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Male reproductive function and it’s
regulation
Sharaine Fernando,
Department of Physiology
November 2015
Structure of male reproductive
system
Cross section of the testes
Functions of the male RS
• Gametogenesis (spermatogenesis)
• Deposition of gametes (sperm) in female RS
• Synthesis and regulation of secretion of
hormones
Spermatogenesis
The beginning of a long and a difficult journey........
Spermatogenesis
Wall of Seminiferous tubules
Spermatogonia (44xy)
Primary spermatocytes (44xy)
Secondary spermatocytes (22x / 22y)
Meiosis 1
Meiosis 2
Spermatids
Spermatozoa(Sperm)
Mature in folds of cytoplasm of Sertoli cells
Released to lumen (average 74 days).
FSH, Androgen essential to maintain
spermatogenesis.
512 Spermatids from 1 Spermatogonium.
Spermatids lose excess
cytoplasm and form a tail
Structure of a
sperm
Major regions
1. Head: genetic region;
• Nucleus contains chromosomal
material
• helmet-like acrosome
containing hydrolytic enzymes
that enable the sperm to
penetrate an egg
2. Mid piece: metabolic region;
• mitochondria
3. Tail: locomotor region;
• flagellum
head
Mid piece
tail
Further maturation
• Spermatozoa leaving the testes are not
fully motile
• They continue to mature and acquire
motility during the passage through the
epididymis.
• The ability to move forward (progressive
motility), is acquired in the epididymis.
• involves activation of a unique protein called
CatSper, localized to the principal piece of
the sperm tail
• appears to be a Ca2+
ion channel(alkaline
sensitive) that permits cAMP-generalized
Ca2+
influx
• spermatozoa also express olfactory
receptors, sensitive to odorant-like
molecules produced by ovaries.
• these molecules interact with the sperm
receptors fostering movement of the
spermatozoa toward the ovary (chemotaxis).
The journey continues….
• In the isthmus of the uterine tubes,
capacitation occurs
• This further maturation process involves
two components:
– increasing the motility of the spermatozoa
– facilitating the acrosome reaction
From the isthmus, the capacitated
spermatozoa move to the tubal ampulla,
where fertilization takes place
More about it later!
Blood Testis Barrier
Formed by Tight junction between adjacent Sertoli
cells near basal lamina.
It is not only a structural barrier but a dynamic
functional barrier as well
Functions
1. Prevent entry of large molecules from basal
compartment to the tubular lumen. (steroids,
maturing germ cells)
2. Maintain composition of fluid in seminiferous
tubules. Rich in androgens, oestrogen, K+
,
glutamic & aspartic acids.
3. Protect germ cells from noxious
agents.
4. Prevent entry of developing germ
cells into blood. (Prevent antibody
formation)
5. Establish osmotic gradient. Thus
facilitate movement of fluid in to the
tubular lumen
Synthesis of hormones and their
regulation
• Main hormone- testosterone
• Secreted by Ledig cells into the blood
stream
• High concentration in Sertoli cells
maintained by direct diffusion and by ABP
• Secretion rate is 4 to 9 mg/d (13.9–31.33
mmol/d) in normal adult males.
• 98% of the testosterone in plasma is
bound to protein:
65% bound to a -globulin called gonadal steroid-
binding globulin (GBG) or sex steroid-binding
globulin
33% to albumin
Regulation of secretion of hormones
GnRH
LH, FSH
Sertoli
cells
Ledig
cells
Hypothalamus
Anterior pituitary
testis
Inhibin BTestosterone
T
ABP
1.Follicular stimulating hormone (FSH)
• Trophic to Sertoli cells
• Stimulates secretion of androgen binding
protein (ABP)
• Stimulates secretion of inhibin, MIS
2.Luteininzing hormone
• Trophic to Ledig cells
• Stimulates secretion of testosterone
3.Inhibins
• Inhibit FSH release
Mechanism of action
Testosterone binds to an intracellular receptor
Receptor–steroid complex binds to DNA in the
nucleus, facilitating transcription of genes
In addition, testosterone is converted to
dihydrotestosterone (DHT) by 5α-reductase
in some target cells
• DHT binds to the same intracellular
receptor as testosterone
• DHT also circulates, plasma level about
10% of the testosterone level
• Testosterone–receptor complexes are less
stable than DHT–receptor complexes in
target cells
• DHT formation is a way of amplifying the
action of testosterone in target tissues.
11/24/15 22
Actions of testosterone and dihydrotestosterone
Figure 23.8 Ganong’s 24th
Edition
Summary of effects of testosterone
In fetus - Differentiation of male genital tract.
Differentiation of male external genitalia
(DHT)
Descent of testes.
At puberty- growth & maturation of male RS
Libido
Development of IIry
sexual characteristics
Bone growth
On reproduction - Spermatogenesis
increases libido
Maintain IIry
sexual characters
Regulation of gonadotrophin
secretion(H-P-T axis)
Other effects - Protein anabolic
Erythropoietin secretion
Deposition of sperm in the
female reproductive tract
Erection
• Spinal reflex
• integrating centers in the lumbar segments of
the spinal cord are activated by impulses in
afferents from the genitalia and descending
tracts that mediate erection in response to
erotic stimuli (touch, sight, sound, smell)
• The efferent parasympathetic fibers are in the
pelvic splanchnic nerves (nervi erigentes).
3 cylindrical columns
of erectile tissue
Dorsal: 2 x corpus
cavernosa
Ventral: 1 x corpus
spongiosum
• Efferents release
acetylcholine and
vasodilator vasoactive
intestinal polypeptide
(VIP) as co transmitters
• initiated by dilation of the
arterioles of the penis
• the erectile tissue of the
penis fills with blood, the
veins gets compressed,
blocking outflow
• Nonadrenergic noncholinergic fibers are also present
in the nervi erigentes, containing large amounts of NO
synthase
• NO synthase catalyzes the formation of nitric oxide
• NO activates guanylyl cyclase, resulting in increased
production of cyclic GMP (cGMP)
• cGMP is a potent vasodilator
• NO plays a prominent role in producing an erection
• Erection is terminated by sympathetic vasoconstrictor
impulses to the penile arterioles
Treatment of impotence ?
sildenafil, tadalafil, and
vardenafil inhibit the
breakdown of cGMP by
phosphodiesterases
Ejaculation
Ejaculation is a two-part spinal reflex
emission, due to contraction of muscles in
VasDeferens, prostate and SeminalVesicl,
secretions move to urethra and mix with
sperm to form semen
ejaculation, the propulsion of the semen
out of the urethra at the time of orgasm.
The afferent pathways, mostly fibers from
touch receptors in the glans penis
reach the spinal cord through the internal
pudendal nerves S 2,3,4.
Emission
• sympathetic response
• integrated in the upper lumbar segments
(L1,2) of the spinal cord
• effected by contraction of the smooth
muscle of the vas deferens and seminal
vesicles in response to stimuli in the
hypogastric nerves
• semen is propelled out of the urethra by
contraction of the bulbocavernosus
muscle
• The spinal centers for this part of the reflex
are in the upper sacral and lowest lumbar
segments of the spinal cord
• the motor pathways traverse in the S1to S3
roots in the internal pudendal nerves.
• Climax/orgasm is followed by a period of
muscular relaxation whereby blood flow to
penis is reduced and a latent period (of
minutes to hours) occurs
• During this period the male is unable to
achieve another orgasm.
Seminal fluid
• Volume- more than 2ml
• pH – alkaline
Only a small volume of semen consists of sperm,
but 20-150 million sperm are present with each
ejaculate
• Semen consists of:
• Seminal vesicle secretions: 60%
• Prostate secretions: 30%
• Bulbourethral secretions: 5%
• Epididymal secretions (eg sperm): 5%
What are the factors essential for
spermatogenesis?
• Intact germinal epithelium/supportive cells
• Hormones /Hypothalamo/pituitary/testis
axis
• Optimum temperature
• Nutrients/micro nutrients
• Intact blood testis barrier
Thank you
SGA
• Based on the factors essential for
spermatogenesis, discuss the factors that
affect the fertility of a man?
What factors affect fertility?
• Genetic, infections, trauma
• Disorders of the H/P/T axis, damage to
Leydig cells, androgen receptor defects,
androgen insensitivity
• Tight clothing, posture occupational
exposure to heat, varicocele
• Nutritional deficiencies, transporter defects
• Trauma ,infections
Other factors- multiple mechnisms
• Drugs
• Alcohol/smoking
• Environmental exposure to chemicals.
Irradiation, toxins
• Stress

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Male reproductive system and its regulation

  • 1. Male reproductive function and it’s regulation Sharaine Fernando, Department of Physiology November 2015
  • 2. Structure of male reproductive system
  • 3. Cross section of the testes
  • 4. Functions of the male RS • Gametogenesis (spermatogenesis) • Deposition of gametes (sperm) in female RS • Synthesis and regulation of secretion of hormones
  • 5. Spermatogenesis The beginning of a long and a difficult journey........
  • 6. Spermatogenesis Wall of Seminiferous tubules Spermatogonia (44xy) Primary spermatocytes (44xy) Secondary spermatocytes (22x / 22y) Meiosis 1 Meiosis 2
  • 7. Spermatids Spermatozoa(Sperm) Mature in folds of cytoplasm of Sertoli cells Released to lumen (average 74 days). FSH, Androgen essential to maintain spermatogenesis. 512 Spermatids from 1 Spermatogonium. Spermatids lose excess cytoplasm and form a tail
  • 8. Structure of a sperm Major regions 1. Head: genetic region; • Nucleus contains chromosomal material • helmet-like acrosome containing hydrolytic enzymes that enable the sperm to penetrate an egg 2. Mid piece: metabolic region; • mitochondria 3. Tail: locomotor region; • flagellum head Mid piece tail
  • 9. Further maturation • Spermatozoa leaving the testes are not fully motile • They continue to mature and acquire motility during the passage through the epididymis. • The ability to move forward (progressive motility), is acquired in the epididymis.
  • 10. • involves activation of a unique protein called CatSper, localized to the principal piece of the sperm tail • appears to be a Ca2+ ion channel(alkaline sensitive) that permits cAMP-generalized Ca2+ influx • spermatozoa also express olfactory receptors, sensitive to odorant-like molecules produced by ovaries. • these molecules interact with the sperm receptors fostering movement of the spermatozoa toward the ovary (chemotaxis).
  • 11. The journey continues…. • In the isthmus of the uterine tubes, capacitation occurs • This further maturation process involves two components: – increasing the motility of the spermatozoa – facilitating the acrosome reaction From the isthmus, the capacitated spermatozoa move to the tubal ampulla, where fertilization takes place
  • 12. More about it later!
  • 13. Blood Testis Barrier Formed by Tight junction between adjacent Sertoli cells near basal lamina. It is not only a structural barrier but a dynamic functional barrier as well Functions 1. Prevent entry of large molecules from basal compartment to the tubular lumen. (steroids, maturing germ cells) 2. Maintain composition of fluid in seminiferous tubules. Rich in androgens, oestrogen, K+ , glutamic & aspartic acids.
  • 14. 3. Protect germ cells from noxious agents. 4. Prevent entry of developing germ cells into blood. (Prevent antibody formation) 5. Establish osmotic gradient. Thus facilitate movement of fluid in to the tubular lumen
  • 15.
  • 16. Synthesis of hormones and their regulation
  • 17. • Main hormone- testosterone • Secreted by Ledig cells into the blood stream • High concentration in Sertoli cells maintained by direct diffusion and by ABP • Secretion rate is 4 to 9 mg/d (13.9–31.33 mmol/d) in normal adult males. • 98% of the testosterone in plasma is bound to protein: 65% bound to a -globulin called gonadal steroid- binding globulin (GBG) or sex steroid-binding globulin 33% to albumin
  • 18. Regulation of secretion of hormones GnRH LH, FSH Sertoli cells Ledig cells Hypothalamus Anterior pituitary testis Inhibin BTestosterone T ABP
  • 19. 1.Follicular stimulating hormone (FSH) • Trophic to Sertoli cells • Stimulates secretion of androgen binding protein (ABP) • Stimulates secretion of inhibin, MIS 2.Luteininzing hormone • Trophic to Ledig cells • Stimulates secretion of testosterone 3.Inhibins • Inhibit FSH release
  • 20. Mechanism of action Testosterone binds to an intracellular receptor Receptor–steroid complex binds to DNA in the nucleus, facilitating transcription of genes In addition, testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase in some target cells
  • 21. • DHT binds to the same intracellular receptor as testosterone • DHT also circulates, plasma level about 10% of the testosterone level • Testosterone–receptor complexes are less stable than DHT–receptor complexes in target cells • DHT formation is a way of amplifying the action of testosterone in target tissues.
  • 22. 11/24/15 22 Actions of testosterone and dihydrotestosterone Figure 23.8 Ganong’s 24th Edition
  • 23. Summary of effects of testosterone In fetus - Differentiation of male genital tract. Differentiation of male external genitalia (DHT) Descent of testes. At puberty- growth & maturation of male RS Libido Development of IIry sexual characteristics Bone growth
  • 24. On reproduction - Spermatogenesis increases libido Maintain IIry sexual characters Regulation of gonadotrophin secretion(H-P-T axis) Other effects - Protein anabolic Erythropoietin secretion
  • 25. Deposition of sperm in the female reproductive tract
  • 26. Erection • Spinal reflex • integrating centers in the lumbar segments of the spinal cord are activated by impulses in afferents from the genitalia and descending tracts that mediate erection in response to erotic stimuli (touch, sight, sound, smell) • The efferent parasympathetic fibers are in the pelvic splanchnic nerves (nervi erigentes).
  • 27. 3 cylindrical columns of erectile tissue Dorsal: 2 x corpus cavernosa Ventral: 1 x corpus spongiosum • Efferents release acetylcholine and vasodilator vasoactive intestinal polypeptide (VIP) as co transmitters • initiated by dilation of the arterioles of the penis • the erectile tissue of the penis fills with blood, the veins gets compressed, blocking outflow
  • 28. • Nonadrenergic noncholinergic fibers are also present in the nervi erigentes, containing large amounts of NO synthase • NO synthase catalyzes the formation of nitric oxide • NO activates guanylyl cyclase, resulting in increased production of cyclic GMP (cGMP) • cGMP is a potent vasodilator • NO plays a prominent role in producing an erection • Erection is terminated by sympathetic vasoconstrictor impulses to the penile arterioles
  • 29. Treatment of impotence ? sildenafil, tadalafil, and vardenafil inhibit the breakdown of cGMP by phosphodiesterases
  • 30. Ejaculation Ejaculation is a two-part spinal reflex emission, due to contraction of muscles in VasDeferens, prostate and SeminalVesicl, secretions move to urethra and mix with sperm to form semen ejaculation, the propulsion of the semen out of the urethra at the time of orgasm.
  • 31. The afferent pathways, mostly fibers from touch receptors in the glans penis reach the spinal cord through the internal pudendal nerves S 2,3,4.
  • 32. Emission • sympathetic response • integrated in the upper lumbar segments (L1,2) of the spinal cord • effected by contraction of the smooth muscle of the vas deferens and seminal vesicles in response to stimuli in the hypogastric nerves • semen is propelled out of the urethra by contraction of the bulbocavernosus muscle
  • 33. • The spinal centers for this part of the reflex are in the upper sacral and lowest lumbar segments of the spinal cord • the motor pathways traverse in the S1to S3 roots in the internal pudendal nerves. • Climax/orgasm is followed by a period of muscular relaxation whereby blood flow to penis is reduced and a latent period (of minutes to hours) occurs • During this period the male is unable to achieve another orgasm.
  • 34. Seminal fluid • Volume- more than 2ml • pH – alkaline Only a small volume of semen consists of sperm, but 20-150 million sperm are present with each ejaculate • Semen consists of: • Seminal vesicle secretions: 60% • Prostate secretions: 30% • Bulbourethral secretions: 5% • Epididymal secretions (eg sperm): 5%
  • 35. What are the factors essential for spermatogenesis? • Intact germinal epithelium/supportive cells • Hormones /Hypothalamo/pituitary/testis axis • Optimum temperature • Nutrients/micro nutrients • Intact blood testis barrier
  • 37. SGA • Based on the factors essential for spermatogenesis, discuss the factors that affect the fertility of a man?
  • 38. What factors affect fertility? • Genetic, infections, trauma • Disorders of the H/P/T axis, damage to Leydig cells, androgen receptor defects, androgen insensitivity • Tight clothing, posture occupational exposure to heat, varicocele • Nutritional deficiencies, transporter defects • Trauma ,infections
  • 39. Other factors- multiple mechnisms • Drugs • Alcohol/smoking • Environmental exposure to chemicals. Irradiation, toxins • Stress