The Genital Organs

Differentiation
By: E. Suryadi
Faculty of Medicine GMU
 Introduction
 At fertilization the genetic sex of an embryo is
determined, there is no morphological indication
of sex until the 7th week, when the gonads begin
acquire sexual characteristics.

 This period of early genital development is

referred to as indifferent stage organs.

 How the genital organs differentiation process?

And what are the influence factors?
 Differentiation of early embryonic
Blastomere
tissue s
Embryoblast

Trophoblast Allantois
Primordial
Endoderm Mesoderm
Ectoderm Germinal
Cells

Paraxialis Lateralis Migration

Intermediate

Crista urogenitalis Splachnicus Somaticus

Spermatogonium
Crista gonadalis
Mesothelium Sertoli Cell
Indifferent TDF Leydig Cell
Gonad mesenchym
 Embryonic structure ??
-Male genital organs

-Female genital organs

  Ovarium
 Tuba uteri
Embryonic structure  Uterus
(Indifferent gonad)  Vagina Female
 Clitoris genital
 Mesonephric tubulus  Labium minor
organ

 Mesonephric duct  Labium major

 Paramesonephric  Testis
duct  Epididymis
 Urogenital sinus  Ductus deferens
 Seminal gland
 Phallus Male
 Prostate gland genital
 Urogenital folds organ
 urethra
 Labioscrotal swelling
 penis
 scrotum
 Development of The Gonads

The gonad Cells are derived from three

sources of cells:
 1. mesothelium lining of the abdominal
wall and
 2. underlying mesenchyme
 3. primordial germ cells
 The Indifferent Gonads
 Gonadal development is the first indicated during
the fifth week when a thickened area of coelomic
epithelium.
 It develops on the medial aspect of urogenital
ridge and then becomes gonadal ridge
 Soon finger-like epithelium cords is formed, called
primary sex cords, grow into the underlying
mesenchyme.
 The indifferent gonad now consists of an outer as
a cortex and an inner as a medulla
 Origin of The Germ Cell
 Primordial germ cell (PGC) during third week
can be found on the posterior wall of the Yolk
sac near the origin of the allantois
 They are large size and clear cytoplasm
 PGC reach the gonads by migration
(amoeboid movement) around the wall of the
posterior gut and then through the dorsal
mesentery to the gonadal ridge.
 During migration is guided by laminin and
fibronectin (Extra- Cellular Matrix)
 A chemotactic influence from the gonads
guides the final stage of the migration
The Multiplication of The
Germ Cell by Mitosis
 The number of primary germ cell (PGC)
increases during their migration from a few
hundred to a few thousand
- after they have settled down in the gonad,
from a few thousand to about 7 million
 Mitotically active germ cell:
- in female are called oogonia
- in male are called spermatogonia
 The pattern of mitotic activity of oogonia and
spermatogonia is different
 Sex Determination
 Genetic sex is established at fertilization
 Gonadal sex is determined by the sex
chromosome ( X or Y )
 At the short arm Y chromosome has SRY gene
for TDF as a strong testis determining effect on
the medulla of indifferent gonad.
 TDF induces the gonadal cords to condense and
extend into medulla of indifferent gonad, where
sex cord branch and anastomose to form the
rete testis and gonadal cord become seminiferus
cord.
 The gonads then determine the type of sexual
differentiation that occurs in the genital ducts
and external genitalia.
 Development of testes
 In embryos with a Y chromosome the
primary sex cords condense and extend
into medulla of gonad.
 Here they branch and their ends
anastomose to form the rete testis.
 The prominent sex cords, called
seminiferus cord
 Soon lose their connections with the
germinal epithelium because of the
development of a thick fibrous capsule
called tunica albuginea
 The seminiferus cords develop into the
seminiferus tubules, the tubuli recti and the rete
testis. The seminiferus tubules are separated by
mesenchyme which give rise to the interstitial
cells (Leydig cell)
 The walls of the seminiferus tubules are
composed of two kinds of cells: sustentacular
cells of Sertoli derived from germinal epithelium
(mesothelium) and spermatogonia derived from
the primordial germ cells.
 Chromosome Y
 In Chromosome Y laid the SRY gene ( for a testis
determining factor (TDF)), which is located in the short
arm region of the Y chromosome.
 At sixth week SRY protein is produced so that :
 1. sertoli precursor (mesothelium cells) aggregate into
cords become tubulus seminiferus sertoli cell
produce Mullerian inhibitory factor (MIF) and
 2. mesenchymal cells of the gonadal ridge begin to
differentiate into Leydig cell  Leydig cells produce
testosteron
Mullerian inhibitory factor and testosteron influence the
development of the genital duct and the genital external
to differentiate in the male direction.
 Molecular regulation of genital
duct development
 SRY ---> master gene for testes development.
 SRY also upregulates SF1 ---> acts through another
transcription factor (SOX9) to induce defferentiation of
sertoli and leydig cells.
 Sertoli cells produce MIS/AMH that cause regression
which enters cells of target tissues where it may
remain or be converted to dihydrotestoterone by a 5α
reductase enzyme.
 Testosteron + dihydrotestoterone bind to a spesific
high-affinity intraceluller receptor protein, and
ultimately binds to DNA to regulate trancription of
tissue-spesific genes and their protein product.
 Tuberculum genitale Penis

Genital swelling Scrotum

Urethral endothelium Prostate

Y chromosome Dihydro-testosterone
Testis
Determining 5-alfa
Leydig cells Wolffian
factor reductase
Indifferent Duct
Testis Testosterone
gonad SOX9
Androgen
Sertoli cells
Binding Epididymis
Factor Vas deferens
Mullerian Seminal vesicle
Inhibiting Factor Germ cells Spermatozoa

Mullerian
Duct Degenerates

The developing process of the male genital organs

Development of Gonads
Development of The Genital Ducts
The Indifferent Stage consist two pairs of
genital ducts:
 1.ductus mesonephridicus (Wolffian ducts)

 2.ductus paramesonephridicus (Mullerian

ducts)
 Development of Genital Ducts
 Mesonephric duct  epididymis , defferen
duct & ejaculatory duct, seminal gland
 The Paramesonephric duct  develop
lateral to the gonads and mesonephric
ducts, pass caudally, parallel to the
mesonephric ducts, until they reach the
future pelvic region of the embryo, and to
develop to the tuba uterina, and uterus.
 Development of Genital Duct

 Testis fetal menghasilkan hormon untuk maskulinisasi yi

testosteron, dan substansi inhibiting mullerian (MIS). Sel
sertoli mulai menghasilkan MIS pd minggu ke-6 s/d -7.
Sel leydig mulai menghasilkan testosteron mulai minggu
ke-8.
Development of Male Genital Ducts
and Glands

1. Prostate
The glandular epithelium of
the prostate
differentiates from the
endodermal cells, and
the associated
mesenchyme
differentiates into the
dense stroma and
smooth muscle of the
prostate.
 Bulbourethral Glands

 Develop from paired outgrowths from the

spongy part of the urethra. The smooth muscle
fibers and the stroma differentiate from the
adjacent mesenchyme.
 Development of Male External Genitalia
 Induced by testosterone which produced by the
interstitial cells of the fetal testes.
 Con’t male external genital…

 The phallus develop  penis

 The urogenital folds forms the lateral wall of the urethral
groove  lined by a proliferation of endodermal cells,
the urethral plate,
 The urogenital folds fuse each other and forms spongy
urethra
 The surface ectoderm forms the penile raphe and
enclosing the spongy urethra within the penis
 During the 12th week a circular ingrowth of ectoderm
occurs at the periphery of the glans penis, and when its
breakdown it forms the prepuce (foreskin), which
covering fold of skin.
 Development of Inguinal Canals
 The inguinal canals form pathways for the testes to
descend from their intra-abdominal position through the
anterior abdominal wall into the scrotum
 Descent of the Testes
This is association with
- Enlargement of testes and
- atrophy of mesonepros,
- atrophy of paramesonepridicus duct,
- enlargement of processus vaginalis,
- enlargement of pelvis foetal,
- increase in abdominal pressure resulting
from the growth of abdominal viscera
 Cont….
By 26 weeks, the testes have descended
retroperitoneally (external to the peritoneum)
from the posterior abdominal wall to the deep
inguinal rings
.This change in position occurs as the fetal
pelvis enlarges and the trunk of the embryo
elongates.
Little is known about the cause of testicular
descent through the inguinal canals into the
scrotum, but the process is controlled by
androgens (e.g., testosterone) produced by the
fetal testes.
Male derivative Indifferent structure Female derivative
testis gonad ovary
Spermatozoa Primordial germ cells Ova
Seminiferus tubulus Sex cords Follicular cells
(sertoli cells)

Efferent ductules Mesonephric tubules Epoophoron

Epididymal duct, Mesonephric (Wolffian) Degenerates (ovarian,
ductus defferens duct round ligament )

Degenerates Paramesonephric Uterine tubes, uterus,

(Mullerian) duct part of vagina

Bladder, protaste Early urogenital sinus Bladder, paraurethral

urethra gland, urethra, vagina

Lower urethra, bulbo Definitive urogenital sinus Vestibule, Major

urethral gland vestibular gland
Penis Genital tubercle = phallus clitoris
Floor of penile urethra Urogenital fold Labia minora