MALE REPRODUCTIVE SYSTEM
MALE REPRODUCTIVE SYSTEM
 TO REVIEW THE COMPONENTS OF THE
MALE REPRODUCTIVE SYSTEM
 TO CHARACTERIZE THE GENERAL
ORGANIZATION OF THE TESTIS
 TO UNDERSTAND THE HORMONAL REGULATION
AND PROCESS OF SPERMATOGENESIS
MALE REPRODUCTIVE SYSTEM
 TESTES
 EPIDIDYMIS
 VAS DEFERENS
 SEMINAL VESICLES
 PROSTATE
 BULBOURETHRAL GLANDS
 URETHRA
Male Reproductive System
• Pathway of spermatozoa
– Epididymis
– Ductus deferens (Vas deferens)
– Ejaculatory duct
• Accessory organs
–
–
–
–
–
Seminal vesicles
Prostate gland
Bulbourethral glands
Scrotal sac encloses testes
Penis
The Male Reproductive System in Midsagital View
Figure 28.1
The Male Reproductive System in Anterior View
Figure 28.3
The Structure of the Testes
Figure 28.4
The Epididymus
Figure 28.9
Epididymis and Ductus Deferens
• Epididymis: connection between the testis and
ductus deferens
• Three parts: head (cauda), body, and tail
• Ductus deferens (vas deferens): connects tail
of epididymis to ejaculatory duct
• Ascends within scrotum in the spermatic cord,
into the pelvic region.
The Ductus Deferens and Accessory Glands
Figure 28.10a-e
Seminal Vesicles and Prostate
• Seminal vesicles: enlarged, sac-like
structures which open into ejaculatory
ducts.
• Prostate: lobular structure at base of
bladder.
Male External Genitalia
• Penis: male copulatory organ (also excretion:
elimination of urine)
• Composed of three columns of erectile tissue, each
enclosed by connective tissue
• Scrotum: two separate compartments, each
containing a testis.
• Wall of scrotum: skin, superficial loose connective
tissue, smooth muscle (dartos).
Male Accessory Sex Organs: the Penis
• 3 columns of erectile tissue:
- corpus spongiosum: 1 column, includes
glans penis, and contains the spongy
(penile) urethra
- 2 corpora cavernosa: lateral columns,
forming the dorsum and sides of the penis
The Penis
Figure 28.11
Hormones and Male Reproductive
Function
• FSH (Follicle stimulating hormone)
– Targets sustentacular cells to promote spermatogenesis
• LH (leutinizing hormone)
– Causes secretion of testosterone and other androgens
• GnRH (Gonadotropin releasing hormone)
• Testosterone
– Most important androgen
MALE REPRODUCTIVE SYSTEM
 TESTIS
TUNICA ALBUGINEA
- thick connective tissue capsule
- connective tissue septa divide
testis into 250 lobules
- each lobule contains 1-4
seminiferous tubules and
interstitial connective tissue
(1) SEMINIFEROUS TUBULES
- produce sperm
INTERSTITIAL TISSUE
- contains Leydig cells which
produce testosterone
(2) RECTUS TUBULES
(3) RETE TESTIS
(4) EFFERENT DUCTULES
(5) EPIDIDYMIS
MALE REPRODUCTIVE SYSTEM
 TESTIS
EPIDIDYMIS
LOBULES
TUNICA
ALBUGINEA
TESTIS H&E
SEMINIFEROUS TUBULES
TESTIS H&E
SEMINIFEROUS TUBULES
SEMINIFEROUS TUBULES
INTERSTITIAL
CONN. TISSUE
TESTIS H&E
SEMINIFEROUS TUBULES
SEMINIFEROUS
TUBULES
INTERSTITIAL
CONN. TISSUE
MALE REPRODUCTIVE SYSTEM
 TESTIS
TUNICA VAGINALIS
TUNICA ALBUGINEA
SEMINIFEROUS TUBULES
SEMINIFEROUS EPITHELIUM
- complex stratified epithelium
containing two basic cell populations:
(1) SPERMATOGENIC CELLS
(2) SERTOLI CELLS
MALE REPRODUCTIVE SYSTEM
 TESTIS
SEMINIFEROUS TUBULES
SEMINIFEROUS EPITHELIUM
- complex stratified epithelium
containing two basic cell populations:
(1) SPERMATOGENIC CELLS
stem cells which regularly replicate
and differentiate into mature sperm
as they migrate toward the lumen
(2) SERTOLI CELLS
nonreplicating physical support cells
INTERSTITIAL CONNECTIVE TISSUE
(1) LEYDIG CELLS
produce and release testosterone
MALE REPRODUCTIVE SYSTEM
 SPERMATOGENESIS
SPERMATOGONIA
1º SPERMATOCYTE
2º SPERMATOCYTE
SPERMATIDS
SPERMATIDS
2º SPERMATOCYTE
1º SPERMATOCYTE
SERTOLI CELLS:
- columnar with adjoining lateral processes
- extend from basal lamina to lumen
- Sertoli-Sertoli junctions divide
seminiferous tubules into basal and
adluminal compartments
SERTOLI
CELLS
SPERMATOGONIA
MALE REPRODUCTIVE SYSTEM
 SPERMATOGENESIS
THREE PHASES:
(1) Spermatogonial Phase (Mitosis)
- spermatogonia proliferate by mitotic
divisions to provide stem cells and
cells which will proceed through
spermatogenesis (1º spermatocytes)
(2) Spermatocyte Phase (Meiosis)
- diploid cells (2n) created in spermatogonial
phase give rise to haploid cells (1n)
- Meiosis I (reduction division) and
Meiosis II (equatorial division)
- 1º spermatocytes enter Meiosis I to form
2º spermatocytes which then enter
Meiosis II and result in spermatids
(3) Spermatid Phase (Spermiogenesis)
- spermatid differentiation into spermatazoa
SEMINIFEROUS TUBULES
Basal Lamina
Spermatogonia (stem cells)
2n
2n
2n
mitosis
Daughter cell Type A
spermatogonium
remain at basal lamina
as a precursor cell
Daughter cell Type B Spermatagonium
Moves to adluminal compartment
n
1° spermatocyte
Meiosis I completed
n
n
Meiosis II
2° spermatocyte
n
n
n
n
n
n
n
n
Early spermatids
Late spermatids
MALE REPRODUCTIVE SYSTEM
 SPERMATOGENESIS
THREE PHASES:
(1) Spermatogonial Phase (Mitosis)
(2) Spermatocyte Phase (Meiosis)
(3) Spermatid Phase (Spermiogenesis)
- acrosome formation; golgi granules fuse to
form acrosome that contains hydrolytic
enzymes which will enable the
spermatozoa to move through the
investing layers of the oocyte
- flagellum formation; centrioles and
associate axoneme (arrangement of
microtubules in cilia)
- changes in size and shape of nucleus;
chromatin condenses and shedding of
residual body (cytoplasm)
MALE REPRODUCTIVE SYSTEM
 SPERMIOGENESIS
Mature sperm 60µm long and acquire full motility in epididymis
(1) HEAD
- nucleus and acrosome
(2) NECK
- centriole and connecting piece
(3) TAIL
- middle piece
(axoneme, outer dense fibers, mitochondial sheath)
- principal piece
(axoneme, outer dense fibers, fibrous sheath)
- end piece
(axoneme)
MALE REPRODUCTIVE SYSTEM
 SPERMIOGENESIS
Maturation of Sperm
• Sperm leaving the testis and entering the
epididymis are nonmotile and not capable
of fertilization.
• Sperm acquire motility and final
maturation as they travel through the
epididymis.
Time Span of Sperm Development
• It takes about 70 days to develop from
spermatogonia to spermatozoa.
• It takes another 14 days to travel through
epididymis to the ejaculatory duct.
• Illness and exposure to toxic agents can have a
delayed effect on quality of sperm produced.
Production of Semen
• Semen is composed of spermatozoa and the
secretory products of the seminal vesicle (60%)
and prostate (30%).
• Products of the seminal vesicle and prostate
include
- fructose (metabolized for energy by sperm)
- prostaglandins (uterine contractions)
- coagulating and decoagulating factors
- antibacterial agents
- pH adjusters (acids and bases)
• The bulbourethral gland secretes an alkaline
mucus, neutralizes acidity in the urethra and
provides lubrication
Capacitation of Sperm
• To fertilize an egg, the spermatozoa must undergo
capacitation in the female reproductive tract
following ejaculation.
• Capacitation results in:
- increased velocity of sperm movement
- release of enzymes which allow sperm to reach
the oocyte and penetrate it (acrosome reaction)
- requires 2 to 6 hours
(sperm may remain alive in the reproductive tract for
days)
Male Sexual Response
• Three distinct phases have been identified;
arousal, emission, and ejaculation.
• Arousal: erotic thoughts or physical stimulation
result in activation of the parasympathetic system
(via pelvic splanchnic nerves).
- increased production of nitric oxide
- nitric oxide activates soluble guanylate cyclase,
resulting in increased production of cGMP
- cGMP causes vasodilatation of blood vessels in
the penis, resulting in increased blood flow and
erection
Male Sexual Response
• Emission: Sympathetic stimulation causes
peristaltic contractions of the ampulla of the
ductus deferens, the seminal vesicles, and the
prostate. Thus, spermatozoa and seminal fluids
enter the prostatic urethra.
• At the same time, the internal urethral sphincter
closes off the bladder to prevent retrograde
ejaculation
Male Sexual Response
• Ejaculation: Contractions of two skeletal muscles:
- ischiocavernosus: contractions against the
erectile tissue of the penis
- bulbocavernosus: contractions push semen from
base of penis to urethral opening
(note that these are skeletal muscles under
sympathetic control)
Role of Testosterone in Male Sexual
Response
• Testosterone increases libido (sexual thoughts and
desires).
• However, testosterone plays little role in capacity
of men to have sexual intercourse.
• Impotence (inability to achieve or maintain
erection) can be due to physical causes
(circulatory problems, drugs, alcohol, trauma,
illness) or psychological state (depression,
anxiety, stress).
• Viagra: inhibitor of cGMP-specific
phosphodiesterase (increases cGMP levels).
Mechanism of Action of Viagra
arousal
parasympathetic stimulation
Viagra
nitric oxide
cyclic GMP
PDE5
5’ GMP
Hormonal Regulation
of the Male Reproductive
System
MALE REPRODUCTIVE SYSTEM
 HORMONAL REGULATION OF
MALE REPRODUCTIVE FUNCTION
HYPOTHALAMUS REGULATES ACTIVITY OF
ANTERIOR PITUITARY (ADENOHYPOPHYSIS)
ADENOHYPOPHYSIS SYNTHESIZES HORMONES
(LH and FSH) THAT MODULATE ACTIVITY OF
SERTOLI AND LEYDIG CELLS
Luteinizing Hormone (LH): stimulates testosterone
production by Leydig cells
Follicle Stimulating Hormone (FSH): stimulates production of sperm
in conjunction with testosterone by regulating activity of Sertoli cells
SERTOLI CELLS STIMULATED BY FSH AND TESTOSTERONE RELEASE
ANDROGEN BINDING PROTEIN WHICH BINDS TESTOSTERONE;
THEREBY INCREASING TESTOSTERONE CONCENTRATION WITHIN THE
SEMINIFEROUS TUBULES AND STIMULATING SPERMATOGENESIS
Regulation of LH and FSH Synthesis
and Release by GnRH
• GnRH stimulates both the synthesis and release of
gonadotropins.
• GnRH is released from the hypothalamus in a
pulsatile manner (once ever 30-45 minutes in adult
men).
• Constant, high levels of GnRH will DECREASE
gonadotropin release, by down-regulation of GnRH
receptors.
LH
GnRH
LH
Mechanism of GnRH Action on Pituitary
Gonadotroph Cells
• GnRH binds to a G protein-coupled receptor.
• Binding of GnRH to receptor results in activation
of phospholipase C.
• Get increased production of IP3 and DAG.
• Increased IP3 leads to release of LH, FSH.
• DAG activates PKC, which increases synthesis of
LH and FSH.
Mechanism of GnRH Action on Pituitary
Gonadotroph Cells
Calcium
GnRH
R
release
synthesis
Protein Kinase
C
LHb mRNA
Feedback Regulation of LH and FSH by
Gonadal Steroids
• Testosterone (and estradiol, from peripheral
conversion) exerts negative feedback effects on
LH and FSH synthesis and release in the male.
- decreased pulsatile release of GnRH
- decreased pituitary response to GnRH
stimulation
• Males do NOT show positive feedback responses
of LH to high levels of estradiol.
Regulation of LH and FSH by GnRH
Alone?
• To date, only one hypothalamic releasing factor
controlling release of LH and FSH has been found
(GnRH).
• There are cases when LH release is different from
FSH release. How can this happen?
• Two possibilities:
- influence of GnRH pulse frequency on LH
versus FSH levels
- other factors which control FSH levels exist
Influence of GnRH Pulse Frequency on
LH versus FSH Release
• GnRH is released from the hypothalamus as discrete
pulses.
• High frequency pulses (once every 30 minutes) result
in stimulation of LH release, with less release of FSH.
• Low frequency pulses (once every 60 minutes) result
in stimulation of FSH release, with less release of LH.
• Thus, regulating the pulse frequency of GnRH release
can give preferential release of LH or FSH.
LH FSH
GnRH
LH FSH
Influence of Gonadal Peptides on
Synthesis and Release of FSH
• The testis and ovary produce two hormones which
influence FSH, but not LH release.
• Inhibin: preferentially inhibits the synthesis and
release of FSH from the anterior pituitary (no
effect on LH).
• Activin: preferentially stimulates the synthesis and
release of FSH from the pituitary (no effect on
LH).
• Both act at the level of the pituitary (do not
influence GnRH release).
Regulation of Inhibin Production
• Inhibin production from Sertoli cells is stimulated
by FSH.
• However, a real role of inhibin and activin from
the testis on FSH release is not clear in adult males
(blocking inhibin action doesn’t increase FSH).
• There is evidence that inhibin and activin are also
produced locally from the pituitary (and possibly
hypothalamus), providing local control of FSH
release.
Mechanism of Action of LH and FSH on
Testicular Cells
• Leydig cells have receptors for LH, but not for
FSH.
• Sertoli cells have receptors for FSH, but not for
LH.
• Both the LH and FSH receptor are G proteincoupled receptors, with a fairly high degree of
homology.
• Specificity of hormone binding is determined by
the amino terminus extracellular domains.
The Structure of LH and FSH
• LH and FSH are composed of two subunits.
• The  subunit is shared by FSH, LH, TSH, and
hCG
• Distinct ß subunits confer specific receptor
binding and biological activity of these
glycoproteins
• Each subunit is glycosylated, folded, and joined
to its corresponding subunit
Binding Specificity Due To Extracellular
Domains of the LH and FSH Receptors
LH
cyclic AMP
FSH
cyclic AMP
Mutant LH/FSH Receptor
+
LHR Extracellular
FSHR Transmembrane and
Domain
Intracellular Domains
LH
cyclic AMP
Mechanism of Action of Gonadotropins
• Gonadotropin receptors are coupled to Gs
- increased cAMP
- leads to activation of protein kinase A
- phosphorylation of cAMP response element
binding protein (CREB), a transcription factor
Actions of FSH on the Testis
• FSH acts on Sertoli cells
- stimulate spermatogenesis
- increase production of inhibin
- increase production of androgen-binding protein,
which binds to testosterone to increase local levels
in the testis and epididymis
• FSH also augments effects of LH on testosterone
production (possibly through peritubular cells?)
Actions of LH on the Testis
• Primary action: stimulate testosterone production
- binds to LH receptors on Leydig cells
- increases conversion of cholesterol esters to free
cholesterol
- increases expression of steroidogenic acute
regulatory protein (cholesterol transfer)
- increases expression of P450 side chain cleavage
to stimulate steroidogenesis
- increases expression of 17-hydroxylase
Transport and Metabolism of
Testosterone
• Testosterone is bound to binding proteins in the
plasma
- 45% bound to TeBG (not biologically available)
- 35% bound to albumin, 16% to other proteins
- only 4% free in blood
• T can be metabolized to other hormones, or
conjugates
- peripheral conversion to E2 or DHT
- conjugation in liver, excretion via kidney
Actions of Testosterone
• Testosterone acts on a wide variety of tissues
during sexual differentiation and puberty, and in
the adult (see previous lecture).
• In the testis, a major action of testosterone is the
maintenance of spermatogenesis, via stimulation
of Sertoli cells.
• The actions of T are mediated through an
intracellular androgen receptor, which acts as a
transcription factor.
MALE REPRODUCTIVE SYSTEM
 TESTIS
TUNICA ALBUGINEA
- thick connective tissue capsule
- connective tissue septa divide
testis into 250 lobules
- each lobule contains 1-4
seminiferous tubules and
interstitial connective tissue
(1) SEMINIFEROUS TUBULES
- produce sperm
INTERSTITIAL TISSUE
- contains Leydig cells which
produce testosterone
(2) RECTUS TUBULES
(3) RETE TESTIS
(4) EFFERENT DUCTULES
(5) EPIDIDYMIS
EPIDIDYMIS
EFFERENT DUCTULES
MALE REPRODUCTIVE SYSTEM
 EFFERENT DUCTULES
CONNECT RETE TESTIS WITH EPIDIDYMIS
IRREGULAR LUMINAL APPEARANCE DUE
TO TALL CILIATED CELLS AND SHORT
NON-CILIATED CELLS
CILIATED CELLS BEAT TOWARD EPIDIDYMIS;
THIN LAYER OF SMOOTH MUSCLE ALSO AIDS
MOVEMENT INTO EPIDIDYMIS
MALE REPRODUCTIVE SYSTEM
 EPIDIDYMIS
RECEIVES EFFERENT DUCTULES
DIVIDED INTO HEAD, BODY, AND TAIL
PSEUDOSTRATIFIED EPITHELIUM CONSISTING
OF PRINCIPAL AND BASAL CELLS
SMOOTH MUSCLE IN HEAD AND TAIL
CONTRACT SPONTANEOUSLY; SMOOTH
MUSCLE IN TAIL REQUIRES SYMPATHETIC
INNERVATION FOR CONTRACTION
EPIDIDYMIS
STEREOCILIA
MATURE SPERM
EFFERENT DUCTULES
EPIDIDYMIS
EFFERENT
DUCTULES
EPIDIDYMIS
EPIDIDYMIS
MALE REPRODUCTIVE SYSTEM
 VAS DEFERENS
CONNECTS EPIDIDYMIS WITH
SEMINAL VESICLES
PSEUDOSTRATIFIED COLUMNAR EPITHELIUM
SMOOTH MUSCLE ARRANGED IN 3 LAYERS
SMOOTH MUSCLE CONTRACTION VIA
SYMPATHETIC STIMULATION DURING
EJACULATION
MALE REPRODUCTIVE SYSTEM
 VAS DEFERENS
VAS DEFERENS H&E
MALE REPRODUCTIVE SYSTEM
 SEMINAL VESICLES
MUCOSA HIGHLY FOLDED
EPITHELIUM PSEUDOSTRATIFIED
SECRETIONS ARE HIGH IN
FRUCTOSE AND BASIC
REGULAR SMOOTH MUSCLE
CONTRACTS DURING EJACULATION
MALE REPRODUCTIVE SYSTEM
 SEMINAL VESICLES
EPITHELIUM PSEUDOSTRATIFIED
MALE REPRODUCTIVE SYSTEM
 PROSTATE
SIMPLE OR PSEUDOSTRATIFIED
COLUMNAR EPITHELIUM
30-50 TUBULOALVEOLAR GLANDS
WHICH EMPTY INTO URETHRA
PROSTATIC SECRETIONS RICH IN
CITRIC ACID, ACID PHOSPHATASE,
AND PROTEOLYTIC ENZYMES
MALE REPRODUCTIVE SYSTEM
 PROSTATE
SIMPLE OR PSEUDOSTRATIFIED
COLUMNAR EPITHELIUM
MALE REPRODUCTIVE SYSTEM
 PROSTATE
PROSTATIC CONCRETIONS
- precipitation of secretory product
MALE REPRODUCTIVE SYSTEM
 URETHRA
PROSTATIC, MEMBRANOUS, SPONGY (PENILE)
PENIS
CC
CC
URETHRA
CS
PENIS
ERECTILE
BODIES