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Male reproductive system

❑ STRUCTURE
• Loops of convoluted tubules (seminiferous tubules (ST))
• Both end to head of epididymis
• Spermatogenesis occur at the wall of ST
• Interstitial cells of Leydig: secretes testosterone.
• Sertoli cells secretes ABP (FSH-dependent), inhibin, MIS and estrogen
• Counter current system of testosterone and heat exchange exist between the
spermatic arteries and veins.
Gametogenesis
❑Blood/testes barrier (see next slide)
▪ Tight junction between adjacent Sertoli ❑COMPOSITION OF THE luminal
cells near the basal lamina.
fluid
▪ Prevent movement of large molecules
from interstitial tissues and basal • High androgens
compartment to the adluminal or
luminal part of the tubule. • High Inositol
▪ Steroids penetrates with ease • High potassium
▪ Proteins also passes form the Sertoli cells • High estrogens
to the Leydig cells in a paracrine fashion.
▪ Prevent crossing of blood-borne noxious • Glutamic and aspartic acid
substance to the testes
• Little protein and glucose
▪ Prevent movement of germ cells anti-
genic products.
▪ Create osmotic gradient for the
formation of luminal fluid
Spermatogenesis
SPERM

❑Sperm: Motile cell, rich in DNA


Puberty
• Head: mostly chromosome material
• Acrosome: covering the head as a cap
• Rich in lysosome-like substances
74 days • Help in sperm penetration of the ovum
during fertilization
512 spermatids • Mid piece: proximal part of the tail
wrapped with a sheath of mitochondria.
• Tail: Help in the propulsion of the sperm
in the female reproductive system.
Spermiogenesis
• Final stage of spermatogenesis, where spermatids develop into mature
spermatozoa
• Occur in the deep fold of the cytoplasm of Sertoli cells
• FSH act on Sertoli cells to facilitate last stage of maturation of spermatids
• Sperm is concentrated in the rete testes of the epididymis, and fluid is
reabsorbed.
• Sperm required 18 to 24 hours to acquire motility in the epididymis
• The sperm expresses estrogen receptors and luminal fluid contains a high
estrogen level
• The principal piece matures in the epididymis and acquires the ability to move
forward through the activation of a unique protein “CatSper” (see figure next
slide)
• The head also expresses olfactory receptors
• The process from spermatogonia to spermatids is androgen-independent
• The process from spermatids to spermatozoa (Spermiogenesis) is androgen
dependent.
• Each testes forms ~60 million sperms everyday
• Sperms are stored for up to 1 month
• Sperms becomes motile after ejaculation
• Final maturation occurs in the oviduct.
• They undergo capacitation:
• Increase in motility
• Preparation of acrosome reaction
• Capacitated sperm moves rapidly to ampullas,
• where fertilization occurs
Effect of temperature in spermatogenesis

• Testicular temperature is kept at 32° for optimal spermatogenesis due to


• Circulating air around the scrotum
• Heat exchange in a counter-current fashion between spermatic arteries and
veins
• Sperm count is higher during cold weather
• Sperm lives for 24 to 48 hours at body temperature
• At lower temperature can be stored for several weeks
• At be stored for years below -100°C
SEMEN Composition of Semen
• Fluid ejaculated at the time of orgasm
in males.
• Content:
• Secretions from seminal vesicles,
prostate, Cowper’s gland, and urethral
glands
• Vol: 2.5 to 3 mL
• Normal sperm: 100 million per 1 mL
• 50% sterile men: 20-40 million per 1 mL
• 100% sterile: less than 20 million per 1
mL
• Abnormal sperm causes infertility
• Sperm moves at a speed of 3 mm/min
in the female genital tract to reach the
oviduct
Male sex hormones
❑Testosterone
• Testosterone is a C19 steroid with OH group in position 17.
• Synthesized from cholesterol and androstenedione (adrenal cortex)
in Leydig cells (next slide)
• Leydig cells contain 17a-hydroxylase.
• Secretion of testosterone is under the control of LH acting on LH-
serpentine receptors in Leydig cells
• Daily secretion is 4-9 mg in normal adults males
• Also secreted in females from their ovaries and adrenal gland
Synthesis of testosterone
Transport and metabolism
❑ Transport
• 65% bound to gonadal steroid binding globulin (GBG)
• 33% bound to plasma albumin
• 2% free
❑ Plasma level
• 300-1000 ng/dL in adult men, declines with age
• 30-70 ng/dL in adult women
❑ Excretion
• Converted to 17-ketosteroid in the liver (androsterone and
etiocholanolone)
• Excreted in urine
Actions

• Inhibit the secretions of pituitary Lh


• Develop and maintain male secondary sexual characteristic (see next
slide)
• Increase protein synthesis promoting growth
• Causes Na+, K+, H2O, Ca2+, SO4-, PO2- retention
• Increases size of kidneys
• Increase libido
• Maintain spermatogenesis together with FSH
Male secondary sexual characteristics (Effects of androgens)
Mechanism of actions • Binds to intracellular receptor
• The receptor-steroid complex bind to
DNA
• Facilitating the transcription of genes
• Testosterone is converted to
dihydrotestosterone (DHT) by 5a-
reductase in some targets cells.
• Dht: amplifies the action of
testosterone
• Human have 2 5-a reductase
• Type 1 5a-reductase: present
throughout skin and the dominant
enzyme in scalp.
• Type 2 5a-reductase: present in
genital skins, the prostate, and other
genital tissues
• Testosterone-receptor complex causes the maturation of wolffian duct
(male internal genitalia), muscle mass, development of male sex drive
• DHT-receptor complex causes formation of male external genitalia ( in-
utero)
• DHA-receptor complex causes enlargement of the prostate, and penis,
facial hair, acne, temporal recession of the hair (at puberty)
• Type 2 5a-reductase inhibitor (finasteride) can be used to treat benign
prostatic hyperplasia
Temporal recession
Control of testicular functions
• FSH and testosterone maintain gametogenic functions
of the testes
• FSH act on Sertoli cells to cause secretion of ABP and
inhibins
• Inhibin inhibit the secretion of FSH
• LH is tropic to Leydig cells and stimulate the
production of testosterone
• Testosterone inhibits the production of LH
• Hypothalamic lesions causes atrophy of the testes
• Castration raises the plasma level of gonadotropins
• Testosterone administration cause decreased sperm
count.
Inhibins and activins
❑inhibins ❑Activins
• Produce by Sertoli cells in males, granulosa • Stimulates the production of FSH
cells in females • bAbB, bAbA, and bBbB
• Two subtypes: inhibin A (abA) • Involved in development of WBC in bone
marrow
and inhibin B (abB) • Development of mesoderm in-utero
• Inhibin B is the most active form • Inactivated by binding to plasma a2-
• Inhibin as future male contraceptives macroglobulin
• Inactivated in tissue by binding to follistatins
• Inactivated by binding to plasma
a2-macroglobulin
MALE SEXUAL ACT
❑Erection
• Initiated by dilation of arterioles of the penis, which compresses the vein
and blocks the outflow of blood, adding to the turgor of the organ
• Integrating centre in the lumbar segment of SC
• Afferents: sensory impulse from genitalia and erogenic psychologic stimuli from the
descending tract
• Efferent: Pelvic splanchnic nerve (nervi erigentes)-parasympathetic (Ach and VIP)
• Non-cholinergic/non-adrenergic nerves secretes NO, contain NO synthase
• NO activate guanylyl cyclase (GC)
• GC produces cGMP
• cGMP cause vasodilatation (see next slide)
• cGMP is broken down by phosphodiesterase (PDE5) causing collapse of the penis
• Erection is terminated by the sympathetic vasoconstrictor impulses to the
arterioles of the penis
Erection

Ejaculation
ERECTILE TISSUE OF THE PENIS
• cGMP relaxes the arterioles and
the trabecular meshwork of
smooth muscles in the erectile
tissue (corpora cavernosa and
corpus spongiosum)
• The erectile tissue consists of large
cavernous sinusoids becomes
dilated when arterial blood flow
rapidly into them under pressure
• The erectile body are surrounded
by strong fibrous coats
❑Ejaculation: Sperm moves from the head of the epididymis to the
tail of vas deferens to the body of the urethra (prostate urethra) and
out of the body.
❖Two-part spinal reflex
➢ EMISSION: movement of the semen into the urethra.
• Sympathetic reflex (hypogastric nerve)
• Integrated upper lumber segment of the spinal cord
• Effected by contraction of the smooth muscle of vasa differentia and seminal vesicles
➢ EJACULATION PROPER: propulsion of the semen out of the urethra at the time of orgasm.
• Due to impulses from touch receptors in the glans penis that reach the spinal cord
through the internal pudendal nerve.
• Spinal reflex center (upper sacral and lower lumbar)
• Propelled out of the urethra by contraction of the bulbocavernosus muscle via motor
pathways (1-3rd sacral segment of the spinal cord) and the internal pudendal nerve.
• Carbon monoxide may be involved in ejaculation
• The nerves express heme oxygenase-2 (HO2)
❑ PSA
• Prostate specific antigen
• A 30-kDA serine protease
• Hydrolyzes the sperm motility inhibitor (Semenogelin)
• Elevated plasma PSA occurs in prostate cancer and benign prostatic hyperplasia
❑Resolution
• Disappearance of male sexual excitement and cessation of erection
• Occur 1 to 2 minutes after male orgasm
Abnormalities of testicular functions
❑Cryptorchidism
• Undescended testis
• Testes develop in abdominal cavity, migrate to the scrotum through
inguinal region
• 10% in new born males
• Descent spontaneously
• 2% at age 1 yr.
• 0.3% at puberty
• Treated with gonadotropins
• Can lead to testicular tumour if left undescended
• Can lead to sterility due to damage to spermatogenic epithelium
❑Male hypogonadism In children
In adults ❖Eunuchoidism
❖Hypergonadotrophic hypogonadism • Leydig cells deficiency
• Testicular diseases/castration • Characteristically tall at age 20
• Narrow shoulders and small muscles
• Gonadotrophins levels are elevated (female configuration)
• Secondary sex characteristics regress • Small genitalia
slowly • Voice high pitched
• Voice remains deep (larynx remains • Axillary hair
enlarge)
• Pubic hair ( female escutcheon)
• Loss of libido
❖Hypogonadotrophic hypogonadism
• Ability to copulate persist for some (Kallmann’s syndrome)
time • Disease of the pituitary or
• Hot flushes hypothalamus
• Irritable, passive and depressed • Gonadotropins level are depressed
❑Congenital 5a-reductase deficiency
• mutation in Type 2 5a-reductase
• Common in the Dominican republic, Papua New Guinea, Turkey,
Egypt
• Male pseudohermaphroditism
• Male internal genitalia including testes
• Female external genitalia (raise as females)
• LH surge at puberty causes increase testosterone release causes
male body contour and libido
• Less facial and body hair.
• Clitoris enlarge (“Penis at 12 syndrome” or “Guevedoces”)

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