Embryology pdf - د. ملاك

Genital System

Prof. Dr. Malak A. Al-yawer

Learning Objectives

 At the end of this lecture, the 1

medical student will be

able to:

 State the role of the Y chromosome in sex determination.
 Compare between male & female gonad development
 State the molecular regulation of genital duct development
 Compare between male & female duct development

(mesonephric/paramesonephric ducts) .

 Compare between male and female external genitalia

development

 List the differences between the descent of the gonads in

male and female

 State some clinical correlates

Sex differentiation

 is a complex process that

involves many genes, including

some that are autosomal.

 The key to sexual dimorphism

is the Y chromosome, which

contains the testis determining

gene called the SRY (sex-

determining region on Y) gene

on its short arm.

 SRY gene
 under its influence, 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 7

week of

development.

The genital or gonadal ridges

• Gonads appear initially as a pair

of longitudinal ridges, the genital
or gonadal ridges

• They are formed by proliferation

of the epithelium and a
condensation of underlying
mesenchyme.

• Germ cells do not appear in the

genital ridges until the 6

week

of development

Primordial germ cells

• Primordial germ cells originate in

the epiblast, migrate through the

primitive streak, and by the 3

week reside among endoderm cells

in the wall of the yolk sac close to

the allantois.

• During the 4th week, they migrate

by amoeboid movement along the

dorsal mesentery of the hindgut

,arriving at the primitive gonads at

the beginning of the 5

week and

invading the genital ridges in the 6

week.

• If they fail to reach the ridges, the

gonads do not develop. Hence, the

primordial germ cells have an

inductive influence on development

of the gonad into ovary or testis.

Indifferent gonad

• Shortly before and during arrival of primordial germ cells, the

epithelial cells of the genital ridge proliferates, and penetrate

the underlying mesenchyme and they form a number of

irregularly shaped cords called 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.

Testis

 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 4

month, the testis cords

 become horseshoe shaped, and their

extremities are continuous with those of the

rete testis

 are composed of primitive germ cells and

sustentacular cells of Sertoli derived from the

surface epithelium of the gland.

 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.

Interstitial cells of Leydig

• derived from the original mesenchyme of the

gonadal ridge which lie between the testis
cords.

• They begin development shortly after onset of

differentiation of these cords.

• By the 8

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.

Ovary

• In female embryos

, primitive sex cords

dissociate into irregular cell clusters.

• These clusters, containing groups of

primitive germ cells, occupy the

medullary part of the ovary. Later, they

disappear and are replaced by a vascular

stroma that forms the ovarian medulla.

• The surface epithelium of the female

gonad, unlike that of the male, continues

to proliferate. In the 7

week, it gives

rise to a second generation of cords,

cortical cords, which penetrate the

underlying mesenchyme but remain

close to the surface.

• At the 3rd month, Cortical cords split

into isolated cell clusters, with each

surrounding one or more primitive germ

cells.

• Germ cells subsequently develop into

oogonia, and the surrounding epithelial

cells, descendants of the surface

epithelium, form follicular cells

Influence of primordial germ cells on

indifferent gonad

Molecular Regulation of Genital Duct Development
In both males and females, SOX9 and WNT4 are
expressed in the gonadal ridges

Molecular Regulation of Genital Duct

Development in male

• SRY appears to act in conjunction with the autosomal gene

SOX9.

• Initially, SRY and/or SOX9

induce the testes to secrete FGF9

that causes tubules from the mesonephric duct to penetrate
the gonadal ridge.

• Next, SRY either directly or indirectly (through SOX9) up

regulates production of steroidogenesis factor 1 (SF1) that
stimulates differentiation of Sertoli and Leydig cells.

• SF1 working with SOX9 elevates the concentration of AMH

leading to regression of the paramesonephric (müllerian)
ducts.

Molecular Regulation of Genital Duct

Development in female

• WNT4 is the ovary-determining gene. This gene up regulates

DAX1, a member of the nuclear hormone receptor family, that
inhibits the function of SOX9.

• WNT4 regulates expression of other genes responsible for

ovarian differentiation

• Estrogens are also involved in sexual differentiation and under

their influence, the paramesonephric (müllerian) ducts are
stimulated to form the uterine tubes, uterus, cervix, and upper
vagina. In addition, estrogens act on the external genitalia at the
indifferent stage to form the labia majora, labia minora, clitoris,
and lower vagina

Indifferent Stage

• Initially, both male and female embryos have two pairs of genital

ducts:

1. mesonephric (wolffian) ducts and
2. paramesonephric (müllerian) ducts .
• The paramesonephric duct arises as a longitudinal invagination of

the epithelium on the anterolateral surface of the urogenital

ridge. Cranially, the duct opens into the abdominal cavity with a

funnel-like structure. Caudally, it first runs lateral to the

mesonephric duct, then crosses it ventrally to grow

caudomedially.

• In the midline, the

paramesonephric duct comes in

close contact with the

paramesonephric duct from the

opposite side.

• The two ducts are initially

separated by a septum but later

fuse to form the uterine canal.

• The caudal tip of the combined

ducts projects into the posterior

wall of the urogenital sinus, where

it causes a small swelling, the

paramesonephric or müllerian

tubercle .

• The mesonephric ducts open into

the urogenital sinus on either side

of the müllerian tubercle

Genital Ducts in the Male

• As the mesonephros regresses, a few

excretory tubules, the epigenital tubules,
establish contact with cords of the rete
testis and finally form the Efferent
ductules of the testis .

• Excretory tubules along the caudal pole

of the testis, the paragenital tubules, do
not join the cords of the rete testis .Their
vestiges are collectively known as the
paradidymis.

• Except for the most cranial portion, the

appendix epididymis, the mesonephric
ducts persist and form the main genital
ducts :

 the (ductus) epididymis.
 the ductus deferens.
 the ejaculatory duct.

Genital Ducts in the Female

• The paramesonephric ducts

develop into the main genital

ducts of the female.

• Initially, three parts can be

recognized in each duct( :

1. a cranial vertical portion that

opens into the abdominal cavity ,

(

2. a horizontal part that crosses the

mesonephric duct, and

3. a caudal vertical part that fuses

with its partner from the opposite

side.

• With descent of the ovary, the first

two parts develop into the uterine

tube and the caudal parts fuse to

form the uterine canal .

• When the second part of the paramesonephric ducts moves

mediocaudally, the urogenital ridges gradually come to lie in a

transverse plane.

• After the ducts fuse in the midline, a broad ligament of the uterus is

established which extends from the lateral sides of the fused

paramesonephric ducts toward the wall of the pelvis. The uterine tube

lies in its upper border, and the ovary lies on its posterior surface .

• The fused paramesonephric ducts give rise to the corpus and cervix of

the uterus. They are surrounded by a layer of mesenchyme that forms

the muscular coat of the uterus, the myometrium, and its peritoneal

covering, the perimetrium.

Vagina

• Shortly after the solid tip of the

paramesonephric ducts reaches

the urogenital sinus, two solid

evaginations (sinovaginal bulbs)

grow out from the pelvic part of

the sinus.

• The sinovaginal bulbs, proliferate

and form a solid vaginal plate.

• Proliferation continues at the

cranial end of the plate,

increasing the distance between

the uterus and the urogenital

sinus.

• (A:9weeks; B: end of 3

month)

• By the 5

month, the vaginal

outgrowth is entirely canalized.
The wing-like expansions of the
vagina around the end of the
uterus, the vaginal fornices, are
of paramesonephric origin .

• Thus, the vagina has a dual

origin, with the upper portion
derived from the uterine canal
and the lower portion derived
from the urogenital sinus.

• (C: Newborn)

The hymen

•

The lumen of the vagina remains separated from that of the
urogenital sinus by a thin tissue plate, the hymen, which
consists of

1. the epithelial lining of the sinus and
2. a thin layer of vaginal cells.
•

It usually develops a small opening during perinatal life.

Uterine and Vaginal Defects

• Duplications of the uterus result from lack of fusion of the

paramesonephric ducts in a local area or throughout their

normal line of fusion.

• If the sinovaginal bulbs fail to fuse a double vagina results
• If the sinovaginal bulbs do not develop at all, atresia of the

vagina, results

Vestigial Structures Derived

from Embryonic Genital Ducts

 Mesonephric Duct Remnants in Males

• The cranial end of the mesonephric duct

may persist as an appendix of the

epididymis

• Some mesonephric tubules may persist

as a small body, the paradidymis.

 Paramesonephric Duct Remnants in

Males

• The cranial end of the paramesonephric

duct may persist as a vesicular appendix

of the testis

• The prostatic utricle, a small saclike

structure that opens into the prostatic

urethra, is homologous to the vagina.

• The seminal colliculus, a small elevation

in the posterior wall of the prostatic

urethra, is the adult derivative of the

sinus tubercle. It is homologous to the

hymen in the female.

Mesonephric Duct Remnants in

Females

• The female may retain some

remnants of the cranial and
caudal excretory tubules in the
mesovarium, where they form
the epoophoron and
paroophoron, respectively.

• The cranial end of the

mesonephric duct may persist
as an appendix vesiculosa
found in the epoophoron

• a small caudal portion of

mesonephric duct may be
found in the wall of the uterus
or vagina. Later in life it may
form Gartner's cyst.

External Genitalia /Indifferent Stage

• In the 3

week of development,

mesenchyme cells originating in the

region of the primitive streak 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.

• Caudally the folds are subdivided

into

urethral folds

anteriorly and

anal folds

posteriorly.

• 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 6th week,

however, it is impossible to

distinguish between the two sexes.

External Genitalia in the Male (phallus)

• Development of the external genitalia in the

male is under the influence of androgens

secreted by the fetal testes and is

characterized by rapid elongation of the

genital tubercle, which is now called the

phallus.

• During this elongation, 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 3rd 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.

External Genitalia in the Male

(external urethral meatus)

• The most distal portion of the

urethra is formed during the 4

month

• 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.

External Genitalia in the Male

(Scrotal swellings)

• The genital swellings, known in

the male as the scrotal swellings,
arise in the inguinal region.

• They move caudally, and each

swelling then makes up half of
the scrotum.

• The two are separated by the

scrotal septum.

efects 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 . In rare cases, the

urethral meatus extends along the

scrotal raphe.

• Epispadias is a rare abnormality 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.

Defects in the Male Genitalia

• 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 ( double

penis) may occur if the

genital tubercle splits.

External Genitalia in the Female

• Estrogens stimulate development of

the external genitalia of the female.

• The genital tubercle elongates only

slightly and forms the clitoris

• Urethral folds do not fuse, as in the

male, but develop into the labia

minora

• Genital swellings enlarge and form

the labia majora .

• The urogenital groove is open and

forms the vestibule.

• Although the genital tubercle does

not elongate extensively in the

female, it is larger than in the male

during the early stages of

development.

• In fact, using tubercle length as a

criterion (as monitored by ultrasound)

has resulted in mistakes in

identification of the sexes during the

third and fourth months of gestation.

Descent of the gonads

• Both male and female gonads descend from the

10th thoracic level

• Females descend less than males

• In Males there are 3 phases of the descent

Caudal displacement due to regression of the

mesonephic kidneys

Transabdominal descent to the Inguinal ring

caused by regression of the Mullerian ducts

Transinguinal descent into the scrotum guided by

the gubernaculum into the vaginal process

Descent of the Testes

• Toward the end of the 2

month, the urogenital
mesentery attaches the
testis and mesonephros to
the posterior abdominal
wall.

• With degeneration of the

mesonephros, the
attachment serves

as a

mesentery for the gonad.

Descent of the Testes

• Caudally, it becomes

ligamentous and is known
as the caudal genital
ligament.

• Also extending from the

caudal pole of the testis is a
mesenchymal condensation
rich in extracellular
matrices, the
Gubernaculum .

The Gubernaculum

• Prior to descent of the testis, the Gubernaculum terminates

in the inguinal region between the differentiating internal

and external abdominal oblique muscles.

• Later, as the testis begins to descend toward the inguinal

ring, an extra-abdominal portion of the gubernaculum forms

and grows from the inguinal region toward the scrotal

swellings.

• When the testis passes through the inguinal canal, this extra-

abdominal portion contacts the scrotal floor (the

gubernaculum forms in females also, but in normal cases it

remains rudimentary).

• Normally, the testes
*

reach

the inguinal region

by approximately

weeks’

gestation,

migrate

through the

inguinal canal by

weeks, and

reach

the scrotum by

weeks.

• The process is influenced

by hormones, including
androgens.

• 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.

Processus vaginalis

• Independently from descent 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.

Hernias and Hydrocele

• 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 inguinal hernia (A) .

• 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 (B).

Cryptorchidism

• 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.

Descent of the Ovaries

•

Descent of the gonads is considerably less in the female than

in the male, and the ovaries finally settle just below the rim

of the true pelvis.

•

The cranial genital ligament forms the suspensory ligament

of the ovary

•

the caudal genital ligament forms

1. the ligament of the ovary proper and
2. the round ligament of the uterus which extends into the

labia majora

Summary

• The genital system consists of (a) gonads or primitive sex glands, (b) genital

ducts, and (c) external genitalia. All three components go through an indifferent
stage in which they may develop into either a male or a female.

• Y chromosome carries, on its short arm, SRY gene. Under its influence, male

development occurs and in its absence female character is established

• Sex of the embryo is determined at the time of fertilization
• The gonads do not acquire male or female morphological characteristics until

the 7th week of development.

• The primordial germ cells have an inductive influence on development of the

gonad into ovary or testis.

• Genes downstream from SRY include SOX9 and steroidogenesis factor (SF1)

that stimulate differentiation of Sertoli and Leydig cells in the testes.

• WNT4 is the master gene for ovarian development. It upregulates DAX1 that

inhibits the expression of SOX9. Then, WNT4 together with other downstream
genes causes formation of ovaries

Thank you

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