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Male reproduction

Dicky Moch. Rizal


Department of Physiology, Fac. Of
Medicine, GMU
dickymd@yahoo.com
Male Reproductive Anatomy and
Physiology
200+ genes
50 million base pairs
50% determined
The Y chromosome contains a gene
called SRY (for sex-determining region of
Y).

female
12 weeks
14 weeks
Fetal external genitals: male

15 weeks 16 weeks
Between the 28th and 35th week of pregnancy,
the gubernaculum elongates through a
passageway at the base of the abdominal cavity
(inguinal canal), over the pelvic bone and into
the scrotum.
The gubernaculum becomes shorter and thicker
and acts as a guide, keeping the inguinal
passage open as the testis descends. Once the
testis is in position in the scrotum, the
gubernaculum withers away.
Testicular Compartmentalization
Spermatogenesis: Sperm
Production in the Testis
Spermatozoa Structure and
Functions in Review
Palermo et al., 1997
Sertoli Cell Function
The role of epydidymis :
Store
maturation
Absorption

Under Androgen influenced


Semen Analysis:
World Health Organization
Guidelines
Parameters Normal range
Volume 1.5 - 5 mL
Sperm conc. >20 million/mL
Sperm motility >50%
Sperm morphology >30% normal forms
Leukocyte density <1 million/mL

Need at least 2 S/As (parameters are highly


variable)
Semen Analysis:
World Health Organization
Guidelines
Parameters Normal range Volume 1.5 -
5 mL
Sperm conc. >20 million/mL
Sperm motility >50%
Sperm morphology >30% normal forms
Leukocyte density <1 million/mL

Need at least 2 S/As (parameters are highly


variable)
Semen Analysis:
World Health Organization
Guidelines
Parameters Normal range Volume 1.5 -
5 mL
Sperm conc. >20 million/mL
Sperm motility >50%
Sperm morphology >30% normal forms
Leukocyte density <1 million/mL

Need at least 2 S/As (parameters are highly


variable)
Semen Analysis:
World Health Organization
Guidelines
Parameters Normal range Volume 1.5 -
5 mL
Sperm conc. >20 million/mL
Sperm motility >50%
Sperm morphology >30% normal forms
Leukocyte density <1 million/mL

Need at least 2 S/As (parameters are highly


variable)
The role of male accesory gland
Prostate
Seminal vesicle
Cowpery
Regulation of Spermatogenesis
Testicular Cell Interactions
Hypothalamic-Pituitary regulation of
Testicular Function
Synthesis of Androgens

Cholesterol serves as the substrate for P5


biosynthesis in the Leydig cells.

Conversion of P5 to 17-hydroxylated steroids


provides the steroidogenic predominant
pathway in testicular tissue.

The 17-hydroxysteroids are converted by


side chain cleavage to 17 ketosteroids and
these in turn are converted to testosterone.
Testosterone is the principal steroid
produced by Leydig cells.

Androstenedione and
dehyrdorepiandrosterone are also
produced but the physiological
potencies are very low.
Synthesis of Androgens

Although some androgens are 17-


ketosteroids not all 17-ketosteroids are
androgens and not all androgens are 17-
ketosteroids.
In some tissues, testosterone is converted to
either dihydrotestosterone (DHT) or E 2 which
are the biologically active steroids in these
tissues.
Male Sex Steroid Synthesis
Major Testicular Steroids
Almost 100% of the testosterone in the
blood is bound to protein; ~ 40% bound
to SBG about 40% bound to albumin
and 17% to other proteins.
Roles of Androgens

Testicular androgens play a role in


differentiation and development of
male urogential system, accessory
sex organs and external genitalia.
Many tissues respond directly to
testosterone, but this must be
converted to either DHT or E2 to
mediate its actions.
After the initial actions of T in early
fetal development, the gonads
remain quiescent until puberty, when
gonadotropins increase for
spermatogenesis and 2o sex
characteristics.
Spermatogenesis

FSH and testosterone are required for


the intitiation of spermatogenesis.
Administration of FSH to immature or
mature hypox rats increases the size of
testes but does not accelerate the
appearance of mature sperm or
increase secretory activity of Leydig
cells. For this testosterone is needed.
Spermatogenesis can be maintained in
hypox rats if T is administered but its
intitiation at puberty requires FSH.
Resumption of spermaotgenesis after
hypox also rquires FSH.
Spermatogenesis
In immature animals, FSH increases the
number of Sertoli cells.
FSH is required for the normal
reinitiation of sperm production during
the breeding season in monkeys.
FSH binding with Sertoli cell membrane
receptors results in cAMP production
and synthesis of an androgen binding
protein (ABP).
Spermatogenesis

ABP is then secreted into the lumen of


the S.T.

In response to LH, the Leydig cells


make T which gets into the circulation
and is taken up by the Sertoli cell. T is
able to get across the blood-testis
barrier which first appears at puberty.
T is then bound to ABP to sequester T
close to the spermaotocytes whose
maturation is androgen dependent.
Within the lumen, ABP function to
transport T to the epididymis.
Nervous System
Testicular androgens exert a tonic inhibitory
feedback on AP secretion.
Nuclear androgen-binding sites are present in
the brain of vertebrates, and they represent a
loci of androgen activation of sexually related
behavior.
Implantation of androgens in specific areas of
the brain induce copulatory behavior in fowl.
T can alter preoptic neuron responses to
electrical stimulation of the olfactory bulb and
to natural sexual odors.
2 Sex Characteristics
o

Puberty is the last phase of sexual


maturation, a process where an individual
acquires reproductive competency.
Dimorphic 2o sex characteristics include
changes in the integument: skin color,
hair color, distribution, coarseness,
development of horns, antlers, claws.
Androgens affect courtship behaviors
such as aggression and vocalization.
Sex Organs
Accessory sex glands are dependent on
testosterone to enable them to contribute
secretory products to seminal plasma.
Androgens increase the content of ER
within cells of the prostate, seminal
vesicles, and bulbourethral glands.
Effects of T on the prostate gland is
augmented by Prl, which is without effect
in the castrated animal.
Penis and scrotum enlarge in response
to T or DHT.
Skin
Sebaceous gland activity is stimulated
by androgens most likely derived from
testosterone.
Coarseness of hair and pattern of hair
growth is increased by androgens.
Androgens stimulate hair growth in the
axilla, pubic area and chin.
Androgens may cause baldness in
individuals with a genetic predisposition.
Skin
It has been shown that there is greater
conversion of DHEA into androstenedione, T,
and DHT in human sebaceous glands and
greater activity of 3 -HSD activity in
sebaceous glands of a bald scalp than in
hairy scalp.
Greater 3 -HSD activity and increased
androgen binding capacity may provide a
biochemical explanation for androgenic
alopecia.
Anabolic Actions
Major extragenital site of androgen
action is skeletal muscle.
Skeletal muscle cannot convert T to
DHT so it is likely that T has a direct
anabolic effect on muscle.
Myotropic actions of androgens result
from their ability to increase retention
of dietary N2 through protein synthesis.
Anabolic Steroids
Anabolic actions of androgens may
occur due to competition for cytosolic
glucocorticoid receptors (which work
to enhance protein catabolism).
Androgens are able to exert trophic
effects on skeletal & cardiac muscle in
subjects with low circulating levels of
testosterone.
Most animal studies indicate that
anabolic steroids are ineffective in this
situation.
Continuous high doses of anabolic
steroids produce a large number of
side effects.
Aging

There is an age associated decrease in


serum T levels in healthy men. T is
needed to maintain libido, 2o sex
characteristics and aggressive behavior.

Young men with abnormally low T,


hypogonadism, suffer losss of bone,
muscle, enrgy and libido. T therapy can
reverse these symptoms.
Testosterone from birth..
Testosterone level
DHEA and testosterone level
LH and FSH until 35 yo
Muscle mass is increased in elderly
men taking T but it might also
enhance the growth of the prostate,
thicken the blood due to increases in
RBC, increase water retention,
hepatotoxicity and development of
polycythemia or gynecomastia
A BRIEF ANATOMY & PHYSIOLOGY

Male Sex Organ Anatomy


Mechanism of Erection
Stimulus Erektogenik Stimulus erektolitik

Imajinasi
penciuman Cerebral cortex
Imajinasi,
Penglihatan Cemas,
pendengaran
Perabaan PVN Ketakutan,
Depresi

pelepasan neurotransmiter
Nitric oxide, dopamine,
Serotonine,oxytocine Spinal cord

Neural erectile signalling


Penile erection
A BRIEF ANATOMY & PHYSIOLOGY

Male Sexual Stimuli Process


1. Erectogenic 2. Neural
stimulus initiation
Hypothalamus
Psychogenic sympathetic erection center
4. Smooth (Th11/12-L2/3)
muscle
relaxation Bulb of corpus spongiosum
Bulb of corpus
Reflexogenic
parasympathetic
erection center
(S2-S4)

3. Cellular
activation
Penis
Fisiologi Ereksi
1. Fase O : fase flaccid
2. Fase 1 : fase pengisian
3. Fase 2 : fase tumensensi
4. Fase 3 : fase ereksi penuh
5. Fase 4 : fase ereksi rigid
6. Fase 5 : fase detumesen awal
7. Fase 6 : fase detumesen lambat
8. Fase 7 : fase detumesen cepat

Flaccid Erect
The role of PDE 5 inhibitor
in Penile Smooth Muscle Contractility

Adapted from Lue NEJM , 2000, 32(24):1802-


1813
Erectile and neural aspects
20 30 40 50 60
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