2. Sex differentiation
• Sex differentiation is a complex process that involves
many genes.
• The key to sexual dimorphism is the Y chromosome,
which contains the testis-determining gene called the
SRY (sex-determining region on Y) gene.
• Under the influence of SRY protein (the testis-
determining factor), the male development occurs; in
its absence, female development is established.
• the sex of the embryo is determined genetically at the
time of fertilization,
• the gonads do not acquire male or female
morphological characteristics until the seventh week
of development.
3. The Genital Or Gonadal Ridges.
• During the 5th week a thickened area of
mesothelium develops on the medial side of the
mesonephros, genital ridges
• the genital or gonadal ridges are a pair of
longitudinal ridges formed by:
• 1. proliferation of the mesodermal epithelium
(mesothelium) and
• 2. a condensation of underlying mesenchyme
(embryonic connective tissue).
• Germ cells do not appear in the genital ridges
until the sixth week of development
4.
5. Primordial germ cells
• Primordial germ cells originate in the epiblast,
migrate through the primitive streak.
• by the 3rd week primordial germ cells reside
among endoderm cells in the wall of the yolk sac
close to the allantois .
• During the 4th week, they migrate by ameboid
movement along the dorsal mesentery of the
hindgut,
• at the beginning of the fifth week the primordial
germ cells arriving at the primitive gonads and
• in the sixth week they invading the genital ridges.
• The primordial germ cells have an inductive
influence on development of the gonad into ovary
or testis.
• If they fail to reach the ridges, the gonads do not
develop.
6. The primitive sex cords and indifferent gonad
• Shortly before and during arrival of primordial
germ cells, the epithelium of the genital ridge
proliferates, and epithelial cells penetrate the
underlying mesenchyme. Here they form a
number of irregularly shaped cords, the primitive
sex cords.
• In both male and female embryos, these cords are
connected to surface epithelium, and it is
impossible to differentiate between the male and
female gonad. Hence, the gonad is known as the
indifferent gonad.
7.
8. Congenital malformations:Determination of fetal sex
Ambiguous genitalia
• True hermaphroditism: having ovarian and testicular tissue either in the same or
opposite gonads (70 % are 46 XX, 20 % 46 XX/46 XY mosaicism, 10 % 46XY)
• Female pseudohermaphroditism: 46 XX, having ovaries, resulting from the
exposure from excessive androgens of female fetus. Virilization of external
genitalia (male external genitalia) occurs. Common cause is congenital adrenal
hyperplasia.
• Male pseudohermaphroditism: 46 XY having testis, with no sex chromatin.
external genitalia like female. It is caused by inadequate production of
testosterone and MIF (mullerian inhibiting factor) by testes.
• Androgen insensitivity syndrome (testicular feminization): Normal appearing
females with the presence of testes and 46 XY chromosomes. They are medically
and legally female. There is resistambce to the action fo testosterone at the
cellular receptor
• Mixed gonadal dysgenesis: very rare, having chromatin negative nuclei (sex
chromatin negative), a testis on one side, an undifferentiated gonad on the other
side. The internal genitalia are female, but may have male derivatives. The
external genitalia may vary from female to male.
9. Development of the Testis
• If the embryo is genetically male, the primordial germ cells
carry an XY sex chromosome complex.
• Under influence of the SRY gene on the Y chromosome, the
primitive sex cords continue to proliferate and penetrate
deep into the medulla to form the testis or medullary
cords.
• Toward the hilum of the gland, the cords break up into a
network of tiny cell strands that later give rise to tubules of
the rete testis.
• During further development, a dense layer of fibrous
connective tissue, the tunica albuginea, separates the
testis cords from the surface epithelium
• In the fourth month, the testis cords become horseshoe
shaped, and their extremities are continuous with those of
the rete testis
10.
11. Structures of the testis
• Testis cords are now composed of:
• 1. primitive germ cells and
• 2. sustentacular cells of Sertoli derived from the
surface epithelium of the gland and it produce
mullerian inhibiting hormone.
• 3. Interstitial cells of Leydig, derived from the
original mesenchyme of the gonadal ridge, lie
between the testis cords. They begin development
shortly after onset of differentiation of these cords.
• By the eighth week of gestation, Leydig cells begin
production of testosterone, and the testis is able to
influence sexual differentiation of the genital ducts
and external genitalia.
12.
13. Development of the Testis
• Testis cords remain solid until puberty, when they
acquire a lumen, thus forming the seminiferous
tubules.
• Once the seminiferous tubules are canalized, they
join the rete testis tubules, which in turn enter
the ductuli efferentes.
• These efferent ductules link the rete testis and
the mesonephric or wolffian duct, which
becomes the epididymis and ductus deferens
14. Descent of the Testes
• Extending from the caudal pole of the testis is a
mesenchymal condensation, the gubernaculum. This band of
mesenchyme terminates in the inguinal region, an extra-
abdominal portion of the gubernaculum forms and grows
from the inguinal region toward the scrotal swellings.
• Normally, the testes reach the inguinal region by
approximately 12 weeks' gestation, migrate through the
inguinal canal by 28 weeks, and reach the scrotum by 33
weeks. The process is influenced by hormones, including
androgens and MIS. The testis descends through the inguinal
ring and over the rim of the pubic bone and is present in the
scrotum at birth
• During descent, blood supply to the testis from the aorta is
retained, and testicular vessels extend from their original
lumbar position to the testis in the scrotum.
15. Covering of the testis
• The peritoneum of the abdominal cavity
forms an evagination on each side of the
midline into the ventral abdominal wall.
• This evagination, the processus vaginalis,
follows the course of the gubernaculum
testis into the scrotal swellings. Hence the
processus vaginalis, accompanied by the
muscular and fascial layers of the body
wall, evaginates into the scrotal swelling,
forming the inguinal canal
• The testis is then covered by a reflected
fold of the processus vaginalis.
• The narrow canal connecting the lumen of
the vaginal process with the peritoneal
cavity is obliterated at birth.
• In addition the testis becomes ensheathed
in layers derived from the anterior
abdominal wall through which it passes.
16.
17. Clinical Correlates:Hernias and Cryptorchidism
• The connection between the abdominal cavity and the
processus vaginalis in the scrotal sac normally closes in the first
year after birth. If this passageway remains open, intestinal
loops may descend into the scrotum, causing a congenital
indirect inguinal hernia. Sometimes, obliteration of this
passageway is irregular, leaving small cysts along its course.
Later, these cysts may secrete fluid, forming a hydrocele of the
testis and/or spermatic cord.
• In 97% of male newborns, testes are present in the scrotum
before birth. In most of the remainder, descent will be
completed during the first 3 months postnatally.
• However, in less than 1% of infants, one or both testes fail to
descend. The condition is called cryptorchidism and may be
caused by decreased androgen (testosterone) production.
• The undescended testes fail to produce mature spermatozoa,
and the condition is associated with a 3% to 5% incidence of
renal anomalies.
18. Genital Ducts: Indifferent Stage
• Initially, both male and
female embryos have
two pairs of genital
ducts:
• mesonephric (wolffian)
ducts and
• paramesonephric
(müllerian) ducts.
19. Mesonephric (wolffian) ducts
• The mesonephros consists of:
• 1. Mesonephric duct gives rise
to: Epididymis, vas deferens,
seminal vesicle and
ejaculatory duct
• 2. Mesonephric tubules;
• a. Epigenital tubules gives the
epididymis
• b. Paragenital tubules gives
the paradidymis
20. Genital Ducts in the Male
• As the mesonephros regresses,
1. the epigenital tubules,
establish contact with cords of
the rete testis and finally form
the efferent ductules of the
testis.
• 2. the paragenital tubules
along the caudal pole of the
testis, do not join the cords of
the rete testis. Their vestiges
are collectively known as the
paradidymis.
21. Development of the epididymis
• The mesonephric ducts persist and form the main genital ducts.
• Immediately below the entrance of the efferent ductules, the
mesonephric ducts elongate and become highly convoluted,
forming the (ductus) epididymis.
• Seminal vesicle arises as outbudding from the mesonephric
duct
• From the tail of the epididymis to the outbudding of the seminal
vesicle, the mesonephric ducts obtain a thick muscular coat and
form the ductus deferens.
• The region of the ducts beyond the seminal vesicles is the
ejaculatory duct.
• the most cranial portion of the mesonephric ducts forming the
appendix epididymis,
• The paramesonephric ducts in the male degenerate except for a
small portion at their cranial ends, the appendix testis
22.
23. External Genitalia: Indifferent Stage
• In the third week of development, mesenchyme cells around the cloacal
membrane form a pair of slightly elevated cloacal folds.
• Cranial to the cloacal membrane, the folds unite to form the genital
tubercle.
• Caudally, The cloacal folds are subdivided into urethral folds anteriorly
and anal folds posteriorly.
• In the meantime, another pair of elevations, the genital swellings,
becomes visible on each side of the urethral folds. These swellings later
form the scrotal swellings in the male and the labia majora in the female .
• At the end of the sixth week, however, it is impossible to distinguish
between the two sexes.
24. External Genitalia in the Male
• Development of the external genitalia in the male is under the influence of
androgens secreted by the fetal testes
• Rapid elongation of the genital tubercle, which is now called the phallus.
• The phallus pulls the urethral folds forward so that they form the lateral walls of
the urethral groove. This groove extends along the caudal aspect of the
elongated phallus but does not reach the most distal part (the glans).
• The epithelial lining of the groove, which originates in the endoderm, forms the
urethral plate.
• At the end of the third month, the two urethral folds close over the urethral
plate, forming the penile urethra. This canal does not extend to the tip of the
phallus.
• This most distal portion of the penile urethra is formed during the fourth month,
when ectodermal cells from the tip of the glans penetrate inward and form a
short epithelial cord. This cord later obtains a lumen, thus forming the external
urethral meatus.
• The genital swellings, known in the male as the scrotal swellings, arise in the
inguinal region. With further development, they move caudally, and each
swelling then makes up half of the scrotum. The two are separated by the
scrotal septum
25.
26. Development of male urethra
• the pelvic part of the urogenital sinus
in the male gives rise to the prostatic
and membranous parts of the urethra
• The epithelium of the urethra in both
sexes originates in the endoderm; the
surrounding connective and smooth
muscle tissue is derived from visceral
mesoderm.
• At the end of the third month,
epithelium of the prostatic urethra
begins to proliferate and forms a
number of outgrowths that penetrate
the surrounding mesenchyme. In the
male, these buds form the prostate
gland .
27. Clinical Correlates
Defects in the Male Genitalia
• In hypospadias, fusion of the urethral folds is
incomplete, and abnormal openings of the
urethra occur along the inferior aspect of the
penis, usually near the glans, along the shaft,
or near the base of the penis. The incidence of
hypospadias is 3-5/1,000 births
• Epispadias is a rare abnormality (1/30,000
births) in which the urethral meatus is found
on the dorsum of the penis . Although
epispadias may occur as an isolated defect, it is
most often associated with exstrophy of the
bladder and abnormal closure of the ventral
body wall.
• Micropenis occurs when there is insufficient
androgen stimulation for growth of the
external genitalia. Micropenis is usually caused
by primary hypogonadism or hypothalamic or
pituitary dysfunction.
• Bifid penis or double penis may occur if the
genital tubercle splits