› TESTES
smooth ER (SER) and mitochondria
 surrounded by a dense connective tissue capsule, the
tunica albuginea: thickens on the posterior side to
form the mediastinum testis.
 septa penetrate the organ and divide it into about 250
pyramidal compartments or testicular lobules.
Each lobule contains:
1. sparse connective tissue
2. endocrine interstitial cells (or Leydig cells) secreting
testosterone
3. one to four highly convoluted seminiferous tubules
 During migration from the abdominal cavity, each
testis carries with it a serous sac, the tunica vaginalis,
derived from the peritoneum.
 tunica vaginalis: consists of an outer parietal layer
lining the scrotum and an inner visceral layer,
covering the tunica albuginea on the anterior and
lateral sides of the testis
 process of sperm formation cannot occur at the core
body temperature of 37°C.
 34°C: A permissive temperature maintained in the
scrotal sac by various mechanisms
 Each testicular artery is surrounded by a rich
pampiniform venous plexus containing cooler blood
from the testis, which draws heat from the arterial
blood by a countercurrent heat-exchange system
 Evaporation of sweat from the scrotum also
contributes to heat loss.
 Relaxation or contraction of the thin dartos muscle
of the scrotum and the cremaster muscles of the
spermatic cords move the testes away from or closer
to the body, respectively
 Ductus deferens: located along the anterior and
superior sides of the bladder as a result of the testes
descending into the scrotum from the abdominal
cavity during fetal development.
Interstitial Tissue
 between the seminiferous tubules
 consists of:
sparse connective tissue containing fibroblasts,
lymphatics, and blood vessels including fenestrated
capillaries
 During puberty interstitial cells, or Leydig cells,
develop as large round or polygonal cells with central
nuclei and eosinophilic cytoplasm rich in small lipid
droplets.
 Testosterone is synthesized by enzymes present in the
 Testosterone secretion by interstitial cells is triggered
by the pituitary gonadotropin, luteinizing hormone
(LH), which is also called interstitial cell-
stimulating hormone (ICSH).
 Testosterone synthesis thus begins at puberty, when
the hypothalamus begins producing gonadotropin-
releasing hormone
 fetal interstitial cells are very active during the third
and fourth months (3-4) of pregnancy,
 become quiescent cells resembling fibroblasts until
puberty
Seminiferous Tubules
 Sperm are produced in the seminiferous tubules at a
rate of about 2 × 108 per day in the young adult
 Each testis has from 250 to 1000 tubules in its
lobules.
 each tubule measures 150-250 μm in diameter and 30-
70 cm in length.
 combined length of the tubules of one testis totals
about 250 m
 Each tubule is actually a loop linked by a very short,
narrower segment, the straight tubule, to the rete
testis (a labyrinth of epithelium-lined channels
embedded in the mediastinum testis)
 About 10-20 efferent ductules connect the rete testis
to the head of the epididymis.
 lined with a complex, specialized stratified
epithelium called germinal or spermatogenic
epithelium
 basement membrane of this epithelium is covered by
fibrous connective tissue, with an innermost layer
containing flattened, smooth muscle-like myoid cells:
allow weak contractions of the tubule.
The germinal epithelium consists of two types of cells:
■ Large nondividing Sertoli cells which physically and
metabolically support developing sperm cell precursors
■ Dividing cells of the spermatogenic lineage
 spermatogenic lineage: comprising four or more
concentric layers of cells in the germinal epithelium,
develop from progenitor cells to fully formed sperm
cells over a period of approximately 10 weeks.
 Spermatogenesis: the first part of sperm production
involves mainly mitosis and meiosis and is followed
by spermiogenesis
 spermiogenesis: final differentiation process
occurring in the haploid male germ cells
  Most spermatocytes seen in sections of testis are in
this phase of meiosis.
 largest cells of the spermatogenic lineage
 characterized by the presence of partially condensed
chromosomes in various stages of synapsis and
recombination
 Homologous chromosomes separate in the first
meiotic division, which produces smaller cells called
secondary spermatocytes with only 23
chromosomes (22 + X or 22 + Y), but each still
consists of two chromatids so the amount of DNA is
2N

Spermatogenesis
 begins at puberty with proliferation of stem and
progenitor cells called spermatogonia (small round
cells about 12 μm in diameter.)
 occupy a basal niche in the epithelial wall of the
tubules, next to the basement membrane and closely
associated with Sertoli cell surfaces
 Spermatogonia with dark, ovoid nuclei act as stem
cells, dividing infrequently and giving rise both to
new stem cells and to cells with more pale-staining,
ovoid nuclei that divide more rapidly as transit
amplifying (progenitor) Cells.
 type A spermatogonia each undergo several unique
clonal divisions that leave most of the cells
interconnected as a syncytium.
 These become type B spermatogonia, which have
more spherical and pale nuclei.
 Each type B spermatogonium then undergoes a final
mitotic division to produce two cells that grow in size
and become primary spermatocytes
 Primary spermatocytes replicate their DNA, so each
chromosome consists of duplicate chromatids, and
enter meiosis, during which homologous
chromosomes come together in synapsis, DNA
recombination occurs, and two rapid cell divisions
produce haploid cells
Primary spermatocyte

 has 46 (44 + XY) chromosomes, the diploid number,

and a DNA content of 4N. (The letter N denotes
either the haploid number of chromosomes, 23 in
humans, or the amount of DNA in this set.)
 these cells enter the first meiotic prophase that lasts
about 3 weeks
 The Clonal Nature of Male Germ Cells

 stem cells produced by mitotic divisions of

spermatogonia remain as separate cells.
 transit amplifying progenitor cells, have incomplete
cytokinesis after telophase and the cells remain
attached to one another by intercellular bridges of
cytoplasm
 allow free cytoplasmic communication among
the cells during their remaining mitotic and
meiotic divisions
 clones of approximately a hundred cells may remain
 Secondary spermatocytes are rare in testis sections
linked through meiosis.
because they are very short-lived cells that remain in
 complete significance of this spermatogenic
interphase only briefly and quickly undergo the
syncytium is not clear, but the cytoplasmic bridges
second meiotic division.
allow the haploid cells to be supplied with products of
 Division of each secondary spermatocyte: separates
the complete diploid genome, including proteins and
the chromatids of each chromosome and produces two
RNA encoded by genes on the X or Y chromosome
haploid cells called spermatids each of which
missing in their haploid nuclei.
contains 23 chromosomes
 germ cells finally become separated from one another
 Because no S phase (DNA replication) occurs
during differentiation
between the first and second meiotic divisions, the
 cellular events and changes between the final mitoses
amount of DNA per cell is reduced by half when the
of spermatogonia and the formation of spermatids
chromatids separate and the cells formed are haploid
take about 2 months
(1N).
 spermatogenic cells are not randomly distributed in
 With fertilization, a haploid ovum and sperm
the spermatogenic epithelium.
produced by meiosis unite and the normal diploid
 Cells at different stages of development are typically
chromosome number is restored.
grouped together along the tubule
 with the intercellular bridges helping to coordinate
their divisions and differentiation.

Spermiogenesis
 the final phase of sperm production, is the
temperature-sensitive process by which spermatids
differentiate into spermatozoa
 No cell division occurs during this process
 the cells involved remain associated with Sertoli
cells.
 haploid spermatids are small (7-8 μm in diameter)
cells near the lumen of the seminiferous tubules

Spermiogenesis includes formation of the:

1. acrosome
2. condensation and elongation of the nucleus
3. development of the flagellum
4. loss of much of the cytoplasm

Spermiogenesis is commonly divided into four phases:

 Golgi phase
 Cap phase
 Acrosome phase
 Maturation phase

Golgi Phase
cytoplasm contains:
 prominent Golgi apparatus near the nucleus,
mitochondria
 paired centrioles
 free ribosomes.
 Small proacrosomal vesicles from the Golgi
apparatus coalesce as a single membrane-limited
acrosomal cap close to one end of the nucleus
 Centrioles: migrate to a position farthest from the
acrosomal cap and one acts as a basal body,
organizing the axoneme of the flagellum which is
structurally and functionally similar to that of a
cilium.
Cap phase
 acrosomal cap spreads over about half of the
condensing nucleus
 Acrosome: specialized type of lysosome containing
hydrolytic enzymes, mainly
1. hyaluronidase
2. trypsin-like protease called acrosin
 acrosomal membrane fuses with the sperm’s
plasma membrane.
 They dissociate cells of the corona radiata and digest
the zona pellucida
 This process, the acrosomal reaction, is one of the
first steps in fertilization.
Acrosome Phase
 the head of the developing sperm, containing the
acrosome and the condensing nucleus, remains
embedded in the Sertoli cell
 growing axoneme extends into the lumen of the tubule
 Nuclei become more elongated and very highly
condensed, with the histones of nucleosomes:
replaced by small basic peptides called protamines
 Flagellum growth continues distally in the tail
 mitochondria aggregate around it proximally to form a
thickened middle piece where the ATP for flagellar
movements is generated
Maturation phase
 unneeded cytoplasm is shed as a residual body from
each spermatozoon
 remaining intercellular bridges are lost.
 Fully formed, but not yet functional or mobile, sperm
are released into the lumen of the seminiferous tubule.
Sertoli Cells
 first demonstrated their physiologic significance, are
tall “columnar” epithelial cells
 nourish the spermatogenic cells and divide the
seminiferous tubules into two (basal and adluminal)
compartments.
 All cells of the spermatogenic lineage are closely
associated with the extended surfaces of Sertoli cells
and depend on them for metabolic and physical
support.
 adhere to the basal lamina and their apical ends extend
to the lumen
 Sertoli cells surrounding the spermatogenic cells are
very poorly defined
 Each Sertoli cell supports 30-50 developing germ
cells
seen to contain:
 abundant SER
 some rough ER
 Well developed Golgi complexes
 numerous mitochondria
 lysosomes
 nuclei are typically ovoid or triangular, euchromatic,
and have a prominent nucleolus,
 features that allow Sertoli cells to be distinguished
from the neighboring germ cells
 elaborate tight occluding junctions between their
basolateral membranes, which form a blood testis
barrier within the seminiferous epithelium
 tightest blood-tissue barrier in mammals, this
physical barrier is one part of a system preventing
autoimmune attacks against the unique spermatogenic
cells
 Spermatogonia lie in a basal compartment of the
tubule, below the tight junctions and not sealed off
from the vascularized interstitial tissue containing
lymphocytes and other immune cells.
 Newly formed primary spermatocytes: temporarily
disassemble the adhesion molecules of the local
occluding junctions and move into the tubule’s
adluminal compartment while still adhering to Sertoli
cells
 all spermatocytes and spermatids lie within
invaginations of the Sertoli cells surfaces.
 Adluminal migration occurs without compromising
the blood-testis barrier
 germ cells remain linked by intercellular bridges.
 Sertoli cells are also connected and coupled ionically
by gap junctions, which may help regulate the
transient changes in the occluding junctions and
synchronize activities in the spermatogenic cells.
 Sertoli cells have three general functions:
1. Support, protection, and nutrition of the developing
spermatogenic cells:
 spermatocytes, spermatids, and developing sperm are
isolated from plasma proteins and nutrients by the
blood-testis barrier, they depend on Sertoli cells for
production or transport into the lumen of metabolites
and nutritive factors such as the iron-transport
protein transferrin
 Sertoli cells supply many plasma factors needed for
cell growth and differentiation.

2. Exocrine and endocrine secretion:
 continuously release into the seminiferous tubules
water that carries new sperm out of the testis
 Production of nutrients and androgen-binding
protein (ABP)which concentrates testosterone to a
level required for spermiogenesis, is promoted by
follicle-stimulating hormone (FSH)
endocrine cells:
1. Secrete glycoprotein inhibin, which feeds back on the
anterior pituitary gland to suppress FSH synthesis and
release
2. fetus Sertoli cells also secrete glycoprotein called
müllerian-inhibiting substance (MIS) causes regression
of the embryonic müllerian (paramesonephric) ducts
3. Phagocytosis:
 During spermiogenesis, excess cytoplasm shed as
residual bodies is phagocytosed and digested by
Sertoli cell lysosomes.
 No proteins from sperm normally pass back across the
blood-testis barrier.
INTRATESTICULAR DUCTS
 straight tubules (or tubuli recti)
 rete testis
 efferent ductules
 carry spermatozoa and liquid from the seminiferous
tubules to the duct of the epididymis.
 loops of seminiferous tubules join the rete testis by the
short straight tubules, which are lined initially only by
Sertoli cells
 straight tubules (or tubuli recti) empty into the rete
testis: an interconnected network of channels lined
with cuboidal epithelium and supported by
connective tissue of the mediastinum
 rete testis: drains into about 20 efferent ductules
lined by an unusual epithelium in which groups of
nonciliated cuboidal cells alternate with groups of
taller ciliated cells and give the tissue a characteristic
scalloped appearance Efferent Ductules.
 nonciliated cells of efferent ductule absorb some of
the fluid secreted by the Sertoli cells of seminiferous
tubules.
 absorption and the ciliary activity create a fluid flow,
which carries sperm passively out of the testis toward
the epididymis.
 A thin layer of circularly oriented smooth muscle
cells in the walls of efferent ductules aids the
movement of sperm into the duct of the epididymis.
EXCRETORY GENITAL DUCTS
excretory genital ducts are those of the:
1. Epididymis
2. ductus (or vas) deferens
3. urethra.
Epididymis
 long, highly coiled duct of the epididymis, surrounded
by connective tissue lies in the scrotum along the
superior and posterior sides of each testis
 6 m in length, the epididymis includes:
1. head region: where the efferent ductules enter
3. body: where sperm cells undergo further subtle
modifications
4. tail where sperm are stored until ejaculation.
 epididymal duct: is lined with pseudostratified
columnar epithelium consisting of columnar
principal cells (long stereocilia and small round stem
cells)
 principal cells: remove most of the water and residual
bodies entering the epididymis with the sperm and
secrete various products, greatly changing the fluid
in which sperm are suspended (exocytosis)
 these epithelial cells release abundant 25-300-nm-
diameter exosomes and other vesicles from
multivesicular bodies and by apocrine secretion.
 contain many different proteins, glycoproteins,
glycolipids, and lipids, their composition varying
along the epididymis.
 Passage of sperm through the duct of the epididymis
normally takes 2-4 weeks
 during which time the spermatozoa cell membranes
bind and integrate many components secreted by the
principal cells and released from their exosomes
In general, changes within spermatozoa while passing
through the epididymis include:
■ development of competence for forward motility,
■ final modifications within the acrosome, and
■ reorganization of the cell membrane surrounding the
sperm head, including the addition of cholesterol and other
“decapacitation factors”, which block the acrosomal
reaction, a key event in fertilization.

 The fertilizing ability of spermatozoa is inhibited until

their cell membranes are modified again as part of the
capacitation process, which occurs in the female
reproductive tract.

 epididymal duct is surrounded by a thin, circular

layer of smooth muscle cells, supplemented in the tail
region with the addition of inner and outer
longitudinal layers.
 tail region: which is continuous with the ductus
deferens.

Ductus or Vas Deferens

 Each ductus (or vas) deferens, a long straight tube
with a thick, muscular wall and small lumen,
 empties into prostatic urethra
 Leaves the scrotum
 mucosa is slightly folded longitudinally
 lamina propria: contains many elastic fibers
epithelial lining is pseudostratified with some cells
having sparse stereocilia
very thick muscularis consists of:
 longitudinal inner layer
 Longitudinal outer layers
 middle circular layer
 muscles produce strong peristaltic contractions during
ejaculation, which rapidly move sperm along this duct
from the epididymis
 forms part of the spermatic cord, which also includes
the testicular artery, the pampiniform plexus, and
nerves
 each ductus passes over the urinary bladder where
it enlarges as an ampulla: where the epithelium is
thicker and more extensively folded
 Within the prostate gland:the ends of the two
ampullae merge with the ducts of the two seminal
vesicles
 joining these ducts to form the ejaculatory ducts
which open into the prostatic urethra.
(a) The long, coiled duct of the epididymis (DE), where
sperm undergo maturation and short-term storage, is
enclosed by connective tissue with many blood vessels (V)
and covered by a capsule and the tunica vaginalis (TV).
The duct is lined by a pseudostratified columnar
epithelium with long stereocilia (arrows). (X140; H&E)
(b) The columnar epithelium of the epididymal duct is
surrounded by a thin circular layer of smooth muscle
(SM) cells and its lumen contains sperm (S). The smooth
muscle becomes thicker and a longitudinal layer develops
in the body and tail of the epididymis. (X400; H&E)
(c) The inset photo shows the epithelium with tall principal
cells (P) with stereocilia and fewer small basal stem cells
(B). Intraepithelial lymphocytes are also commonly seen in
the epididymal duct. (X500; H&E)
ACCESSORY GLANDS
produce secretions, which become mixed with sperm
during ejaculation to produce semen
The accessory genital glands are the:
 seminal vesicles (or glands)
 prostate gland
 bulbourethral glands
Seminal Vesicles
consist of highly tortuous tubes
each about 15-cm long
enclosed by a connective tissue capsule.

 unusual mucosa of the tube displays a great number

of thin, complex folds, which fill much of the lumen
folds are lined with simple or pseudostratified
columnar epithelial cells rich in secretory granules.
 lamina propria: contains elastic fibers and is
smooth muscle with inner circular and outer
longitudinal layers, which empty the gland during
ejaculation.
 are exocrine glands in which production of their
viscid, yellowish secretion depends on testosterone.
 Fluid from seminal vesicles typically makes up about
70% of the ejaculate and its components
 include the following:

 Fructose, a major energy source for sperm, as well as

inositol, citrate, and other metabolites
■ Prostaglandins, which stimulate activity in the female
reproductive tract
■ Fibrinogen, which allows semen to coagulate after
ejaculation

prostate gland
 a dense organ surrounding the urethra
 below the bladder.
 approximately 2 cm × 3 cm × 4 cm in size weighs
 about 20 g.
 consists of a collection of 30-50 tubuloacinar glands
embedded in a dense fibromuscular stroma in which
smooth muscle contracts at ejaculation
 Ducts from individual glands may converge but all
empty directly into the prostatic urethra
the glands are arranged in three major zones
around the urethra:
1. transition zone
occupies only about 5% of the prostate volume
surrounds the superior portion of the urethra, contains the
periurethral mucosal glands
2. central zone comprises 25% of the gland’s tissue
contains the periurethral submucosal glands with longer
ducts.
3. peripheral zone
70% of the organ’s tissue
contains the prostate’s main glands with still longer ducts
 tubuloacinar glands of the prostate are lined by
simple or pseudostratified columnar epithelium
 -produce a fluid that contains a complex mixture of
exosomes, various glycoproteins, enzymes, and small
molecules such as prostaglandins
 One product of the prostate is prostate-specific
antigen (PSA), a 34-kDa serine protease, which
helps liquefy coagulated semen for the slow release
of sperm after ejaculation.
 Small amounts of PSA also leak normally into the
prostatic vasculature
 elevated levels of circulating PSA indicate abnormal
glandular mucosa typically due to prostatic
carcinoma or inflammation
 corpora amylacea: Small spherical concretions, up
to 2 mm in diameter
 often partially calcified are normally present in the
lumens of many prostatic tubuloacinar glands
(containing primarily deposited glycoproteins and
keratan sulfate, may become more numerous with
age but seem to have no physiologic clinical
significance.
 The prostate is surrounded by a fibroelastic capsule,
from which septa extend and divide the gland into
indistinct lobes.
 prostate’s structure and function depend on the level
of testosterone

Bulbourethral Glands
 (or Cowper glands), 3-5 mm in diameter
 located in the urogenital diaphragm
 empty into the proximal part of the penile urethra
 has several lobules
 with tubuloacinar secretory units surrounded by
smooth muscle cells
 lined by a mucus-secreting simple columnar
epithelium
 testosterone-dependent
 Erection: the bulbourethral glands, as well as
numerous, very small, and similar urethral glands
along the penile urethra, release a clear mucus-like
secretion, which coats and lubricates the urethra in
preparation for the imminent passage of sperm.
› PENIS
 consists of three cylindrical masses of erectile tissue,
plus the penile urethra
 Two of the erectile masses—
1. corpora cavernosa—are dorsal
2. corpus spongiosum- ventral, surrounds the urethra.
 At its end the corpus spongiosum expands, forming
the glans
 lined with pseudostratified columnar epithelium.
glans: becomes stratified squamous epithelium
continuous with that of the thin epidermis covering
the glans surface.
 Small mucus-secreting urethral glands are found
along the length of the penile urethra
 prepuce or foreskin: a retractable fold of thin skin
with sebaceous glands on the internal surface.
 corpora cavernosa are each surrounded by a dense
fibroelastic layer, the tunica albuginea
 All three erectile tissues consist of many venous
cavernous spaces lined with endothelium
 Separated by trabeculae with smooth muscle and
connective tissue continuous with the surrounding
tunic.
 Central arteries in the corpora cavernosa branch to
form nutritive arterioles and small coiling helicine
arteries( lead to the cavernous vascular spaces of
erectile tissue.)
 Arteriovenous shunts are present between the central
arteries and the dorsal veins
 Penile erection involves blood filling the cavernous
spaces in the three masses of erectile tissue.
 Triggered by external stimuli to the CNS, erection is
controlled by autonomic nerves in these vascular
walls. Parasympathetic stimulation relaxes the
trabecular smooth muscle and dilates the helicine
arteries (enlarges the corpora cavernosa and causes
them to compress the dorsal veins against the dense
tunica albuginea, which blocks the venous outflow
and produces tumescence and rigidity in the erectile
tissue.)
 Ejaculation: sympathetic stimulation constricts the
helicine arteries and trabecular muscle, decreasing
blood flow into the spaces, lowering the pressure
there, and allowing the veins to
 drain most blood from the erectile tissue.
 At the beginning of an erection acetylcholine from
parasympathetic nerves in the penis causes the
vascular endothelial cells of the helicine arteries and
cavernous tissue to release nitric oxide (NO).
Diffusing into the adjacent smooth muscle cells, NO
activates guanylate cyclase to produce cyclic GMP,
which causes these cells to relax, resulting in
increased blood flow, filling of the cavernous spaces,
and penile erection.
 Erectile dysfunction, or impotence, can result from
diabetes, anxiety, vascular disease, or nerve damage
during prostatectomy.
 The drug sildenafil may alleviate the problem by
inhibiting the phosphodiesterase degrading cyclic
 GMP in the smooth muscle cells of helicine arteries
and erectile tissue.
 The subsequent higher level of cGMP promotes
relaxation of these cells and enhances the neural effect
to produce or maintain an erection.