The Legendary Genius ..

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The Legendary Genius ..
Development of Gonads
- During 5th week: gonadal development occurs .
- Until 7th week: gonads are similar in both sexes .
Development of Gonads
Gonads are derived from 3 sources :
1
• Mesothelium (mesodermal
epithelium lining the coelomic cavity)
2
• Underlying mesenchyme
3
• Primordial germ cells
Indifferent Gonads
Indifferent Gonads

the initial period of genital development is
referred to as the indifferent stage of sexual
development.

The initial stages of gonadal development
occur during the fifth week ( 5 th )
A thickened area of mesothelium
develops on the medial side of the
mesonephros
Gonadal ridge: a bulge on the medial side of
mesonephros produced by:
•
Proliferation of mesothelium (cortex)
•
Proliferation (condensation ) of mesenchyme
(medulla)
Finger like epithelial cords or Gonadal cords
soon grow into the underlying mesenchyme
The indifferent gonad now consists of:
1- an external cortex
2 - an internal medulla
Indifferent Gonads

In embryos with an XX sex chromosome
complex, the cortex differentiates into an ovary
and the medulla regresses

In embryos with an XY sex chromosome
complex, the medulla differentiates into a testis
and the cortex regresses

Except for vestigial remnants .
Primordial Germ Cells
During folding of the embryo,
the dorsal part of the yolk sac
is incorporated into the embryo
These large, spherical cells are visible early in the
fourth week among the endodermal cells of the yolk
sac near the allantois
the primordial germ cells migrate
along the dorsal mesentery of the
hindgut to the gonadal ridges
Primordial Germ Cells

During the sixth week the primordial germ cells enter the
underlying mesenchyme and are incorporated in the
gonadal cords
oThe migration of the primordial germ cells is regulated
by the genes :
1- stella
2- fragilis
3- BMP-4.
o If they fail to reach the ridges, the gonad
remain indifferent or is absent…
Sex Determination
Sex Determination

Chromosomal and genetic sex is determined
at fertilization

It depends upon whether an X-bearing
sperm or a Y-bearing sperm fertilizes the Xbearing ovum

The type of gonads develop is determined by
the sex chromosome complex of the embryo
(XX or XY)
Sex Determination

Before the seventh week, the gonads of the two
sexes are identical in appearance called
indifferent gonads

Development of the male phenotype requires a
Y chromosome

The SRY gene for a testes-determining factor
(TDF) has been localized in the sex-determining
region of the Y chromosome ( on the short Arm
of this chromosome )

Two X chromosomes are required for the
development of the female phenotype
Sex Determination

The Y chromosome has a testes-determining effect on
the medulla of the indifferent gonad

The absence of a Y chromosome results in the
formation of an ovary

Testosterone, produced by the fetal testes, determines
the maleness

Primary female sexual differentiation in the fetus does
NOT depend on hormones

It occurs even if the ovaries are absent

Expression of the Sox9 and Fgf9 genes is involved in
the formation of the seminiferous cords.
Development of Testes
Development of Testes

Embryos with a Y chromosome usually develop
testes

The SRY gene for TDF on the short arm of the Y
chromosome acts as the switch that directs
development of indifferent gonad into testes
TDF induces the gonadal cords to
condense and extend into the medulla of
indifferent gonad, where they form rete
testes
The connection of gonadal cords or seminiferous
cords with the surface epithelium is lost as tunica
albuginea develops
Development of Testes

The development of a dense tunica
albuginea is the characteristic feature of
testicular development in a fetus
The seminiferous cords develop into
the seminiferous tubules, tubuli recti,
and rete testis
The enlarging testis separates
from the degenerating
mesonephros and becomes
suspended by its own mesentery
called mesorchium
The seminiferous tubules are separated by
mesenchyme that gives rise to the interstitial cell of
Leydig
Development of Testes

By the eighth week, these cells(Leydig) begin to
secrete testosterone and androstenedione

These hormones induce masculine
differentiation of the mesonephric ducts and
external genitalia

Testosterone production is stimulated by HCG
which reaches peak amounts during the 8- to
12-week period.

Fetal testes also produces a glycoprotein called
antimullerian hormone (AMH) or mullerian
inhibiting substance (MIS)
AMH is produced by sustentacular
cells of Sertoli
•AMH suppresses development of the
paramesonephric ducts
•Seminiferous tubules remain solid until
puberty
Development of Testes

The walls of seminiferous tubules are
composed of two kinds of cells :
2 . Spermatogonia, primordial sperm cells derived
from the primordial germ cells
1.
Sertoli cells, supporting cells derived
from the surface epithelium on the
testis
The rete testis becomes continuous with 15
to 20 mesonephric tubules that become
efferent ductules
- These ductules are connected with the
mesonephric duct
- It becomes the duct of the epididymis
In Summary …
Development of Genital Ducts
Development of Genital Ducts

Both male and female embryos have two pairs of genital
ducts

The mesonephric ducts (wolffian ducts) play an
important role in the development of the male
reproductive system

The paramesonephric ducts (mullerian ducts) have a
leading role in the development of the female
reproductive system

Till the end of sixth week, the genital system is in an
indifferent state, when both pairs of genital ducts are
present
A lateral outgrowth from the caudal end of
each mesonephric duct gives rise to the
seminal gland or vesicle
The secretion from this pair of glands
nourishes sperms
Distal to the epididymis, the mesonephric
duct acquires a thick investment of smooth
muscle and becomes the ductus deferens
The mesonephric duct between the duct
of this gland and the urethra becomes
the ejaculatory duct
Prostate

Multiple endodermal outgrowths arise from the
prostatic part of the urethra

Grow into surrounding mesenchyme

The glandular epithelium of the prostate
differentiates from these endodermal cells

The associated mesenchyme differentiates into
the dense stroma and smooth muscle of the
prostate
Bulbourethral Glands
pea-sized structures develop from
paired outgrowths from the spongy part
of the urethra .
 The smooth muscle fibers and the
stroma differentiate from the adjacent
mesenchyme.
 The secretions of these glands
contribute to the semen.

Development of External
Genitalia
Development of External Genitalia

Up to the seventh week of development the
external genitalia are similar in both sexes

Distinguishing sexual characteristics begin to
appear during the ninth week

External genitalia are not fully differentiated
until the twelfth week
Early in the fourth week,
Labioscrotal
swelling and
proliferating mesenchyme
urogenital
soon
develop
produces afolds
genital
tubercle
in
on
each
side
the
cloacal
both
sexes
atof
the
cranial
end
membrane
of the cloacal membrane
The genital tubercle soon elongates
to form a primordial phallus
Development of External Genitalia

1.
2.
When the urorectal septum fuses with the
cloacal membrane, it divides it into :
A dorsal anal membrane
A ventral urogenital (Urethral) membrane
The urogenital membrane lies in
the floor of a median cleft, the
urogenital groove, which is
bounded by urogenital folds
Development of Male
External Genitalia
Development of Male External
Genitalia

Masculization of the indifferent external
genitalia is induced by testosterone
The phallus enlarges and
elongates to become the
penis
The urogenital
folds form the lateral
walls of the urethral groove on the
ventral surface of the penis to form
the spongy urethra
The surface ectoderm fuses in the median
plane of the penis, forming a penile raphe
and enclosing the spongy urethra within
the penis
It grows towards the root of the penis to meet the
spongy urethra
At the tip of the glans of the penis, an ectodermal ingrowth
forms a cellular ectodermal cord
Development of Male External
Genitalia

This cord canalizes and joins the previously
formed spongy urethra

This completes the terminal part of the
urethra and moves the external urethral
orifice to the tip of the glans of the penis

During the twelfth week, a circular ingrowth
of ectoderm occurs at the periphery of the
glans penis
Development of Male External
Genitalia

When this ingrowth breaks down, it forms the
prepuce (foreskin)

It is adherent to the glans for some time

Usually not easy to retract at birth

Corpora cavernosa and corpus spongiosum
of the penis develop from mesenchyme in
the phallus
The labioscrotal swellings
grow towards each other
and fuse to form the
scrotum
The line of fusion of these folds
is clearly visible as the scrotal
raphe
Development of Male External
Genitalia

Agenesis of scrotum is an extremely rare
anomally
Development of Inguinal Canals

Inguinal canals develop in both the sexes
The gubernaculum passes
obliquely through the developing
anterior abdominal wall at the site
of future inguinal canal
The gubernaculum attaches
caudally to the internal surface of
the labioscrotal swellings
The processus vaginalis develops
ventral to the gubernaculum and
herniates through the abdominal wall
along the path formed by the
gubernaculum
Development of Inguinal Canals

The vaginal process carries extensions of
the layers of the abdominal wall before it,
which form the walls of the inguinal canal
The opening in the transversalis
fascia produced by the vaginal
process becomes the deep inguinal
ring
The opening created in the
external oblique aponeurosis
forms the superficial inguinal ring
In males, these layers also form the
coverings of the spermatic cord and testis
Descent of Testes
Testicular descent is associated with:
1
• Enlargement of the testes and atrophy of the
mesonephroi, allow caudal movement of the
testes
2
• Atrophy of paramesonephric ducts enables
testes to move transabdominally to the deep
inguinal rings
3
• Enlargement of processus vaginalis guides
the testes through the inguinal canal into the
scrotum
Descent of Testes

By 26 weeks the testes have descended
retroperitoneally 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 cause of testicular descent

The process is controlled by androgens
Descent of Testes

Passage of testis through the inguinal canal
may also be aided by the increase in intraabdominal pressure resulting from growth of
abdominal viscera

Descent of testes through the inguinal canals
into the scrotum usually begins during 26th week

It takes 2 to 3 days
Descent of Testes

More than 97% of full-term newborn males have
both testes in the scrotum

During the first 3 months after birth, most
undescended testes descend into the scrotum

Spontaneous testicular descent does not occur
after the age of one year

When the testis descends, it carries its ductus
deferens and vessels with it
DESCENT OF TESTIS
Fate of gubernaculum testis:
degenerates & disappears
 Fate of processus vaginalis:
During perinatal period:
1. The stalk normally obliterates
2. The caudal part forms the peritoneal
sac surrounding the testis (tunica
vaginalis)

ANOMALIES
Female ducts in male:
 Paramesonephric ducts develop in male
(it should disappear in males )
 Cause: failure of development of testes
& absence of müllerian inhibiting
substance
ANOMALIES
Hypospadius:

Most common anomaly of penis

Causes: inadequate production of androgens and/or
inadequate receptor sites for hormones

External urethral orifice opens on ventral surface of
glans or body of penis (80% of cases) Why ?
due to failure of canalization of ectodermal cord in glans
and/or failure of fusion of urogenital folds


In perineal hypospadius:
labioscrotal swellings fail to fuse & the orifice is located
between unfused halves of scrotum
ANOMALIES
Cryptorchidism (undescended testis):
 Occurs in up to 30% of premature males
and in approximately 3% to 4% of full-term males.

Cause: deficiency of androgens

May be unilateral or bilateral

In most cases, testes descend by the end of 1st year, if not , atrophy
occurs .

Men with a history of cryptorchidism have an increased risk of
developing testicular cancer. (risk of developing germ cell tumors,
especially in cases of abdominal cryptorchidism. )

Cryptorchid testes may be in the abdominal cavity or anywhere
along the usual path of descent of the testis, but they are usually in
the inguinal canal
CHRYPTORCHIDISM

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