THE DEVELOPMENT OF THE UROGENITAL

SYSTEM
• AIM OF THE LECTURE

• At the end of this lecture, students should be able to:

1. Describe how the gonads are formed
2. Explain how the sex of the embryo is determined
3. Describe the development of the Testes and ovaries
4. Describe the development of the Internal and External
genitalia in both male and female
5. List and explain the different anomalies in the development of
the female and male reproductive systems
INTRODUCTION
• The urinary and Genital or Reproductive system are closely related.
They both originate from the intermediate mesoderm located along
the posterior wall of the abdominal cavity and form the urogenital
system

• The urogenital system plays an excretory role in the early embryo and
the ducts of the two component systems open into the cloaca. The
genital system, however loses its excretory role in later embryonic
life and develops into a separate system for reproduction
 THE GENITAL SYSTEM
• The genital system consist of the male and female
reproductive systems
• Gonads
• Sex determination
• Testes
• Ovary
• Internal genitalia
• External genitalia
• Clinical implications
GONADS
• The genetical sex of an embryo is determined at
fertilization. However, the morphological character
of the gonads is acquired only after the end of 6
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week of embryo development

• Hence the development of the genital system before
the 7 week is regarded as indifferent stage, because
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the reproductive system of both sexes are

indistinguishable
• The gonads begins as genital ridges derived from
the intermediate mesoderm and the overlying
epithelium and arise on the ventromedial surface of
the mesonephros as a pair of longitudinal ridges.
• The gonads at this stage do not contain germ cells
Diagram showing the relation of genital
Ridge to the mesonephros (Adapted from T. W.
sadler)
Gonads continue
• During the 4 week of development, the primordial germ
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cells are formed among the endodermal cells of the

trilaminar embryo, in the wall of the yolk sack close to the
allantois
• They migrate along the dorsal mesentery of the hindgut. By
the beginning of the 5 week, they arrived at the primitive
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gonads and during the 6 week invade the genital ridges

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• Proliferation of the epithelium of the genital ridges and

subsequent penetration of these epithelial cells into the
underlying mesenchyme results in the formation of
Primitive sex cords
• These primitive sex cords are indistinguishable in both
sexes, hence the gonads are known as indifferent (i.e a
combination of the germ cells and primitive sex cords =
Indifferent gonads)
The site of the origin of the primordial germ cells
and their partway of migration (Adapted from T. W. Sadler)
SEX DETERMINATION
• The mammalian embryo is dimorphic (it comes in two sexes
-male and female). The key to this dimorphism is the Y
chromosome
• The Y chromosome contains a SRY (Sex-determining region
on Y) gene on its short (P) arm. It is this SRY gene that
determines if a gonad will develop into ovary or testis
• If genetically, an embryo is a male, the primordial germ cells
have XY sex chromosomes, but morphologically
unrecognised. However, if the Y-Chromosome of the
embryo contains the SRY gene, then the primitive gonad
develops into testis
• If on the other hand, the embryo is genetically a female, its
primordial germ cells will contain XX sex chromosomes and
in the absence of SRY gene, the gonad develops into ovary
TESTIS
• In the male the presence of the SRY gene induces the
primitive sex cords to proliferate and penetrate deep into
the medulla of the gonads to form Testis (Medullary) Cords
• Toward the hilum, the testis cords break into a network of
tiny cell strands that later form the tubules of the Rete testis
• As the embryo develops further, a dense fibrous layer of
connective tissue known as Tunica albuginea appears
between the testis cords and the surface epithelium
• At around the 16 week of embryonic development, the
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shape of the testis cords becomes horse-shoe shaped and

the cords become joined to the excretory tubules of the rete
testis. At this time, the cords are made up of the primitive
germ cells and the Sertoli cells which are support cells
Images showing Testes and genital ducts @ 4
months with cords of the Horse-shoe testes
joined to the rente testes (Adapted from T.W. Sadler)
Testis continue
• In between the testis cords, Leydig cells derived from the
original mesenchyme of the gonadal ridge develop along
w it h t h e t e st is c ord s. T h e ir d ev e lop me n t ac t u ally
commence shortly after the onset of the differentiation of
the testis cords
• B y t h e 8 w e e k , t h e L e yd i g c e l l s st ar t t o p ro d u c e
t h

testosterone. The testosterone enable the testis induce

sexual differentiation of the internal and external genitalia in
the male
• It is to be noted that until puberty, the testis cords have no
lumen. It is only at puberty that they become canalized to
form the seminiferous tubules
• The seminiferous tubules then join the tubules of the rete
t est es w h ic h in t u rn join t h e efferen t du c t s of t h e
mesonephric (Wolf fia n) duct that later forms the Vas
deferens
OVARY
• In the female embryo, the XX sex chromosomes are present. Since
there is no Y chromosome, the SRY gene is absent, hence the
primitive sex cords dissociate into clusters which contain groups of
primitive germ cells and occupy the medulla of the ovary
• During further development these clusters disappear and are
replaced by a vascular stroma to form the ovarian Medulla
• Unlike male, in the female the surface epithelium of the gonad
continues to proliferate and by the 7tweek of embryonic life ,it gives
rise into a second generation of cords known as Cortical cords.
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These cortical cords penetrate the underlying mesenchyme, but

remain close to the surface
• During the 16tweek of embryonic life, the cortical cords break into
cell clusters with each surrounding one or more primitive germ cells
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• The germ cells then develop into Oogonia, while the surrounding
epithelial cells which originate from the surface epithelium form
follicular cells. The Oogonia together with the follicular cells form the
primordial follicle
Image showing ovary and genital ducts at7weeks & 5 months
with degenerating medullary cords (Adapted from T.W. Sadler)
Image showing ovary and genital ducts at 5
months with degenerating medullary cords
(Adapted from T.W. Sadler)
INTERNAL GENITALIA (GENITAL DUCTS)
INDIFFERENT STAGE
• In the first weeks of embryonic life, all embryos have
two pairs of genital ducts – the Mesonephric (Wolffian)
duct and paramesonephric (Müllerian) duct
• The paramesonephric ( müllerian) ducts arises as a
longitudinal invagination of the epithelium of the
urogenital ridge and opens into the abdominal cavity
cranially. It then runs lateral to the mesonephric duct
caudally and cross it ventrally towards the midline,
where it comes in close contact with the similar duct on
the opposite side
• The two ducts are initially separated by a septum, but
later fuse to form the uterine canal
Indifferent stage of the development of the
internal genitalia (adapted from Linda J. Heffner)
Development of the female internal genital ducts
(adapted from T. W. Sadler)
Internal genitalia (indifferent stage) continues
• A projection of the fused paramesonephric ducts into the urogenital
sinus forms a swelling known as Müllerian tubercle

MALE INTERNAL GENITALIA

• The presence of testosterone secreted by the Leydig cells induces the
mesonephric duct to differentiate into ductus deferens (Vas deferens),
epididymis and the opening of the urogenital sinus of the male
• At the same time, the presence of anti-müllerian hormone (AMH)
secreted by Sertoli cell causes the paramesonephric duct to degenerate
• As the mesonephric duct regresses, a few excretory tubules develop and
establish contact with the cords of the rete testis to form the Efferent
ducts
• Just below the entrance of the efferent ducts, the mesonephric duct
becomes elongated and convoluted to form the Epididymis and after the
epididymis the mesonephric duct differentiates into the Vas deferens
which extends to where the seminal vesicles grow out. The part of the
mesonephric duct below the seminal vesicles becomes the Ejaculatory
duct
IMAGE SHOWING THE DIFFERENTIATION OF
THE MESONEPHRIC DUCT (Adapted from T.
W. Sadler)
FEMALE INTERNAL GENITALIA
• In the female, the absence of Leydig cells means there
is no testosterone. This causes the mesonephric duct
to degenerate.
• On the other hand, the absence of AMH enables the
paramesonephric duct to differentiate and develop. The
first 2/3 portion develops into the fallopian tube
(Oviduct), while the caudal portion fuses with similar
part on opposite side to form the Uterus, Cervix and
upper 1/3 of the Vagina
• After the two paramesonephric ducts fused at the
midline, a broad transverse pelvic fold that extends
from the midline to the pelvic wall is established to
form the broad ligament of the uterus
Diagram showing differentiated paramesonephric
ducts into its component (Adapted from Linda J. Heffner)
IMAGE SHOWING FORMATION OF THE BROAD
LIGAMENT OF THE UTERUS (Adapted from T.W.
Sadler)
 THE DEVELOPMENT OF THE VAGINA
• As the solid tip of the paramesonephric duct reaches the
urogenital sinus, 2 solid evaginations known as Sinovaginal
bulbs grow out of the pelvic part of the sinus
• These sinoviginal bulbs proliferate to form a solid vaginal plate
which is the primordium for the last 2/3 part of the vagina
• By the 20 week of development, the whole vaginal plate
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becomes canalized
• The vaginal fornices, which are the wing-like expansions of the
vagina around the end of the uterus originate from the
paramesonephric ducts
• Hence, the vagina has a dual origin – the upper part from the
uterine canal and lower part from the urogenital sinus
• The lumen of the vagina remains separated from that of the
urogenital sinus by a thin tissue – Hymen. It usually develops a
small opening during the perinatal period of life
IMAGES SHOWING DEVELOPMENT OF THE
UTERUS AND VAGINA (Adapted from T. W. Sadler)
Sagittal section showing formation of the uterus
and vagina (Adapted from T.W. Sadler)
EXTERNAL GENITALIA
INDIFFERENT STAGE
• Sexual differentiation of the external genitalia begins in the 9
week of embryonic development and is completed by week 12 and
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started as indifferent stage (i.e cannot differentiate male from

female)
• It begins with the migration of mesenchyme cells from the region
of the primitive streak to the cloacal membrane in the 3 week of
embryonic life, resulting in the formation of a pair of cloacal folds
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• The cloacal folds then fuse cranially and ventrally to form genital
tubercle.
• Below the genital tubercle, the cloacal folds are subdivided into a
pair of urethral folds anteriorly and anal folds posteriorly
• Arising on each side of the urethral fold is a pair of swelling refer
to as genital swellings which later develop into scrotal swellings
in the male and Labia Majora in the female
• During this period (b/4 the 7 week), both sexes cannot be
distinguished as male or female
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Indifferent stage of development of external
genitalia (Adapted from T. W. Sadler)
Differentiation of the male external genitalia
• The development of the indifferent genitalia into the male
external genitalia is induced by the presence of
dihydrotestosterone (DHT) - a derivative of testosterone
• The genital tubercle first elongate to become the
primordial phallus
• Under the influence of DHT, the primordial phallus further
elongate to form the penis, while during the 3rd month, the
urethral folds fuse to form the penile urethra whose canal
end below the tip of the penis – the Glans penis
• Later in the 4th month, ectodermal cells from the glans
penetrate inward to form a short cord which become
canalised to form the external urethral meatus
IMAGES SHOWING DIFFERENTIATION OF THE
MALE EXTERNAL GENITALIA (Adapted from
T.W.Sadler)
Differentiation of the female external
genitalia
• In the female, Oestrogen secreted by the ovaries drives
the development of the external genitalia from the
indifferent genitalia
• In the female, the genital tubercle elongate only slightly to
form the Clitoris. Also, the urethral folds in the female do
not fuse, instead develop to form a pair of Labia minora
• As the phallus is formed, the urethral folds are pulled
forward to form the urethral groove. This groove remains
open forming the vestibule into which the female urethra
and vagina open
DESCENT OF THE TESTES
• As the testes are formed, by the 2 month of development,
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they are attached to the posterior wall of the abdomen by a

mesentery
• A mesenchymal condensation known as Gubernaculum
originates from the caudal pole of the testes and extends to
the inguinal region
• When the testes start descending, additional portion of the
gubernaculum is formed and extend to the scrotum
• The testes is pulled downward by the gubernaculum ,
through the inguinal canal into the scrotum. Testicular
descent requires foetal gonadotrophins which stimulate the
secretion of testicular Testosterone.
• In normal circumstance, the testes reach the inguinal
region by 12 weeks of gestation, pass through the inguinal
canal by 28 weeks and reach the scrotum by 33 weeks
CLINICAL IMPLICATIONS
ABNORMALITIES AFFECTING MALE:
• Hypospadias – When the fusion of the urethral folds is
incomplete leading to the occurrence of an abnormal
urethral opening on the inferior aspect of the penis
• Epispadias – A congenital absence of some part of the
upper wall of the urethra leading to the occurrence of an
abnormal urethral opening anywhere on the dorsal
surface of the penis. Occurs in both sexes and at various
degrees of severity, but males are more affected.
• Micropenis – Occurs due to insufficient androgen
stimulation to enable adequate growth of the male
external genitalia
Diagram showing hypospadias in the male
(Adapted from T. W. Sadler)
Abnormalities affecting males continues
• Klinefelter’s syndrome – Is a common major
abnormality of sexual differentiation in male. Such male
has a karyotype of 47,xxy. Individuals are usually
affected by infertility, gynaecomastia and impaired
sexual maturity
• Hermaphrodites – Abnormality of sexual
differentiation in which an individual has characteristics
of both sexes. True Hermaphrodites occur when the
individual has both testicular and ovarian tissue.
• Pseudohermaphrodites occurs when the genotypic sex
is masked by a phenotypic appearance that closely
resembles the opposite sex. In the male,
Pseudohermaphrodite is caused by reduced production
of androgenic hormones and MIS (AMH)
Abnormalities affecting the male continues
• Androgen insensitivity syndrome (Testicular feminization) –
individual has 46,xy chromosome compliment, but due to lack
of androgen receptors or failure of tissues to respond to
receptor-Dihydrotestosterone, the androgens produced by the
testes are unable to induce sexual differentiation of the male
genitalia. Hence, the person appears like a female, but without
fallopian tubes and uterus with a short vagina
• Cryptorchidism – this is a congenital abnormality in which
instead of the testes descending into the scrotum before birth
or few months after birth, it remains in the abdominal region
persistently. It occurs when the gubernaculum fails to develop
or pull the testes downward into the scrotum as a result of
disruption in the foetal hypothalamic – pituitary-testicular axis
• Congenital inguinal hernias/hydrocele
Diagram showing a patient with Androgen insensitivity
syndrome (Adapted from T. W. Sadler)


ABNORMALITIES AFFECTING THE FEMALE

• STRUCTURAL ANOMALIES: These anomalies results from
failure of the Paramesonephric (Müllerian) ducts to fuse or
remodel at the midline
• If the failure of the fusion of the Müllerian ducts occur along
the entire length of the midline - Double uterus (Uterus
didelphys) with two vaginas, two cervices and two separate
uterine horns
• If only the upper portion of the uterus fails to fuse, the
uterine body may remain separated as two horns –
Bicornuate uterus (Uterus bicornus)
• In milder situation, only a dimple may be noted in the middle
of the uterine fundus –arcuate uterus (Uterus arcuatus)
• When there is atresia of one of the paramesonephric duct,
the raminants of such duct lie as an appendage to the well
developed duct – Uterus bicornus unicolis
Some structural anomalies of the uterus
(Adapted from T. W. Sadler)
Structural anomalies in female continues
• Occasionally, only one side of the Müllerian system
develops leading to the formation of hemi-uterus and
one fallopian tube
• If after fusion, the midline fails to be resorbed, then a
septate uterus occur
• Vaginal atresia – occurs when the Sinovaginal bulb fails
to develop, while failure of the fusion of the sinovaginal
bulb will lead to formation of double vagina
• Imperforate hymen
only one of the Müllerian ducts develop
into hemi-uterus (Adapted from T. W. Sadler)
DEFECTS IN SEX DIFFERENTIATION IN
FEMALE
• Gonadal dysgenesis : Turner syndrome is the most
common of them.
• Individuals have a karyotype of 45,X with short stature,
webbed neck and infertility resulting from increased
loss of oocytes
• Hermaphrodites – True hermaphrodites (Ovotestes)
- Pseudohermaphrodites which in
female is caused by congenital adrenal hyperplasia with
increased androgen production. Individuals have ovaries
and a karyotype of 46, XX