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DEVELOPMENT OF THE MALE
REPRODUCTIVE SYSTEM
Dr. Sahar Hafeez – MD
drsaharhafeez@yahoo.com
2016
LEARNING OBJECTIVES
The students should be able to;
• Briefly describe the process of the arrival of Primordial germ cells with in the genital ridges
• Discuss the formation of the ‘primitive sex cords’
• Discuss the significance and role of SRY gene in the development of gonads
• Enumerate the genital duct systems existing in the ‘indifferent gonad stage’.
• Discuss in detail, the differentiation of Testes and the male duct system.
• Briefly discuss the most common congenital malformations of the male reproductive tract
• Briefly discuss the differentiation & malformations of external genitalia in males.
INTERMEDIATE MESODERM
1. Paraxial mesoderm
2. Splanchnopleuric mesoderm
4. Somatopleuric mesoderm
5. Intermediate mesoderm
3. Gut Endoderm
6. Notocord
7. Extra embryonic cavity
8. Dorsal Aortae
9. Neural tube
The Main source of origin is ;
• The kidneys, ureters and Reproductive system
develop from Intermediate mesoderm.
• Urinary bladder and urethra develop from
gut endoderm (the urogenital sinus)
The beginning
• In the 3rd wk of IUL,
primordial germ cells (PGC)
appear along with the
endodermal cells in the wall of
yolk sac close to the dorsal
mesentery of hind gut.
• They arrive near the genital
ridges at the beginning of the
5th week and invade the ridges
in the 6th week of
development.
Migration of PGC from yolk sac to the gonadal ridges takes place
b/w the 4 – 6 wks of IUL
Anatomic relationship between the genital and urinary systems
1. Coelomic epithelium
2. Intermediate mesoderm (in proliferation)
3. Gonadal cord
4. Primordial germ cells (PGC)
5. Mesenchyme
6. Allantois
7. Vitelline duct
8. Intestine
9. Dorsal mesentery
10. Genital ridge
11. Nephrogenic cord
12. Mesonephric duct (Wolff)
13. Mesonephric tubule
14. Aorta
• Although, the sex of the embryo
both chromosomally & genetically is
established at the very first day of
conception (at the time of fertilization), the
developing gonads stay in an
indifferent state till the 7th wk of
IUL
• Shortly before the arrival of germ cells, the epithelium of the
genital ridges proliferates. Epithelial cells penetrate the underlying
mesenchyme & there they form a number of irregularly- shaped
cords, the ‘Primitive sex cords’.
If the embryo is genetically male (XY).
• Under the influence of the Y chromosome (encoding the
TDF), the primitive sex cords continue to proliferate &
penetrate deep into the ‘medulla’ to form the medullary
cords of Testis.
If the embryo is genetically female (XX).
• In the absence of Y chromosome, the medullary cords of
the indifferent gonad regress and a second generation of
cortical cords of Ovary develop.
Factor determining the differentiation of Gonads
Genital duct System in Indifferent Gonad stage
• Both male & female embryos
have initially two pairs of
genital ducts;
• Mesonephric (Wolffian’s)
ducts
• Paramesonephric
(Mullerian’s) ducts.
• Mesonephric Ducts: They are the medially located
ducts initially used by the developing kidneys (Mesonephros)
to drain urine into the cloaca. As the ‘mesonephros
degenerates, its duct on each side is used by the developing
‘Testis’
• Paramesonephric Ducts: They are located lateral to
the developing kidneys & mesonephric ducts. The open
cranial ends of these ducts are funnel-shaped. In case of a
female embryo, the two paramesonephric ducts will give rise
to female reproductive tract.
• In case of a male embryo,
• the ‘Sertoli cells’ of the developing Testes produce Mullerian-
Inhibiting-Factor/Substance (MIF/MIS) that causes the regression
of Paramesonephric duct system.
• In case of a female embryo,
• the Mesonephric duct system degenerates under the influence of
female hormones.
Appearance of Genitalia in an indifferent stage
In 3rd wk of IUL, mesenchymal cells migrate around the cloacal membrane to
form a pair of slightly elevated ‘cloacal folds’
Cranial to the cloacal membrane, the coacal folds unite to form the ‘Genital
tubercle’.
During the 6th wk, cloacal membrane divides into urogenital & anal membranes,
the cloacal folds also subdivide into an anterior pair, the urethral folds and a
posterior pair, the anal folds.
Genital swellings & their fate :
Later on, another pair of elevations,
the genital swellings, become visible
on each side of the urethral folds.
– In a male embryo, these swellings
later form ‘scrotal swellings’
– In a female embryo, they will form
the ‘labia majora’.
At the end of 6th wk, it is impossible
to distinguish between the two
sexes.
GT: Genital Tubercle
GS: Genital swelling
UF: Urethral Fold
AF: Anal Fold
SRY gene brings TDF with it
Early differentiation (male) at 7 weeks of IUL leading to
formation of medullary cords
1.Mesonephric duct (Wolff)
2.PGC
3.Peritoneal cavity
4.Aorta
5.Mesonephric tubule
6.Gonadal cords
7.Coelomic epithelium
8.Intestine
9.Mesentery
10Paramesonephric
duct (Müller)
11.Mesonephric nephron
• The testis cords loose contact with the surface
epithelium.
• They got separated from the surface epithelium by a
dense layer of fibrous connective tissue, the ‘Tunica
Albuginea’. (a characteristic feature of the testis).
Testicular cords growing into the medulla & appearance of
Tunica albuginea (at 7 wks of IUL)
1.Mesonephric duct (Wolff)
2. Mesonephric nephron
(atrophying)
3. Testicular cords surround the
PGC
4. Aorta
5. Paramesonephric duct (Müller)
6. Mesonephric tubule
7. Testicular cords that grow into
the medulla
8. Tunica albuginea
The testicular cords penetrate into medulla, branch within the
tunica albuginea, and form anastomoses among themselves and
with the mesonephric tubules, leading to the formation of rete
testis.
1.Mesonephric duct (Wolff)
2.Testicular cords, surround
the PGC
3.Aorta
4.Paramesonephric duct
(atrophying)
5.Mesonephric tubule
(later efferent ductules)
6.Testicular cords
7.Tunica albuginea
The deep portion of testicular cords form straight seminiferous tubules,
which converge to rete testis, from which - on the other side - the
efferent ductules (mesonephric tubules) depart. Finally, they empty into
the mesonephric duct (Wolff).
1.Mesonephric duct (Wolff)
2.PGC surrounded by supporting cells
(Sertoli)
3.Aorta
4.Paramesonephric duct
(degenerating)
5.Efferent ductules
6.Straight seminiferous tubule
7.Tunica albuginea
8.Convoluted seminiferous tubule
9.Rete testis (testicular network)
• In the 4th month of IUL, these cords become horseshoe-
shaped, and their extremities are continuous with those of
the ‘Rete testis’
• The cords are now composed of primitive germ cells &
‘sustentacular cells of Sertoli’.
differentiated testis in the 4th month
1.Ductus/Vas deferens
2. Epididymis
3. Efferent ductules
4. Appendix epididymidis
5. Appendix testis
6. Convoluted seminiferous tubules
7. Rete testis
8. Straight seminiferous tubules
9. Tunica albuginea
10.Paradidymis
11. Interlobular septum
12. Mesothelium
A. Lobule
Cellular population of Primitive Testes
• Primitive germ cells (Endodermal)
– Migrated from the wall of the yolk sac and arranged themselves in between the
cords of testes
– Multiply extensively and transform into spermatazoa throughout the life of an
individual
• Sustentacular cells of Sertoli (Mesodermal)
– Derived from the surface epithelium of the testes
– Responsible for the production of MIH during the fetal life
– Act like supporting cells of testes after birth
• Interstitial cells of Leydig (Mesodermal)
– derived from intermediate mesoderm of gonadal ridges
– Responsible for the production and release of Testosterone from the 8th wk of IUL
Descent of Testes & formation of
Inguinal canal
• During the 2nd month of IUL, both the testis and mesonephros
are attached to the posterior body wall by a urogenital
mesentery.
• As the mesonephros degenrates, this mesentery becomes a
ligamentous cord, the Gubernaculum.
• Its proximal portion attaches to the caudal pole of the testis.
While, its distal portion initially is attached near the
developing inguinal region.
• As the testis starts its descent towards the inguinal region, an
extra-abdominal portion of the Gubernaculum develops,
passes through the newly formed inguinal canal and attaches
its distal portion into the base of Scrotal skin.
At 2 months of IUL
1.Gubernaculum testis
2.Penis
3.Inguinal canal
4.Testis
5.Peritoneal cavity
6.Ductus deferens
The testes reach the level of deep inguinal ring
At 3 months of IUL
Pass through the inguinal canal along with the ductus deferens
At 7 months of IUL
The shrinking of gubernaculum will pull the testes further down
into the inguinal canal
At 9 months of IUL
The testes reach and settle down into the scrotal swelling
Section through the scrotum at the time of
birth showing the layers covering the Testis 1. Epidermis
2. Dermis (Dartos muscle)
3. External spermatic fascia
4. cremaster muscle
5. Internal spermatic fascia
6. Parietal layer of the tunica
vaginalis
7. Virtual cavity b/w the two
layers of the tunica vaginalis
8. Visceral layer of the tunica
vaginalis
9. Tunica albuginea
10. Interlobular septum of the
testis
Abdominal peritoneum related to the Testes
• An evagination of the abdominal peritoneum, the Processus vaginalis
follows the course of Gubernaculum through the inguinal ring into the
scrotal swellings along with the descending testis.
• As it passes through the canal, it partially surrounds the testis within the
scrotum. Here this layer is known as the ‘tunica vaginalis’.
Anomalies of Tunica vaginalis
Testicular Hydrocele
• Hydrocele is a fluid-filled cavity
of either testis or spermatic cord,
where peritoneal fluid passes
into a patent processus
vaginalis.
Undescended Testis / Cryptorchidism
• It is an abnormality of either unilateral or bilateral testicular
descent, occurring in up to 30% premature and 3-4% term males.
Descent may complete postnatally in the 1st year, failure to descend
can result in sterility.
• The types are classified on whether the testis is located in the
normal descent pathway (true) or in an abnormal location (ectopic).
MESONEPHRIC / WOLFFIAN DUCTS
• Male duct system
• Trigone of Bladder (in both sexes)
Male duct system
• Ductuli efferentes
• Epididymis
• Vas/Ductus deferens
• Seminal vesicles
• Ejaculatory ducts
Development of Accessory glands
Prostate
• Multiple endodermal outgrowths
arise from the prostatic part of
urethra and grow into the
surrounding mesenchyme.
glandular epithelium
differentiates from endodermal
cells.
dense stroma and smooth
muscle of Prostate
differentiates from associated
mesoderm.
Seminal vesicles
They are the glandular outgrowths
from the epithelium of Vas deferens
Formation of Male External Genitalia
Under the influence of
Testosterone, the genital tubercle
(GT) elongates rapidly to form
‘phallus’
The phallus pulls the urethral folds
(UF) forward & they form the
lateral walls of the urethral groove
(UG).
The UG extends along the caudal
part of the phallus, but does not
reach the most distal part (the
Glans penis).
Urethral
Plate
Formation of Penile Urethra
• At the end of 3rd month, the two
urethral folds close over the urethral
plate, thus forming a canal like
‘penile urethra’.
• This canal doesn’t extend to the tip
of phallus (glans).
• The most distal part/tip of urethra is
formed during the 4th month by the
invagination of ectoderm lining of
the glans
Therefore, the entire Penile urethra has an Endodermal lining, but
the tip of urethra is lined by Ectoderm
Development of Scrotal sacs
• The genital/ scrotal swellings are
initially located in the inguinal
region.
• With further development they
move caudally, and each swelling
makes up half of the scrotum.
• The two halves are separated
from each other by a midline
scrotal septum, creating two sacs
for the two testes.
Congenital malformations of the Male Urethra
Hypospadias:
• When the fusion of urethral folds is
incomplete.
• Abnormal openings of the urethra
may be found along the inferior
aspect of the penis (Phallus).
• Most frequently, the abnormal
orifices are near the glans, along
the shaft, or near the base of the
penis.
Epispadias:
• In this abnormality, the urethral
meatus is found on the dorsum of
the penis.

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Development of the male reproductive system

  • 1. DEVELOPMENT OF THE MALE REPRODUCTIVE SYSTEM Dr. Sahar Hafeez – MD drsaharhafeez@yahoo.com 2016
  • 2. LEARNING OBJECTIVES The students should be able to; • Briefly describe the process of the arrival of Primordial germ cells with in the genital ridges • Discuss the formation of the ‘primitive sex cords’ • Discuss the significance and role of SRY gene in the development of gonads • Enumerate the genital duct systems existing in the ‘indifferent gonad stage’. • Discuss in detail, the differentiation of Testes and the male duct system. • Briefly discuss the most common congenital malformations of the male reproductive tract • Briefly discuss the differentiation & malformations of external genitalia in males.
  • 3. INTERMEDIATE MESODERM 1. Paraxial mesoderm 2. Splanchnopleuric mesoderm 4. Somatopleuric mesoderm 5. Intermediate mesoderm 3. Gut Endoderm 6. Notocord 7. Extra embryonic cavity 8. Dorsal Aortae 9. Neural tube The Main source of origin is ;
  • 4. • The kidneys, ureters and Reproductive system develop from Intermediate mesoderm. • Urinary bladder and urethra develop from gut endoderm (the urogenital sinus)
  • 5. The beginning • In the 3rd wk of IUL, primordial germ cells (PGC) appear along with the endodermal cells in the wall of yolk sac close to the dorsal mesentery of hind gut. • They arrive near the genital ridges at the beginning of the 5th week and invade the ridges in the 6th week of development. Migration of PGC from yolk sac to the gonadal ridges takes place b/w the 4 – 6 wks of IUL
  • 6. Anatomic relationship between the genital and urinary systems 1. Coelomic epithelium 2. Intermediate mesoderm (in proliferation) 3. Gonadal cord 4. Primordial germ cells (PGC) 5. Mesenchyme 6. Allantois 7. Vitelline duct 8. Intestine 9. Dorsal mesentery 10. Genital ridge 11. Nephrogenic cord 12. Mesonephric duct (Wolff) 13. Mesonephric tubule 14. Aorta
  • 7. • Although, the sex of the embryo both chromosomally & genetically is established at the very first day of conception (at the time of fertilization), the developing gonads stay in an indifferent state till the 7th wk of IUL
  • 8. • Shortly before the arrival of germ cells, the epithelium of the genital ridges proliferates. Epithelial cells penetrate the underlying mesenchyme & there they form a number of irregularly- shaped cords, the ‘Primitive sex cords’.
  • 9. If the embryo is genetically male (XY). • Under the influence of the Y chromosome (encoding the TDF), the primitive sex cords continue to proliferate & penetrate deep into the ‘medulla’ to form the medullary cords of Testis. If the embryo is genetically female (XX). • In the absence of Y chromosome, the medullary cords of the indifferent gonad regress and a second generation of cortical cords of Ovary develop. Factor determining the differentiation of Gonads
  • 10.
  • 11. Genital duct System in Indifferent Gonad stage • Both male & female embryos have initially two pairs of genital ducts; • Mesonephric (Wolffian’s) ducts • Paramesonephric (Mullerian’s) ducts.
  • 12. • Mesonephric Ducts: They are the medially located ducts initially used by the developing kidneys (Mesonephros) to drain urine into the cloaca. As the ‘mesonephros degenerates, its duct on each side is used by the developing ‘Testis’ • Paramesonephric Ducts: They are located lateral to the developing kidneys & mesonephric ducts. The open cranial ends of these ducts are funnel-shaped. In case of a female embryo, the two paramesonephric ducts will give rise to female reproductive tract.
  • 13. • In case of a male embryo, • the ‘Sertoli cells’ of the developing Testes produce Mullerian- Inhibiting-Factor/Substance (MIF/MIS) that causes the regression of Paramesonephric duct system. • In case of a female embryo, • the Mesonephric duct system degenerates under the influence of female hormones.
  • 14. Appearance of Genitalia in an indifferent stage In 3rd wk of IUL, mesenchymal cells migrate around the cloacal membrane to form a pair of slightly elevated ‘cloacal folds’ Cranial to the cloacal membrane, the coacal folds unite to form the ‘Genital tubercle’. During the 6th wk, cloacal membrane divides into urogenital & anal membranes, the cloacal folds also subdivide into an anterior pair, the urethral folds and a posterior pair, the anal folds.
  • 15. Genital swellings & their fate : Later on, another pair of elevations, the genital swellings, become visible on each side of the urethral folds. – In a male embryo, these swellings later form ‘scrotal swellings’ – In a female embryo, they will form the ‘labia majora’. At the end of 6th wk, it is impossible to distinguish between the two sexes. GT: Genital Tubercle GS: Genital swelling UF: Urethral Fold AF: Anal Fold
  • 16. SRY gene brings TDF with it
  • 17. Early differentiation (male) at 7 weeks of IUL leading to formation of medullary cords 1.Mesonephric duct (Wolff) 2.PGC 3.Peritoneal cavity 4.Aorta 5.Mesonephric tubule 6.Gonadal cords 7.Coelomic epithelium 8.Intestine 9.Mesentery 10Paramesonephric duct (Müller) 11.Mesonephric nephron
  • 18. • The testis cords loose contact with the surface epithelium. • They got separated from the surface epithelium by a dense layer of fibrous connective tissue, the ‘Tunica Albuginea’. (a characteristic feature of the testis).
  • 19. Testicular cords growing into the medulla & appearance of Tunica albuginea (at 7 wks of IUL) 1.Mesonephric duct (Wolff) 2. Mesonephric nephron (atrophying) 3. Testicular cords surround the PGC 4. Aorta 5. Paramesonephric duct (Müller) 6. Mesonephric tubule 7. Testicular cords that grow into the medulla 8. Tunica albuginea
  • 20. The testicular cords penetrate into medulla, branch within the tunica albuginea, and form anastomoses among themselves and with the mesonephric tubules, leading to the formation of rete testis. 1.Mesonephric duct (Wolff) 2.Testicular cords, surround the PGC 3.Aorta 4.Paramesonephric duct (atrophying) 5.Mesonephric tubule (later efferent ductules) 6.Testicular cords 7.Tunica albuginea
  • 21. The deep portion of testicular cords form straight seminiferous tubules, which converge to rete testis, from which - on the other side - the efferent ductules (mesonephric tubules) depart. Finally, they empty into the mesonephric duct (Wolff). 1.Mesonephric duct (Wolff) 2.PGC surrounded by supporting cells (Sertoli) 3.Aorta 4.Paramesonephric duct (degenerating) 5.Efferent ductules 6.Straight seminiferous tubule 7.Tunica albuginea 8.Convoluted seminiferous tubule 9.Rete testis (testicular network)
  • 22. • In the 4th month of IUL, these cords become horseshoe- shaped, and their extremities are continuous with those of the ‘Rete testis’ • The cords are now composed of primitive germ cells & ‘sustentacular cells of Sertoli’.
  • 23. differentiated testis in the 4th month 1.Ductus/Vas deferens 2. Epididymis 3. Efferent ductules 4. Appendix epididymidis 5. Appendix testis 6. Convoluted seminiferous tubules 7. Rete testis 8. Straight seminiferous tubules 9. Tunica albuginea 10.Paradidymis 11. Interlobular septum 12. Mesothelium A. Lobule
  • 24. Cellular population of Primitive Testes • Primitive germ cells (Endodermal) – Migrated from the wall of the yolk sac and arranged themselves in between the cords of testes – Multiply extensively and transform into spermatazoa throughout the life of an individual • Sustentacular cells of Sertoli (Mesodermal) – Derived from the surface epithelium of the testes – Responsible for the production of MIH during the fetal life – Act like supporting cells of testes after birth • Interstitial cells of Leydig (Mesodermal) – derived from intermediate mesoderm of gonadal ridges – Responsible for the production and release of Testosterone from the 8th wk of IUL
  • 25. Descent of Testes & formation of Inguinal canal
  • 26. • During the 2nd month of IUL, both the testis and mesonephros are attached to the posterior body wall by a urogenital mesentery. • As the mesonephros degenrates, this mesentery becomes a ligamentous cord, the Gubernaculum. • Its proximal portion attaches to the caudal pole of the testis. While, its distal portion initially is attached near the developing inguinal region. • As the testis starts its descent towards the inguinal region, an extra-abdominal portion of the Gubernaculum develops, passes through the newly formed inguinal canal and attaches its distal portion into the base of Scrotal skin.
  • 27. At 2 months of IUL 1.Gubernaculum testis 2.Penis 3.Inguinal canal 4.Testis 5.Peritoneal cavity 6.Ductus deferens The testes reach the level of deep inguinal ring
  • 28. At 3 months of IUL Pass through the inguinal canal along with the ductus deferens
  • 29. At 7 months of IUL The shrinking of gubernaculum will pull the testes further down into the inguinal canal
  • 30. At 9 months of IUL The testes reach and settle down into the scrotal swelling
  • 31. Section through the scrotum at the time of birth showing the layers covering the Testis 1. Epidermis 2. Dermis (Dartos muscle) 3. External spermatic fascia 4. cremaster muscle 5. Internal spermatic fascia 6. Parietal layer of the tunica vaginalis 7. Virtual cavity b/w the two layers of the tunica vaginalis 8. Visceral layer of the tunica vaginalis 9. Tunica albuginea 10. Interlobular septum of the testis
  • 32. Abdominal peritoneum related to the Testes • An evagination of the abdominal peritoneum, the Processus vaginalis follows the course of Gubernaculum through the inguinal ring into the scrotal swellings along with the descending testis. • As it passes through the canal, it partially surrounds the testis within the scrotum. Here this layer is known as the ‘tunica vaginalis’.
  • 33. Anomalies of Tunica vaginalis
  • 34. Testicular Hydrocele • Hydrocele is a fluid-filled cavity of either testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
  • 35. Undescended Testis / Cryptorchidism • It is an abnormality of either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males. Descent may complete postnatally in the 1st year, failure to descend can result in sterility. • The types are classified on whether the testis is located in the normal descent pathway (true) or in an abnormal location (ectopic).
  • 36. MESONEPHRIC / WOLFFIAN DUCTS • Male duct system • Trigone of Bladder (in both sexes)
  • 37. Male duct system • Ductuli efferentes • Epididymis • Vas/Ductus deferens • Seminal vesicles • Ejaculatory ducts
  • 38. Development of Accessory glands Prostate • Multiple endodermal outgrowths arise from the prostatic part of urethra and grow into the surrounding mesenchyme. glandular epithelium differentiates from endodermal cells. dense stroma and smooth muscle of Prostate differentiates from associated mesoderm. Seminal vesicles They are the glandular outgrowths from the epithelium of Vas deferens
  • 39. Formation of Male External Genitalia Under the influence of Testosterone, the genital tubercle (GT) elongates rapidly to form ‘phallus’ The phallus pulls the urethral folds (UF) forward & they form the lateral walls of the urethral groove (UG). The UG extends along the caudal part of the phallus, but does not reach the most distal part (the Glans penis). Urethral Plate
  • 40. Formation of Penile Urethra • At the end of 3rd month, the two urethral folds close over the urethral plate, thus forming a canal like ‘penile urethra’. • This canal doesn’t extend to the tip of phallus (glans). • The most distal part/tip of urethra is formed during the 4th month by the invagination of ectoderm lining of the glans Therefore, the entire Penile urethra has an Endodermal lining, but the tip of urethra is lined by Ectoderm
  • 41. Development of Scrotal sacs • The genital/ scrotal swellings are initially located in the inguinal region. • With further development they move caudally, and each swelling makes up half of the scrotum. • The two halves are separated from each other by a midline scrotal septum, creating two sacs for the two testes.
  • 42. Congenital malformations of the Male Urethra Hypospadias: • When the fusion of urethral folds is incomplete. • Abnormal openings of the urethra may be found along the inferior aspect of the penis (Phallus). • Most frequently, the abnormal orifices are near the glans, along the shaft, or near the base of the penis. Epispadias: • In this abnormality, the urethral meatus is found on the dorsum of the penis.