LH) from the pituitary. (Coincidentally,
this increase in testosterone levels appears to be a signal for the migration of the male brain
down to the penis, where it resides for the next 40 or 50 years).
Hormonal control of spermatogenesis: Both the endocrine function (production of
testosterone) and the exocrine function (spermatogenesis) of the testes are strongly
regulated by the pituitary gonadotrophic hormones, luteinizing hormone (LH) and follicle
stimulating hormone (FSH). The endocrine function of the testis primarily resides in the
Leydig cells, which synthesize and secrete the principal androgen, testosterone. As the
testosterone leaves the Leydig cells, it may pass into the blood, or it may pass through the
peritubular tissue, and enter the seminiferous tubules. High local levels of testosterone
within the testis (greater than 200 times the circulating levels) are necessary for the
proliferation and differentiation of the spermatogenic cells within the seminiferous
epithelium. The lower circulating level of testosterone influences (1) the growth and
maintenance of secondary sexual characteristics (such as growth of beard, distribution of
hair and low-pitched voice): (2) the growth and maintenance of the accessory sex glands
(seminal vesicles, prostate and bulbourethral), genital duct system and external genitalia:
(3) anabolic and general metabolic processes (such as skeletal growth, muscle growth, fat
distribution) and (4) behavior, including libido, channel surfing and watching the West
Coast Eagles.
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The anterior pituitary produces two principal hormones involved in this process:
luteinizing hormone (LH) and follicle cell stimulating hormone (FSH). LH is released
by the pituitary in response to low serum testosterone levels and stimulates Leydig cells to
produce testosterone from cholesterol. Because blood testosterone levels are not sufficient
to initiate and maintain spermatogenesis, FSH, also from the anterior pituitary, stimulates
the Sertoli cells to synthesize and release Androgen binding protein (ABP). The function
of this protein is to bind testosterone, thereby establishing a high local concentration (200x)
of this hormone in the seminiferous tubules and the initial portion of the duct system. This
elevated level is required to sustain spermatogenesis.
A second important substance produced by the Sertoli is Inhibin, which functions
in the regulation of the FSH levels and thus aids in regulating the number of cells entering
spermatogenesis.
2).
GENITAL DUCT SYSTEM
After production in the seminiferous tubules, the spermatozoa are transported
through a series of ducts and stored until they are expelled through the penis during
ejaculation. Feeding into this extended tubular system are the accessory sex glands: the
seminal vesicles, prostate gland and bulbourethral gland.
The seminiferous tubules connect with a series of channels within the dense
connective tissue of the mediastinum, called the rete testis. At the superior end of the
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mediastinum, 12 to 20 efferent ducts leave the testis and coil into a mass to form the head
of the epididymis. These efferent ducts are lined with a pseudostratified columnar
epithelium, consisting of alternating groups of tall columnar and cuboidal cells, both of
which may be ciliated or non-ciliated. The differing cell height gives this tubule a wavy
appearance. The ciliated cells aid in the transport of sperm and fluids, while the nonciliated cells possess numerous microvilli and have an absorptive function (most of the
fluids produced within the seminiferous tubules are absorbed in the efferent ducts and the
epididymis).
The efferent ducts join to form a single highly convoluted ductus epididymis, which is
about 6 meters long. It consists of a head, a body and a tail. The ductus epididymis is
lined with a pseudostratified columnar epithelium consisting of two main cell types -small basal cells lying near the basement membrane, and tall columnar cells (principal
cells) whose surfaces are covered with non-motile stereocilia (These are not cilia at all but
long microvilli). Most of the fluid that is not absorbed by the efferent ducts is absorbed in
the epididymis. The tubule of the epididymis is surrounded by a thin coat of smooth
muscle whose peristaltic contractions help to move sperm along the duct. The tail of the
epididymis is the principal site of sperm storage. The epydidymus also provides the
essential environment and some of the molecular products required for maturation of the
sperm. This maturation, like their earlier differentiation, is androgen dependent. It is within
the epididymis that spermatozoa become motile and hence fertile. The head and most of
the body of the epididymis contain only a thin layer of smooth muscle, which undergoes
rhythmic peristaltic contractions to move the sperm along the duct. The tail contains three
distinct muscle layers, similar to that seen in the vas deferens. Intense contractions of these
three muscle layers, after appropriate neural stimulation, force the sperm into the vas
deferens during ejaculation.
The vas deferens begins as a direct continuation of the ductus epididymis and
eventually empties into the prostatic urethra. The epithelium of the vas deferens is
pseudostratified and stereociliated along most of its length. The wall of the vas is
composed of three layers of smooth muscle, an internal longitudinal, a middle circular, and
an outer longitudinal layer, as seen in the tail of the epididymis. An extensive myenteric
nerve plexus is present in these muscle layers. Sympathetic nervous stimulation of the
smooth muscle surrounding the vas deferens causes powerful contractions that expel the
spermatozoa at ejaculation. The adventitia of the vas deferens blends with the tissues of
the spermatic cord through which the vascular and neural supply to the testes are carried.
Vasectomy (male sterilization) is simply performed by cutting both of the vas deferens, and
tying the cut ends. This very effectively prevents sperm from being added to all of the
other components of semen during ejaculation.
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3).
ACCESSORY SEX GLANDS
Feeding into the duct system which conducts sperm from the testes to the urethra
are three accessory sex glands -- the seminal vesicles, prostate and bulbourethral
glands.
Each seminal vesicle is a long, convoluted tubular structure which opens into the
vas deferens just as it enters the prostate gland. (As it is a highly convoluted tube, it is seen
in different orientations on sectioning). The pseudostratified epithelium consists of tall or
short columnar cells and basal cells ,arranged irregularly along the basement membrane.
These cells produce a thick secretion, rich in fructose, flavins, vitamin C and
prostaglandins. This secretion, which is stored in the seminal vesicles, is eliminated
during ejaculation by the contraction of its smooth muscle coat, and provides nutrient
material for the spermatozoa. The activity of the gland is controlled by the level of
testosterone in the blood and thus varies with the age of the individual.
Cells of the seminal vesicle
Structure of Prostate gland
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The prostate gland is a collection of 30-50 branched tubuloalveolar glands whose ducts
converge into about 20 terminal ducts that open into that part of the urethra called the
prostatic urethra. The prostate produces prostatic fluid and stores it in its interior for
expulsion during ejaculation. This fluid is rich in citric acid, acid phosphatase,
fibrinolysin and proteolytic enzymes that function in liquefaction of the semen after
ejaculation. This allows the sperm to start their journey to the Fallopian tubule to fertilize
the egg. The secretion of the gland is controlled by the level of testosterone. The gland is
surrounded by a fibroelastic capsule, rich in smooth muscle. Contraction of this smooth
muscle, as well as of smooth muscle in the mucosa of the glandular epithelium, expels the
prostatic fluid during ejaculation. The cells of the prostatic epithelium vary from simple
cuboidal or columnar to pseudostratified columnar. A characteristic feature of the prostate
is the presence of prostatic concretions (corpora amylacea) which are glycoprotein-rich
bodies that are often calcified. Their number increases with age.
As men age, the stroma and parenchyma begin to hypertrophy, a condition known
as benign prostatic hypertrophy. The enlarged prostate partly constricts the urethra,
resulting in difficulties with urination. Adenocarcinoma of the prostate is a common form
of cancer in men, which affects 30% of the male population over the age of 75. It is a slow
growing but highly metastatic form of cancer. However, a simple blood test can detect the
prostate specific antigen (PSA) which allows early detection of this condition.
The paired bulbourethral glands open into the urethra at the base of the penis.
During arousal, they produce a clear, alkaline, viscous secretion that coats the lining of the
urethra and acts as a lubricant for the spermatozoa as they travel through the urethra. This
secretion also neutralizes residual urine in the urethra, the acidity of which would be
harmful to the spermatozoa.
4).
PENIS
The penis is a structure which, when erect, can conduct sperm into the vagina. This
organ consists of three cylindrical masses of erectile tissue - two corpora cavernosa which
lie above a single corpus spongiosum, The urethra passes through the corpus
spongiosum. A dense fibrous coat, the tunica albuginea surrounds each of the three
bodies, and all three of these erectile bodies are surrounded by a layer of dense connective
tissue and covered with thin skin and a stratified squamous epithelium.
The erectile structures consist of numerous interconnected cavernous spaces created
by a network of fine trabeculae that contain fibroelastic tissue and smooth muscle. The
spaces are lined with typical vascular endothelium. The penis becomes erect when the
trabecular spaces are distended with blood. Blood enters the cavernous spaces from the
helicine arteries. Real or imaginary erotic stimuli evoke parasympathetic activity that
dilates the helicine arteries resulting in an increased blood flow through them, thus causing
the cavernous sinuses to fill with blood and the penis to become erect. Back-flow through
peripheral veins is obstructed by compression against the tunica albuginea, further
contributing to maintenance of the erection. Sympathetic stimulation of the smooth
muscle of the arteries at the end of ejaculation decreases arterial blood flow and increases
venous drainage, resulting in detumescence and return to the flaccid state.
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Structure of penis
Blood flow to erectile tissue
Viagra: The physiologic mechanism of erection of the penis involves the production of
nitric oxide (NO) by NO synthase during sexual stimulation. Parasympathetic impulses
triggered during sexual arousal cause the local release of NO, which activates the enzyme
guanylate cyclase in the smooth muscle cells surrounding the arteries leading to the
trabecular meshwork and increasing the levels of cGMP. Increased cGMP and decreased
calcium causes relaxation of the smooth muscle of the arteries feeding into the penis and
probably of smooth muscle in the trabeculae of the corpus cavernosum, increasing the flow
of blood into the penis, resulting in erection. After orgasm, the enzyme phosphodiesterase type 5, (PDE 5) causes the hydrolysis of cGMP, constriction of the
arteries and decrease of blood flow into the erectile tissue, and thus detumescence. Viagra
acts by inhibiting PDE 5. When sexual stimulation causes local release of NO and the
production of cGMP, inhibition of -PDE 5 by Viagra causes increased and sustained
levels of cGMP, resulting in continued smooth muscle relaxation and inflow of blood to the
corpus cavernosum. This can result in the maintenance of erection for 2-4 hours. Viagra is
highly selective for PDE 5, which is important since a very similar enzyme, PDE 3,
is involved in cardiac contractility. The only known -PDE that is also affected by Viagra
is PDE 6, which is present in the retina, probably resulting in the increased blue color
sensitivity reported by a small percentage of Viagra users. (I bet you never thought that sex
could be this dull!!).
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Mechanism of action of Viagra
Semen: In addition to spermatozoa, the semen contains contributions from the accessory
sex glands. Ejaculation is initiated by sympathetic stimulation of the smooth muscle
bundles associated with the genital ducts and accessory sex glands. Contraction of these
muscles forces the secretory products from the glands and propels the sperm and fluids
along the duct system. At ejaculation, the different components of the semen usually
follow one another in a definite sequence. 1. During arousal, mucous-like fluids are
released from the bulbourethral glands and act as a lubricant. 2. As ejaculation begins, the
acid phosphatase and citric acid-rich secretions of the prostate gland are released. 3. The
spermatozoa then follow these secretions. 4. The seminal vesicles then add the final
component, a substance rich in fructose, which nourishes the sperm while in the vagina.
The volume of the ejaculate in humans is 2-6 ml, 95% of which is contributed by
the accessory glands. The average sperm density is about 100 million/ml -- compare this
with one egg released each month in the female. Only a few hundred sperm reach the
ampulla region of the oviduct, where fertilization occurs.
A little known fact...
The first testicular guard (Box) was used in cricket in 1874 and the
first helmet was used in 1974.
It took 100 years for men to realize that the brain is also important!
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