This lecture encompasses the pertinent structural details of the sequence of embryological development of the male and female reproductive tracts. Focusing over the detail of differentiation of gonadal ridges into male & female gonads and development of the duct systems in both sexes during the first few weeks intrauterine life.
2. LEARNING OBJECTIVES
The students should be able to;
• Briefly describe the process of arrival of the 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’.
• Briefly discuss the role of male & female hormones in the
differentiation of the ducts system
4. • Both the Urinary & Genital systems develop from the
Intermediate mesoderm.
• A ‘Urogenital ridge’ is formed on each side of the Aorta
along the dorsal body wall of the embryo.
• The smaller medially facing region is known as the
‘Gonadal ridge’, while, the laterally placed region is the
‘urinary ridge’
Urinary bladder and urethra develop from the
gut endoderm (urogenital sinus)
6. Close 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. Origin & migration of Primordial germ cells
• In the beginning of 4th wk of IUL, the primordial germ cells
(PGC) appear along with the endodermal cells in the wall of
the yolk sac close to the dorsal mesentery of the hind gut.
Migration of the PGC from yolk sac to gonadal ridges (4th – 6th Week)
• 1. PGC
• 2. Allantois
• 3. Cloacal membrane
• 4. Epiblast
• 5. Pharyngeal
membrane
• 6. Heart tube
• 7. Yolk sac
• 8. Endoderm
• 9. Mesoderm
8. • PGC arrive near the genital ridges at the beginning of the 5th
week and invade the ridges in the 6th week of development.
Failure of arrival of PGC in the Gonadal ridges ------ gonads DONOT develop.
9. Formation of Primitive sex cords
• Shortly before the arrival of germ cells, the epithelium of
genital ridges proliferates. Epithelial cells penetrate the
underlying mesenchyme & form a number of irregularly-
shaped cords, the ‘Primitive sex cords’.
The indifferent gonad consists of an outer cortex & an inner medulla
11. • 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
12. Factor determining the differentiation of Gonads
If the embryo is genetically male (XY).
• Under the influence of the Y chromosome (encoding the Testis-
Determining Factor TDF), the primitive sex cords continue to
proliferate & penetrate deep into the ‘medulla’ of indifferent
gonad 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.
13.
14. 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.
Differentiation of these duct systems & external genitalia depends
upon the nature of circulating hormones in the fetus
15. • 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.
16. • In case of a male embryo, the ‘Sertoli cells’ of the developing
Testes produce a non-steroidal substance, the Mullerian-
Inhibiting-Factor/Substance (MIF/MIS). It causes the regression
of the Paramesonephric duct system.
• While, under the influence of produced Testosterone the
indifferent genital tubercle takes the shape of male external
genitalia.
• In case of a female embryo, the Mesonephric duct system
degenerates under the influence of female hormones.
• While, the indifferent genital tubercle transforms into the female
external genitalia under the influence of circulating Estrogen.
17.
18. 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 folds unite to
form the ‘Genital tubercle’.
During the 6th wk, with the
division of cloacal membrane
into urogenital & anal
membranes, the cloacal folds
also subdivide into an anterior
pair, the urethral folds and a
posterior pair, the anal folds.
19. Fate of Genital swellings
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
20. Development of the Male Reproductive system
Learning Objectives
• Briefly describe the step by step process of testicular
development.
• Discuss the origins and roles of each cell type present in
the developing testis.
• Describe the normal descent of testes elaborating upon
the role of ‘gubernaculum’.
• Briefly discuss the congenital malformations related to
the descent.
• Briefly discuss the development of Prostate gland &
Seminal vesicles
• Describe the process of formation of male urethra &
congenital malformations related to it.
21. Development of the Male Reproductive system
• SRY gene brings TDF with it
(Sex-determining Region on Y, located on the short limb
of Y chromosome)
22. 1.Mesonephric duct (Wolff)
2.PGC
3.Peritoneal cavity
4.Aorta
5.Mesonephric tubule
6.Gonadal cords
7.Coelomic epithelium
8.Intestine
9.Mesentery
10 Paramesonephric
duct (Müller)
11.Mesonephric nephron
TDF secreted by the male primordial
germ cells leads to the formation of
Medullary cords with in the
indifferent gonads during the 7 wk of
IUL
23. Appearance of Tunica Albuginea
• The testicular 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).
In case of male gonads, the cortex regresses.
24. 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
25. The testicular cords penetrate into the medulla, branch within
the tunica albuginea, and form anastomoses among themselves
and with the mesonephric tubules, leading to the formation of
the 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
26. The deep portion of the testicular cords form the straight
tubules, which converge to the rete testis. Tunica albuginea
sends septae to divide the testis into multiple lobules.
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)
27. • In the 4th month of IUL,the cords become horseshoe-
shaped & are composed of primitive germ cells &
‘sustentacular cells of Sertoli’.
The cords remain solid until puberty. Once they acquire a lumen they are
known as ‘seminiferous tubules’.
29. Cellular population of Primitive Testes
• PRIMITIVE GERM CELLS (endodermal)
▫ Originate & migrate from the wall of the yolk sac .
▫ Production of spermatocytes throughout the life of an individual
• SUSTENTACULAR CELLS OF SERTOLI (mesodermal)
▫ Derived from the surface epithelium of the testes
▫ Responsible for the production & release 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
31. • 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.
32. At 2 months of IUL
1.Gubernaculum testis
2.Penis
3.Inguinal canal
4.Testis
5.Peritoneal cavity
6.Ductus deferens
33. At 3 months of IUL
Passing through the inguinal canal along with
the ductus deferens
34. At 7 months of IUL
The shrinking of gubernaculum will pull the
testes further down into the inguinal canal
35. At 9 months of IUL
The testis reaches and settles down into the scrotal swelling
36. 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
37. 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’.
38. Congenital Malformations
• Congenital Inguinal Hernia: Normally, the connection
b/w the coelomic cavity & the processus vaginalis closes in the
1st year of life. If this passageway remains open, intestinal
loops may descend into the scrotum, causing an ‘inguinal
hernia’ .
• Hydrocele: Sometimes this passageway is irregularly closed,
leaving small cyst along its course. Later this cyst may secrete
excess fluid, resulting in the formation of a hydrocele in the
scrotal sac.
40. Cryptorchism/Undescended
Testis:
• At about the time of birth, the
Testes arrive in the scrotum . In
some cases, one or both of the
testes may remain in the pelvic
cavity or stuck somewhere in the
inguinal canal until puberty and
then descend. Or, sometimes they
remain in that abnormal position
for an indefinite time.
• This undescended testis is unable to
produce mature spermatozoa,
probably due to a high temprature
of the abdominal cavity.
Orchiopexy is a surgical procedure to rectify this condition
42. Male duct system
• Ductuli
efferentes
• Epididymis
• Vas/Ductus
deferens
• Seminal vesicles
• Ejaculatory
ducts
43. 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
The Seminal vesicles are the
glandular outgrowths from the
epithelium of Vas deferens
44. 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
45. 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
46. 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.
47. 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.
48.
49. Development of the Female Reproductive system
• Learning Objectives
• Discuss the process of differentiation of the indifferent gonad into Ovaries
and source of origin of the elements of ovarian follicles.
• Briefly describe the descent of Ovaries and formation of the ‘round
ligaments of ovary & uterus’.
• Describe the formation of different parts of the female tract by the
paramesonephric/Mullerian ducts.
• Discuss the formation of ‘broad ligament’
• Discuss the common congenital malformations of the Uterus
• Briefly describe the formation of Vagina and related malformations .
• Discuss the formation of female external genitalia
50. • Absence of SRY gene
• No TDF
• Development of ovaries
• female duct system
51. Formation of the Secondary Cortical cords
• The surface epithelium continues
to proliferate. In the 7th wk, it
gives rise to a second generation
of ‘cortical cords’.
• In the 4th month of IUL, these
cords split into isolated cell
clusters, each surrounding one or
more primitive germ cells.
• The germ cells develop into
‘oogonia’.
• The surrounding surface
epithelial cells form the ‘follicular
cells’.
52. Degeneration of the medullary sex cords &
development of cortex
1. Mesonephric duct (Wolff)
2. PGC
3. Peritoneal cavity
4. Aorta
5. Mesonephric tubule
6. Degenerated gonadal cords
7. Thickened Coelomic
epithelium
8. Intestine
9. Mesentery
10. Paramesonephric duct
(Müller)
11. Atrophy of mesonephric
nephron
53. 1.Mesonephric duct (Wolff)
atrophying
2.Primordial follicle in the
ovarian cortex containing
primary Oocyte
3.Aorta
4.Paramesonephric duct (Müller)
5.Mesonephric tubules atrophying
6.Degenerated Gonadal cords
7.Mesothelium of the ovary
54. • Number of Primary Oocytes at 20 wks of IUL
• 7 million
• Number of Primary Oocytes at Puberty
• 400,000
55. Descent of ovaries & the fate of Gubernaculum
The ovaries are also pulled down
from the lumbar region to the
Pelvic cavity.
They settle down slightly below
the level of pelvic brim.
Cranial end of Gubernaculum
attached b/w the lower pole of
ovary & side of uterus becomes
the ‘round ligament of ovary’.
While, the portion crossing the
sides of uterus till the caudal end
attached on the Labia majora
becomes the ‘round ligament
of uterus’
56. Development of the Uterus & Fallopian tubes
PARAMESONEPHRIC / MULLERIAN DUCTS
• Fallopian tubes
• Uterus
Fundus
Body
Cervix
Vaginal fornices
57. Parts of the Paramesonephric ducts
Initially three parts of the Paramesonephric duct are
recognizable;
• Cranial vertical part which opens with in the
coelomic cavity.
• Mid horizontal part which crosses the mesonephric
duct.
• Caudal vertical part which fuses in the midline with
its partner from the opposite side.
58. Formation of the uterus (7th – 8th wks of IUL)
1a. Paramesonephric duct (Müller), 2a. Mesonephric duct (Wolff)
3a. Lower gubernaculum, 4a. Utero-vaginal canal, 5a. Urogenital sinus
59. Formation of the Fallopian tubes & Uterus
• With the descent of ovaries into the pelvic inlet, the first
two parts of the duct on each side will develop into the
Fallopian/Uterine tube.
• The caudal fused parts will become the Uterine canal.
• The fused paramesonephric ducts will give rise to the
fundus, body, and cervix of the uterus as well as the
upper part of the vagina.
• The surrounding mesenchyme will form the
‘myometrium’ & ‘perimetrium’.
61. • As the 2 paramesonephric ducts fuse in the midline, a broad transverse
peritoneal fold establishes on each side, the Broad Ligament.
• Each ligament extends from the side of the uterus towards Pelvic walls .
• The Fallopian tubes are located in the upper border of each ligament & the
ovary lies behind it.
Formation of Broad Ligament of Uterus
62. Congenital malformations of the Uterus
Lack of fusion of Paramesonephric ducts in a localized
area or throughout the length results in different types
of duplication of uterus.
• Uterus didelphys results from failure of fusion of the inferior
parts of paramesonephric ducts. The uterus is entirely double and
each one enters a separate vagina .
• Uterus arcuatus is the least severe form in which there is
malfusion in the upper region of the vertical parts of
paramesonephric ducts & is represented by a slight indentation in
the middle of the fundus of uterus.
• Uterus bicornis is one of the more common anomalies in which
the malfusion involves only the superior part of the
paramesonephric ducts resulting in a double-horned uterus
entering a single vagina.
64. Development of the Vagina
(during 7th wk of IUL)
• The solid tip of fused paramesonephric ducts reaches the
dilated pelvic part of UG sinus.
• This solid part of UG sinus is known as ‘sinovaginal bulb’ or
vaginal plate
• The plate keeps on proliferating (thus increasing the
distance b/w the uterus & UG sinus).
• Four wing-like expansions of the fused paramesonephric
duct will encircle the cranial part of the vaginal plate. They
will become the ‘vaginal fornices’.
65.
66. Canalization of the Vagina & formation of Hymen
• The central cells of the vaginal plate break down (by the
process of apoptosis) and a canal is formed which is
continuous cranially with the uterine canal.
• But, caudally it is separated from the cavity of the UG sinus
by a transverse membrane, the ‘hymen’ which is formed by
the invagination of the posterior wall of UG sinus.
• At the time of birth (perinatal period), this hymen usually
ruptures in the middle & remains as a thin fold of mucous
membrane just within the vaginal orifice.
67. Uterine canal & Vagina (at the time of birth)
2.Vaginal vestibule
3a. Uterine cavity
3b. Uterine cervix (neck)
6a. Vagina: The lower fourth
out of endoderm
6b. Vagina: The upper 3/4 out
of mesoderm
9. Hymen
68. Anomalies of the Vagina
• Vaginal Atresia: Failure of
canalization of the vaginal
plate will lead to vaginal
atresia.
• Imperforated hymen:
• If the middle portion of the
hymen fails to get thin down
during the last weeks of IUL,
there would be failure of
rupture of hymen during the
time of birth resulting in an
imperforate hymen.
69. Formation of Female external genitalia
• The genital tubercle (GT)
elongates only slightly and
forms the clitoris
• The urethral folds (UF) do not
fuse and develop into Labia
minora.
• The genital swellings enlarge
greatly and form the labia
majora.
• The urogenital groove is open
to the surface & forms the
vestibule of vagina.