Development of The Limbs: Mesoderm and Migrating Myotomes

Prof.
Hany Shawky Nadim 1 Systemic Embryology
DEVELOPMENT OF THE LIMBS

nd
Before the 2 month, the embryo has no limbs. They
develop totally during the 2nd month (i.e., 5-8 wks).
5th week
- Four limb buds develop from the body. The
upper limb buds appears 2 days before the
lower limb bud (days 28 & 30 successively).
- Each limb bud is formed of:
1. Outer ectodermal covering forms the skin. At the tip of
each bud, there is an ectodermal thickening called apical
ectodermal ridge (AER) which has inductive influence on
the differentiation of limb mesoderm.
2. Inner mesodermal core derived from the lateral plate
mesoderm and migrating myotomes.
6th week
- A hand plate appears in the upper limb bud & a foot plate in
the lower limb bud.
- Digital rays appear due to mesodermal condensations in the
hand & footplates.
- Bones appear inside the bud, at first as mesodermal condensations which
undergo chondrification followed by ossification. They appear in a proximo-
distal order.
7th week
- Webs between the rays break down and the digits become
separated by notches.
- Each limb bud becomes divided into 3 segments; arm, forearm
& hand plate in the UL and thigh, leg & foot plate in the LL.
- A muscle mass develop inside the bud around the bones.
8th week
- The digits become free
- The limb buds undergo adduction and rotation:
Upper limb buds Lower limb buds
Rotates 90° laterally. 90° medially.
Results:  Digits: -The preaxial digit - The preaxial digit (big
(thumb) becomes lateral. toe) becomes medial.
 Muscles: -The flexors become ant. -The flexors become post.
& the extensors post. & the extensors ant.
 Bones: -The preaxial border -The preaxial border
(radial) becomes lateral. (tibial) becomes medial
3rd month: Nails appear
4th month: fingerprints develop & the muscles become strong & the baby starts to kick against the
uterine wall. The mother starts to feel the movements called quickening
 lnnervation of the limb buds:

- Nerves grow from the neural tube, their ventral rami enter each bud to
supply its skin and muscles:
1. The UL. bud is supplied by ventral rami of C4 to T2 [brachial plexus].
Prof. Hany Shawky Nadim 2 Systemic Embryology
2. The LL. Bud is supplied by ventral rami of L1 to S4 [lumbar & sacral plexuses].
- Each spinal nerve supplies a skin area called dermatome. As the buds grow, the spinal
nerves are elongated. As a result, the cranial dermatomes (e.g. C.4,5,6 in the case of the UL)
occupy the preaxial border whereas the caudal dermatomes (C.8 & T.1,2) occupy the
postaxial border. The central dermatome (C.7) becomes buried in the proximal part of the limb but
reappears distally in the hand.
ANOMALIES:
1. Amelia: Absence of one or more limbs.
2. Meromelia: The limb is represented only by the hand or foot.
3. Syndactyly: Fused one or more digits.
4. Polydactyly: Supernumerary digits.
5. Bradydactyly: Short digits.
6. Club foot: The feet are plantar-flexed & inverted constantly.
7. Cleft hand or foot [Lobster Claw Deformity]: One or more
middle digit(s) is absent. Thus, the hand (or foot) is divided into two parts.
In each part, the digits are fused.
DEVELOPMENT OF CARDIOVASCULAR SYSTEM
 It is the first system to function. The heart starts to beat in the middle of the 3rd. week.
 The C.V.S. is totally mesodermal in origin.
DEVELOPMENT OF THE HEART
FORMATION OF THE HEART TUBE (CARDIAC LOOP):

- It develops from 3 mesodermal sources in the cranial end of the embryonic disc:
1. Pericardial Sac: is the transverse cranial part of the U-shaped intra-
embryonic coelom; situated caudal to the septum transversum.
2. Cardiogenic plate: is an area of splanchnic mesoderm, situated ventral to
the pericardial sac. In it, right and left endocardial heart tubes develop and
fuse together in the middle.
3. Myoepicardial Mantle: is a layer of splanchnic mesoderm situated between
the pericardial sac and the endocardial heart tube. It spreads to form a coat
around the heart tube.
The endocardium is derived from the endocardial heart tube.
The myocardium is derived from the myoepicardial mantle.
The epicardium is derived from the visceral layer of pericardial sac.
- As a result of folding, the heart tube and the pericardial sac rotate with the head fold. Finally, the
heart tube becomes dorsal to the pericardial sac.
- The endocardial heart tube invades the pericardial sac from its dorsal aspect
dividing it into a visceral layer and a parietal layer.
- Five chambers appear as dilatations (separated by constrictions) in the heart tube.
In a caudo-cranial order, they are: sinus venosus, atrium, ventricle, bulbus cordis,
truncus arteriosus.
- The 2 ends of the heart tube are connected to the intra-embryonic vessels:
1. At the venous end, each horn of sinus venosus receives 3 veins:
a- Vitelline vein from the yolk sac.
b- Umbilical vein from the placenta.
c- Common cardinal vein from the body wall.
2. At the arterial end, the truncus arteriosus divides into 2 horns, each is
connected to arteries.
- The heart tube elongates forming an S-shaped cardiac loop. The bulbus cordis
shifts to the right side of the ventricle. The atrium expands transversely, bulging on
either side of the bulbus cordis forming auricles.
FATE OF THE SINUS VENOSUS

- Initially, the sinus venosus opens into the middle of the back of the primitive
atrium. It divides into two horns (right & left). Each horn receives 3 veins: umbilical v., vitelline
v. & common cardinal v.
- The opening between the sinus venosus and the atrium (sino-atrial orifice) has the shape of a
vertical slit. Its edges are called the right and left venous valves.
- Fate: Left-to-right shunt of venous blood occurs; as a result:
1. The sino-atrial orifice moves to the right and opens in the part of the primitive atrium that
will become the right atrium.
2. The right horn progressively enlarges and becomes incorporated into the right atrium due
to widening of the sino-atrial orifice giving the smooth posterior part of the right atrium
called sinus venarum.
3. The left horn (and body) diminishes forming the coronary sinus.
4. From the 6 veins, 3 veins disappear and 3 persist forming veins that open into the right
atrium:
 The right vitelline v. forms the upper part of IVC
 The right common cardinal v. forms the lower part of SVC
 The left common cardinal v. forms the oblique vein of left atrium.
5. The venous valves:
a. The right venous valve forms the crista terminalis which contains the SA node.
b. The left venous valve is incorporated with the inter-atrial septum.
SEPTATION OF ATRIA
 In the A-V canal between the atrium and ventricle, two endocardial cushions, ventral and dorsal
project from the walls and fuse together forming the septum intermedium which divides the A-V
canal into right and left halves. The upper part of each half (towards the atria) is added to the
corresponding atrium while the lower parts form the mitral and tricuspid
orifices. Local endothelial proliferations form the cusps of the A-V valves (3
cusps in the tricuspid valve & 2 cusps in the mitral valve).
 The primitive atrium is divided into right and left chambers by the
development of an inter-atrial septum. In spite of that, throughout the
intrauterine life, this septum always keeps a gap connecting both atria. Steps of
septum formation:
1. The Septum Primum:
- A thin crescentic membrane grows from the roof of the atrium and
descends towards the septum intermedium, but is separated from it by the
foramen primum (ostium primum) which allows free communication
between the right and left sides.
- The foramen primum becomes progressively smaller and is finally closed.
Just before complete closure of the foramen primum, the upper part of the
septum primum ruptures forming another opening, the foramen secundum
which widens cranially.
2. The Septum Secundum:
- Another crescentic membrane grows from the roof of the atrium,
immediately to the right side of the septum primum. The opening below the
septum secundum is called the foramen ovale.
- Blood in the right atrium passes to the left atrium via a tortuous S-shaped
course through the foramen ovale and foramen secundum. Passage of blood
in an opposite direction is prevented by the flap-like valvular action of the
remaining lower part of the septum primum, closing the foramen ovale.
 After birth, the pressure in both atria becomes equal and the 2 septa fuse. The
septum primum in the site of the foramen ovale forms the fossa ovalis. The
margins of the septum secundum around the fossa form the limbus fossa ovalis
(annulus ovalis).
 The left atrium receives a common pulmonary vein which is formed by union
of four pulmonary veins from the lungs. The proximal part of this pulmonary
venous system is absorbed into the wall of the developing left atrium. As a
result, the four pulmonary veins open directly into the left atrium.
In Summary; each atrium is derived from 3 sources:

right atrium left atrium
1. right half of the primitive atrium 1. left half of the primitive atrium
2. absorbed right horn of sinus venosus 2. absorbed pulmonary veins
3. upper part of the right A-V canal 3. upper part of the left A-V canal
THE REMAINING CHAMBERS

 The lower part of the bulbus cordis, together with the common ventricle form
one chamber which has trabeculated wall. It forms the rough inflowing parts
of both ventricles.
 The remaining smooth part of the bulbus cordis forms the smooth outflowing
parts of both ventricles.
 The truncus arteriosus is divided into ascending aorta and pulmonary trunk.
Five septa divide these chambers

 Two septa in the bulbo-ventricular chamber:
1. Muscular interventricular septum: grows as a crescentic partition from
the floor of the chamber between both ventricles.
2. Membranous interventricular septum: fills the gap between the upper
crescentic border of the muscular septum and the septum intermedium,
which is called the interventricular foramen. It is derived from the
septum intermedium and the proximal bulbar septum.
 Two septa in the conus cordis:
1. Proximal bulbar septum: comes from right and left bulbar ridges
which fuse together separating the infundibulum of right ventricle
(ventrally) and the vestibule of left ventricle (dorsally). It extends and
shares in the formation of the membranous interventricular septum
2. Distal bulbar septum: comes from right and left bulbar ridges which
fuse together separating the pulmonary orifice (ventrally) and the
aortic orifice (dorsally). Each orifice develops three valve swellings
which become hollowed superiorly forming the semilunar cusps. The
cusps become repositioned to become 1 ant. + 2 post in the aortic
orifice and 1 ant. + 2 post. in the pulmonary orifice.
 One septum in the truncus arteriosus:
Spiral aortico-pulmonary septum: comes from 2 spiral ridges which fuse
together separating the pulmonary trunk and the ascending aorta which are
enclosed by a single coat of serous pericardium.
In Summary; each ventricle is derived from 2 sources:
right ventricle left ventricle
1 1
inflowing Right /2 of the bulbo- Left /2 of the bulbo-
part ventricular chamber ventricular chamber
outflowing Ventral 1/2 of the proximal Dorsal 1/2 of the proximal
part part of bulbus cordis part of bulbus cordis
The myocardium of each ventricle shows spongework cavitation resulting
in the formation of the trabeculae carnae, papillary muscles and
chordae tendinae.
ANOMALIES OF THE HEART

Frequency: Congenital Heart Defects (C.H.D.) occurs in 6-8 per 1000 births.
Causes:
a. Genetic causes: e.g., Turner & Down Syndromes.
b. Environmental causes: e.g., German measles virus.
Types:
(1) Abnormal Position:
a. Dextrocardia = right-sided heart; alone or as a part of situs inversus
totalis.
b. Ectopia cordis = a heart protruding through a median gap in the chest
wall; due to faulty development of the sternum (bifid sternum).
(2) Septal Problems:

1. Atrial Septal Defects (ASDs): due to:
a. Underdeveloped septum secundum.
b. Excessive resorption of septum primum
c. Failure of fusion between the 2 septa which are normal.
This is called Probe-patent foramen ovale & occurs
in 25% of NORMAL hearts.
2. Ventricular Septal Defects (VSDs):

a. Membranous VSD (Roger’s disease) due to failure of
formation of the membranous part of the
interventricular septum.
b. Muscular VSD one or multiple holes (Swiss cheese
VSD) in the muscular I-V septum due to excessive
cavitation during trabeculation of the medial walls of
both ventricles.
3. Abnormal division of the truncus arteriosus:

a. Persistent truncus arteriosus: the aortico-pulmonary septum fails
to develop; thus one big vessel receives blood from both ventricles
& distributes it to the pulmonary & systemic circulation.
b. Transposition of the great vessels: the aortico-pulmonary septum
is formed but is non-spiral; thus the aorta arises from the Rt.
ventricle and the pulmonary trunk from the left ventricle.
c. Congenital stenosis or atresia of the pulmonary or aortic
orifice: the aortico-pulmonary septum divides the truncus
arteriosus unequally.
d. Fallot’s Tetralogy: same as the previous anomaly but with
additional features
1.Pulmonary stenosis.
2.Hypertrophy of the right ventricle.
3.Membranous VSD.
4.Overriding of aorta on the ventricular septum (i.e., receiving blood from
both ventricles).
N.B:The commonest congenital heart defect is membranous VSD, called Roger’s disease.
ASD is also common especially in females (VSD is more common in males).
Fallot’s Tetralogy is the commonest cause of neonatal cyanosis (blue baby).
DEVELOPMENT OF ARTERIES
 At first, there are 6 aortic arches on each side of the neck (each runs in the
corresponding pharyngeal arch). They connect one horn of the ventral aortic sac
(which arises from the truncus arteriosus) to the corresponding dorsal aorta
 Fate: arches 1, 2 & 5 disappear, the rest give the following
arch Right Left
3rd The common carotid a. & internal carotid a. (the external carotid arises
as an outgrowth).
4th Part of the right subclavian a. Part of the arch of aorta
6 th
Proximal part  right pulmonary a. Proximal part left pulmonary a.
Distal part disappears. Distal part ductus arteriosus.
1. The arthe arch of aorta is derived from 3 sources:

a. Left horn of aortic sac.
b. 4th. left aortic arch.
c. Part of the left dorsal aorta till the 7th intersegmental artery.
2. The innominate artery is derived from the right horn of the aortic sac.
3. The subclavian arteries:
a. The right: is derived from the right 4th aortic arch + part of the right dorsal
aorta + the right 7th intersegmental artery.
b. The left: is derived from the left 7th intersegmental artery.
4. The descending aorta is derived from the part of the left dorsal aorta caudal to
the left 7th intersegmental branch + the single distal aorta.
N.B: The recurrent laryngeal nerve is the nerve of the 6th pharyngeal arch. It is pulled
down by the 6th aortic arch forming a loop before it returns to the neck.
 On the left side, it hooks around the ductus arteriosus in the thorax.
 On the right side, the distal part of the right 6th aortic arch + the right 5th aortic
arch disappear; the nerve hooks around the right subclavian artery in the neck (i.e.,
the derivative of the right 4th arch).
B- Fate of the Branches of the Dorsal Aortae:
I. The intersegmental (somatic) branches: pass laterally between somites:
- Cervical: 1st – 6th: are connected by longitudinal anastomotic channels which form
the vertebral artery and other arteries. The 7th  subclavian a.
- Thoracic: 1st - 11th  intercostal arteries & 12th  subcostal a.
- Lumbar: 1st - 4th  lumbar arteries & 5th  common iliac a.
- Sacral:  the lateral sacral arteries.
II. Lateral splanchnic arteries:
 Supply the structures derived from the intermediate cell mass mesoderm.
 Derivatives:
1. Phrenic arteries.
2. Middle suprarenal arteries.
3. Renal arteries.
4. Gonadal arteries.
III. Ventral splanchnic arteries:

A- Vitelline arteries supply the gut.
1. Celiac artery  foregut.
2. Sup. mesenteric artery  midgut.
3. Inf. mesenteric artery hindgut.
B- Umbilical arteries (right & left): become connected
to the common iliac arteries. Each forms the internal
iliac a. & continues as the umbilical artery. The distal part
of the common iliac forms the external iliac a.
N.B: Caudal to the origin of the common iliac a., the dorsal aorta is
reduced in size  the median sacral a.
Anomalies of Arteries:
 Coarctation of aorta: is narrowing of a segment of
the aorta. Its cause is unknown (may be fetal
hypoxia  hypertrophy of the wall)
 Patent Ductus Arteriosus (PDA): alone or 2ry. to
preductal coarctation of aorta
DEVELOPMENT OF VEINS
The embryo has 3 pairs of major veins:
I. Vitelline Veins: are 2 veins which drain the yolk sac and pass through the septum transversum
(ST) to open in the sinus venosus (SV). Fate:
(1) Caudal to the ST: they form the portal v., its right and left
branches & its 2 tributaries (sup. mesenteric & splenic).
(2) Inside the ST: they form the hepatic sinusoids.
(3) Between the ST & SV: they form 2 hepatic veins which
unite into a common hepatic v. that opens into the right
atrium & gives the upper segment of IVC
II. Umbilical Veins: are 2 veins which carry oxygenated blood
from the placenta to the SV after passing through the ST.
Fate: The right vein disappears & the left vein also
disappears except the part caudal to the ST which remains
(from the umbilicus to the left branch of portal v.). The part inside the ST is replaced by the
ductus venosus that ends in the common hepatic v.
III. Cardinal Veins: 2 veins, which drain the body wall & formed by
union of anterior and posterior cardinal veins. Fate:
A. Common cardinal veins:
(1) Right lower part of SVC (below the azygos v.).
(2) Left oblique vein of left atrium.
B. Anterior cardinal veins: become connected by an oblique
anastomosis which forms the left innominate v. while the right vein
forms the right innominate v. + the upper part of SVC.
C. Posterior cardinal veins: become connected by an iliac anastomosis
which  left common iliac v. The right vein  root of azygos v. +
right common iliac a.
Anomalies of Veins: SVC: double SVC or left SVC - IVC: double IVC or absent IVC
FETAL CIRCULATION
The lungs do not function during intrauterine life. Three types of blood are found:
I. Highly Oxygenated Blood:
1. Passes from the placenta along the left umbilical vein to the left branch of portal vein.
2. Then reaches the IVC by one of 2 ways:
a. Mostly via the ductus venosus (i.e., by-passing the liver).
b. To a little extent via the liver sinusoids to the hepatic veins.
A physiological sphincter in the ductus venosus diverts blood
to the liver sinusoids when blood flow in the umbilical v. is
high (e.g., during uterine contraction) to prevent overloading
of the heart.
3. In the IVC, oxygenated blood mixes with little deoxygenated
blood returning from lower extremities & abdomen; this
highly oxygenated blood reaches the right atrium, where:
a. Most of it passes to the left atrium via the foramen ovale as
pressure in the left atrium is lower than the right.
b. Little amount passes to the right ventricle, then to the non-
functioning lungs & returns to the left atrium via the
pulmonary veins.
4. Blood in the left atrium mixes with little blood returning from
the lungs and passes to the left ventricle. This highly
oxygenated blood is distributed to the heart (via the coronary
arteries) + head, neck and upper limbs (via the 3 big branches
of the arch of aorta).
II. Deoxygenated Blood:
 Returns to the right atrium via the SVC (from the head, neck and upper limb) and via the coronary sinus
(from the heart).
 This blood passes to the right ventricle; to the pulmonary trunk, mainly to its left branch  to
the ductus arteriosus to the arch of aorta after the origin of its 3 big branches.
III. Mixed Blood:
The mixed blood (oxygenated from the ascending aorta + unoxygenated from the ductus
arteriosus) passes in the descending aorta where it:
a. Supplies the abdomen and lower limbs.
b. Passes in the common iliac arteries to the internal iliac arteries to the umbilical
arteriesto the placenta where gaseous exchange occurs and the cycle is repeated.
Changes just after birth:
1. Pressure is equalized in both atria because:
a. Respiration begins due to exposure to cold temperature so,
blood returns from the functioning lungs to the left atrium.
b. The umbilical cord is ligated, so, no blood returns via the
occluded umbilical vein to the right atrium.
2. As a result, the septum primum and secundum fuse together 
closure of the foramen ovale.
3. The occluded umbilical v.  the ligamentum teres of the liver.
4. The occluded distal parts of the umbilical arteries  the medial
umbilical ligaments.
5. The occluded ductus venosus the ligamentum venosum.
6. The occluded ductus arteriosus  the ligamentum arteriosum.
DEVELOPMENT OF THE RESPIRATORY SYSTEM

 A median longitudinal groove called the laryngo-
tracheal groove appears in the floor (i.e., ventral
wall) of the primitive pharynx.
 The 2 margins of the laryngo-tracheal groove fuse
together in a caudo-cranial direction forming a
septum separating the lumen of the primitive
pharynx into 2 parts:
a. Dorsal part = the pharynx & esophagus.
b. Ventral part called laryngo-tracheal tube.
 The laryngo-tracheal tube forms the lining
epithelium of the larynx, trachea, bronchial tree and alveoli. The
surrounding splanchnic mesoderm forms the cartilages, smooth
muscles, connective tissue and blood vessels of the respiratory
system.
 Fusion of the laryngo-tracheal folds stops cranially leaving a
communication between the laryngo-tracheal tube and the
pharynx. This opening is called the laryngeal inlet. The inlet is obliterated
transiently between the 8th and 10th weeks. During recanalization of the larynx,
folds appear forming the vocal cords (true & false).
 The caudal end of the laryngo-tracheal tube grows down on the ventral aspect of
the foregut, where it divides into right and left lung buds.
 The lung buds undergo the following:
A- Division:
- Each lung bud forms a main bronchus. The right bud is wider and more
vertical than the left. Each main bronchus divides into secondary (lobar)
bronchi (3 on the right side & 2 on the left side).
- The 2ry bronchi divide giving tertiary (segmental) bronchi; each becomes
surrounded by a mass of splanchnic mesoderm giving a broncho-pulmonary segment.
- Repeated division continues. By the 6th month, terminal bronchioles are formed.
- Further division continues for sometime after birth (up to 8 years) till the respiratory
bronchioles and alveoli are formed (a total of 24 orders of division).
B- The surrounding splanchnic mesoderm forms cartilaginous plates, smooth muscles,
connective tissue & blood capillaries.
C- Invasion of the pleura: each lung grows laterally around the foregut and
invaginates the part of the intraembryonic coelom, (i.e., the pericardio-
peritoneal canal) which gives the pleural sac. The visceral pleura is
derived from the splanchnic mesoderm, whereas the parietal pleura is
derived from the somatic mesoderm. Therefore, the visceral pleura is
supplied by autonomic nerves and is insensitive whereas the parietal pleura
is supplied by somatic nerves and is sensitive to pain.
Lung Maturation: it passes into 4 stages:

1. Pseudoglandular period (up till the 4th. month): only terminal bronchioles
are formed. Histologically, the lung resembles an exocrine gland. Elements
involved in gaseous exchange are not formed yet; therefore a fetus born at this stage cannot
survive.
2. Canalicular period (4-6 months): Respiratory bronchioles & alveolar
ducts develop. Vascularization of the lung occurs. Survival is
theoretically possible but in reality, a fetus born at this stage dies even
with intensive care.
3. Terminal sac period (6th month - birth): alveolar sacs are formed. They
are lined by cuboidal epithelium (Type I pneumocytes). Capillaries bulge
into them. Type II pneumocytes appear & secrete surfactant which is a
phospholipid that lines the alveoli & help in their expansion after birth.
Surfactant production reaches adequate levels by the 7th month. A fetus
born by that time can survive with intensive care.
4. Alveolar period (from late prenatal period - 8 years postnatal): The
number of alveoli increases (95% of the alveoli develop after birth). Mature
(thin walled) alveoli don’t develop except after birth. Now, the alveolo-
capillary membrane is thin enough to permit sufficient gaseous exchange.
Breath Movements:
 Before birth, they can be detected by ultrasonography. As the lung is not a
respiratory organ before birth, these prenatal breath movements cause:
1. Suction of amniotic fluid into the airway.
2. Training of the respiratory muscles.
 At birth, the fluid in the airways (amniotic fluid + bronchial secretions) becomes replaced by air
via 2 mechanisms:
1. Some become expelled by pressure on the thorax during labour.
2. The majority is absorbed by pulmonary capillaries & more importantly by pulmonary
lymphatics.
 Medicolegally, the lungs of a baby who was born alive & died after birth contain air, thus can
float on water. On the other hand, the lungs of a still born baby sink.
Anomalies:
(1) Esophageal atresia & tracheo-esophageal fistula.
Esophageal atresia = obliteration of the esophagus & fistula = abnormal
communication between it and the trachea. This causes impossible feeding &
aspiration of milk into the lungs. Before birth, it causes polyhydramnios.
(2) Surfactant deficiency = hyaline membrane disease (HMD) which is the major
cause of respiratory distress syndrome (RDS).
DEVELOPMENT OF THE GIT
 During folding, the endoderm is enclosed inside the embryo forming the lining of the
gut tube which is formed of 3 parts:
1. Fore-gut in the head fold. Closed cranially by the bucco-pharyngeal membrane.
2. Hind-gut in the tail fold. Closed caudally by the cloacal membrane.
3. Mid-gut in between. Connected to the yolk sac by the vitello-intestinal duct.
 The cranial end of the fore-gut is called the primitive pharynx. The respiratory
system is derived from it.
 The gut is suspended from the posterior abdominal wall by a double-layered dorsal
mesentery. Its parts are named according to the organ connected to it (i.e. dorsal
mesogastrium, mesoduodenum, mesentery & mesocolon).

 Three arteries derived from the dorsal aorta, pass between the two layers of the
dorsal mesentery to supply the gut. These are:
1. Coeliac artery  supplies the fore-gut.
2. Superior mesenteric artery  supplies the mid-gut.
3. Inferior mesenteric artery  supplies the hind-gut.
 A ventral mesentery, called ventral mesogastrium (derived from the septum
transversum) connects the stomach and the cranial part of the duodenum to the
anterior abdominal wall.
FATE OF THE GUT TUBE:

I. Derivatives of the fore-gut:
1. The part of the G.I.T above the opening of the common bile duct into
the duodenum + the liver & pancreas.
2. The respiratory passages + the derivatives of the pharyngeal pouches.
II. Derivatives of the mid-gut:
The part of the G.I.T from the opening of the common bile duct till the
junction between the right 2/3 and left 1/3 of the transverse colon.
III. Derivatives of the hind gut:
1. The part of the G.I.T from the junction between the right 2/3 and left
1/3 of the transverse colon till the junction between the upper and
lower parts of the anal canal.
2. Parts of the uro-genital system.
 The mucosa is derived from the endoderm of the gut tube.

 The submucosa, musculosa & serosa are derived from the surrounding splanchnic mesodem.
THE FOREGUT
STOMACH
Appears as a fusiform dilatation in the fore-gut but lies at a relatively high level & has:
 Two ends (cardiac & pyloric) which lie in the midline.
 Two borders (ventral & dorsal) which are equal in length.
 Two surfaces (right & left) which are related to the right & left vagi respectively.
 Two peritoneal folds, a ventral mesogastrium connecting the ventral border to the
anterior abdominal wall & a dorsal mesogastrium connecting the dorsal border to
the posterior abdominal wall.
LATER:
 The dorsal border grows faster than the ventral border forming the greater curvature.
 The stomach rotates 90° to the right around its longitudinal axis. Thus;
- The right surface becomes posterior & the left becomes anterior.
- The right vagus becomes the posterior gastric nerve & the left vagus becomes the
anterior gastric nerve.
- The lesser curvature faces right & the greater curvature faces left.
- The dorsal mesogastrium becomes stretched & elongated towards the left, thus a
peritoneal recess, the lesser sac, is formed behind the stomach.
 The stomach descends to a lower level due to elongation of the esophagus.
 The liver develops within the ventral mesogastrium. The part of the mesogastrium
between the stomach and liver forms the lesser omentum. The enlarging liver pushes the cardiac
end to the left of the midline.
 The spleen develops in the dorsal mesogastrium which becomes differentiated into 4 parts:
gastro-phrenic lig., gastro-splenic lig., lieno-renal lig. & greater omentum. The greater
omentum becomes redundant, enclosing the inferior recess of lesser sac between its anterior 2
layers and its posterior 2 layers. Later, adhesions occur, obliterating most of the inferior recess.
N.B.: Being derived from the fore-gut, the stomach is supplied by the coeliac trunk.
ANOMALIES:
1. Congenital hvpertrophic pyloric stenosis:
- Occurs more in boys especially the 1st born.
- Hypertrophy of the muscle of the pylorus  obstruction & vomiting.
2. Thoracic stomach & hiatus hernia: the whole stomach or part of it lies in the
thorax, due to short esophagus.
3. Reversed rotation as a part of situs inversus totalis.
4. Hour-glass stomach: constricted middle part.
SPLEEN
 Develops from the mesodermal cells of the left layer of the dorsal mesogastrium.
The cells proliferate forming separate nodules which fuse later forming a lobulated spleen.
Lobulation is evidenced by the presence of notches on the upper border of the mature spleen.
 The spleen is a hemopoietic organ in the fetus.
ANOMALIES: persistent fetal lobulation - accessory splenic nodules.
DUODENUM
 A U-shaped duodenal loop, which is convex forwards, develops from the
caudal part of fore-gut & the cranial part of the mid-gut. Just above the
junction of both parts, a liver bud arises from the convexity of the duodenal
loop. The whole loop is connected to the posterior abdominal wall by a
mesoduodenum. Also, the 1st inch is connected to the ventral mesogastrium.
 The duodenal loop rotates, with the stomach, 90º to the right until it rests on
the peritoneum of the posterior abdominal wall and fuses with it. The fused
peritoneal surfaces become absorbed, thus the duodenum becomes retro-
peritoneal except the 1st inch.
 The opening of the liver bud (the future opening of the common bile
duct) is shifted to the posteromedial aspect of the duodenal loop due
to unequal growth of its walls.
 The lumen becomes obliterated, by proliferation of its epithelial
lining, in the 6th week. Recanalization occurs in the 3rd month.
Blood supply & its relation to development:

 The part above the opening of the common bile duct is derived from the fore-gut; therefore,
is supplied by branches of the coeliac trunk.
 The part below the opening of the common bile duct is derived from the mid-gut; therefore,
is supplied by a branch of the superior mesenteric a.
ANOMALIES: atresia or stenosis due to incomplete recanalization.
LIVER & BILIARY SYSTEM

 A solid liver bud arises from the convexity of the duodenal loop at the
end of the fore-gut. Later it becomes canalized.
 The bud grows between the 2 layers of the ventral mesogastrium to reach
the septum transversum (ST) where it divides into 2 parts:
a. Pars cystica (small & caudal)  gall bladder & cystic duct.
b. Pars hepatica (large & cranial)  hepatic duct which divides into
right & left brs which break repeatedly into cords of hepatocytes.
The stem of the liver bud  the common bile duct.
 The mesoderm of the ST forms the capsule & stroma of the liver.
 The blood sinusoids of the liver develop from 2 sources:
a. Breakdown of vitelline veins by growing cords of hepatocytes.
b. Local angiogenesis from mesodermal cells within the ST.
Some lining cells  Von-Kupffer cells.
 In early fetal life, the liver is relatively large as it is a hemopoietic organ.
At first, the 2 lobes are equal. Later, the left lobe shrinks while the right lobe
grows more, exposing the bare area.
 Bile formation starts in 12th wk causing green colored fetal stools (meconium).
 The ventral mesogastrium becomes differentiated, by the growing liver, into:
a. Lesser omentum: between the liver and the stomach.
b. Falciform lig.: between the liver and the anterior abdominal wall.
c. Coronary & triangular ligaments (Rt. & Lt.): between liver & diaphragm.
ANOMALIES:
1. Variation in liver lobulation.
2. Agenesis of the gall bladder - Bifid, double or intrabepatic gall bladder.
3. Atresia of the common bile duct  jaundice.
PANCREAS
 Develops from 2 endodermal sources:
1. Ventral pancreatic bud from the liver bud.
2. Dorsal pancreatic bud from the concavity of duodenal loop.
 The ventral pancreas rotates to the concavity of the duodenal loop and fuses with the
dorsal pancreas within the mesoduodenum;
1. The ventral pancreas  most of the head +the uncinate process.
2. The dorsal pancreas  the rest of the pancreas.
 With rotation and absorption of the mesoduodenum, the pancreas becomes retro-
peritoneal.
 Early, the pancreas is drained by two ducts: dorsal & ventral.
Later, both ducts fuse & exchange parts so that
a. The distal part of the dorsal duct joins the proximal part of the ventral duct
forming together the main pancreatic duct which together with the common bile
duct  ampulla of Vater.
b. The remaining proximal part of the dorsal duct the accessory duct.
 Acini arise as buds that remain connected to the ducts while islets of Langerhans arise, in the 3rd
month, also as buds that disconnect from the ducts & secrete insulin in 5th month.
ANOMALIES:
1. Annular pancreas: a ring of pancreatic tissue encircling the duodenum.
2. Absence of ventral pancreatic duct: the sole dorsal pancreatic duct opens above the C.B.D.
3. Accessory pancreatic tissue in the stomach or intestine.
THE MIDGUT
 Forms a loop convex forwards having:
 2 limbs (cranial & caudal)
 Dorsal mesentery, containing the superior mesenteric artery
 An apex connected to the yolk sac by the vitellointestinal duct
 Later, a cecal bud appears in the beginning of the caudal limb.
 The following changes occur in the midgut loop:

1. Herniation & 1st rotation
 Occurs during the 6th week
 The elongating loop enters the umbilical cord as the abdominal cavity
becomes crowded by the growing liver.
 During herniation, the loop rotates 90° anticlockwise around the axis of the
superior mesenteric artery. As a result, the cranial limb becomes right and
the caudal limb left.
2. Reduction & 2nd rotation:
 Occurs during the 10th week due to:
1. Increased size of the abdominal cavity.
2. Decreased size of the liver.
3. Contraction of smooth muscles around the sup. mesenteric artery.
 The 1st part to return is the small intestine which passes to the left side of
the abdomen whereas the last part to return is the cecal bud which passes to
the right side of the abdomen, below the liver.
 180° anticlockwise rotation occurs during reduction. As a result:
1. The transverse colon crosses infront of the 2nd part of duodenum.
2. The sup. mesenteric a. crosses infront of the 3rd part of duodenum.
3. The cecum descends from its subhepatic position to the right iliac fossa. At
first, it is conical with the appendix arising from its apex. Later the opening of
the appendix shifts to the posteromedial aspect of the cecum, 1 inch below the
ileocecal valve.
4. The ascending colon becomes retroperitoneal by absorption of its mesentery
5. The intestine becomes obliterated then recanalized.
6. The vitellointestinal duct becomes absorbed in the 6th week.
ANOMALIES:
1. Congenital umbilical hernia: may be tied during ligation of the cord.
2. Abnormal rotation:
 Incomplete rotation (90° only)  rt. small intestine & lt. colon.
 Reversed rotation: transverse colon & sup. mesenteric a. behind the duodenum.
3. Congenital subhepatic cecum or apical appendix.
4. Persistent mesentery of ascending colon.
5. Atresia or stenosis of any part of the intestine.
6. Persistent remnants of the vitellointestinal duct:
 Meckel’s diverticulum: a blind pouch, 2 inches long, located 2 feet from the ileocecal
junction in 2% of people.
 Fecal fistula: connecting the ileum with the umbilicus.
 Vitelline cyst = persistent middle part of the duct.
THE HINDGUT
 The Cloaca:
- Is the dilated distal end of the hindgut.
- It is closed by the cloacal membrane and is connected to the umbilicus by the
allantois.
- In the angle between the allantois and the proximal part of the hindgut, the
mesoderm proliferates pushing the endoderm in the form of a growing coronal
partition called urorectal septum which divides the cloaca into a ventral
urogenital sinus and a dorsal rectoanal canal. The septum fuses with the
cloacal membrane dividing it into urogenital and anal membranes.
 The proctodeum:
- Is an ectodermal depression that develops below the anal membrane & forms
the lower part of the anal canal.
- The anal membrane ruptures establishing continuity between the endodermal
and ectodermal parts of the anal canal. The remnants of the anal membrane
form the anal valves. The 2 parts of the anal canal differ markedly from each
other regarding their nerve supply, blood supply, lymphatic drainage &
sensitivity to pain.
 Migrating neural crest cells invade the wall of hindgut forming autonomic
plexuses responsible for peristalsis.
ANOMALIES:
1. Rectal fistula: with the vagina in ♀or the urinary bladder in ♂.
2. Imperforate anus or rectal atresia.
3. Congenital megacolon (Hirshsprung disease): part of the colon lacks autonomic

plexuses (aganglionic segment); above this the colon is greatly distended.
DEVELOPMENT OF THE URINARY SYSTEM

THE KIDNEY
Three sets of kidneys appear successively in the intermediate cell mass mesoderm;
PRONEPHROS MESONEPHROS METANEPHROS

Time Beginning of 4th wk End of 4th wk In 5th wk
Site cervical region thoracic & upper lower lumbar and
lumbar regions sacral regions
Structure  7 tubules without 70 tubules with  Ureteric bud

glomeruli + glomeruli join the (collecting ducts)
 1 collecting duct mesonephric duct +
opening in the  metanephric cap
cloaca (1-3 million
tubules with
glomeruli)
Function not functioning in Functions transiently Functions during 2nd
humans ½ of pregnancy
Fate by the end of 4th wk, It is transformed to: Persists as the
the tubules disappear  Genital duct in ♂ permanent kidney
& the duct becomes  Vestigial
mesonephric duct remnants in ♀
FATE OF METANEPHROS:
I. The ureteric bud gives the collecting system:
 It arises as an outgrowth from the mesonephric duct, close to the
cloaca.
 Its cranial end penetrates the intermediate cell mass of mesoderm and induces it to form a
metanephric cap around it. This end dilates, forming the renal pelvis; which divides
continuously forming major calyces, minor calyces, papillary ducts of Billini & collecting
tubules. Approximately 1:3 million collecting tubules develop per kidney.
II. The metanephric cap gives the excretory system:

 The collecting tubules induce the cells of the metanephric cap to form renal
vesicles, which give rise to nephrons.
 One end of the nephron forms the Bowman's capsule that acquires a glomerulus of
capillaries. The other end communicates with one of the collecting tubules.
 Continuous lengthening of the tubule results in the formation of the proximal
convoluted tubule, the loop of Henle, and the distal convoluted tubule. At birth,
one to three million nephrons are developed per kidney.
III. Further changes occur to the developing kidney:

1. Shape; is lobulated at birth then becomes smooth.
2. Position; is initially in the pelvis, later ascends to the abdomen. This is caused by growth of
the body caudal to the kidneys which progressively occupy higher levels.
3. Blood supply; initially, from the median sacral artery then, from the common
iliac artery, then from the aorta.
4. Rotation; At first, its hilum looks forwards then it looks
medially.
FATE OF EXCRETED URINE:

The metanephros functions during the second half of pregnancy. Urine passes into the amniotic
fluid which is swallowed by the fetus, enters the intestinal tract, where it is absorbed into the blood
stream. It thus enters the placenta, which transfers metabolic waste products to the mother.
CONGENITAL ANOMALIES OF THE KIDNEY:

1. Renal Agenesis:
- Caused by early degeneration of the ureteric bud.
- If bilateral, the amount of amniotic fluid may be small (oligohydramnios).
The fetus is born alive but dies within a few days.
- If unilateral, it may be unnoticed until problems occur in the solitary kidney.
2. Congenital Cystic Kidney: Caused by failure of union between some
collecting and excretory tubules. The latter become distended by urine
forming cysts which may be numerous (polycystic kidney) or single
(solitary cyst).
3. Double kidney: Caused by early splitting of the ureteric bud on one
side. The metanephric tissue becomes divided into two parts forming two kidneys, each with its
own renal pelvis and ureter.
4. Pelvic Kidney: Caused by failure of one kidney to ascend through the arterial fork formed by
the umbilical arteries.
5. Horseshoe Kidney:
 Sometimes both kidneys are pushed so close together during their ascent & their lower poles
fuse resulting in the formation of a horseshoe kidney. The horseshoe kidney is
usually located at a lower level, since the root of the inferior mesenteric artery
prevents its ascent.
 The ureters emerge from the ventral aspect, as the fused kidneys fail to rotate.
6. Persistent Fetal Lobulation.
7. Aberrant Renal Artery(s): enters the kidney through one of its poles (usually the
lower pole) and not through its hilum.
THE URINARY PASSAGES
“Ureter - Urinary bladder – Urethra”
2 SOURCES:
1. The mesonephric duct:
The caudal part of the mesonephric duct (below the ureteric bud) is absorbed into the
ventral part of the cloaca to form the trigone of urinary bladder. As a result, the two
ureteric buds and the two mesonephric ducts open separately into the urinary
bladder.
2. The endodermal urogenital sinus:

The sinus is closed caudally by urogenital membrane & is connected to the
mesonephric ducts and the allantois (a process which extends to the umbilicus and umbilical
cord). It differentiates into 3 parts:
Fate in male Fate in female

Vesico- 1. the urinary bladder (except 1. the urinary bladder
urethral part the trigone) (except the trigone)
2. prostatic urethra above the 2. the whole urethra
ejaculatory ducts
Pelvic part 1. prostatic urethra below the Both form the vestibule
ejaculatory ducts of vulva, from which the
2. membranous urethra lower 2/3 of the vagina
Phallic part penile urethra except the part in arises as bud
the glans which is ectodermal
 The muscle of the bladder wall is derived from the

surrounding mesoderm.
 At birth, the urinary bladder is abdominal; it becomes pelvic
at puberty.
 The allantois constricts forming the urachus which connects the apex of the bladder with the
umbilicus. In adults, it gives the median umbilical ligament.
Anomalies of urinary bladder & ureter:
1. Ectopia vesica:
- The mucosa of the posterior bladder wall is exposed to the outside due to
absence of its anterior wall and the overlying anterior abdominal wall.
- Cause: deficiency of mesoderm in the anterior abdominal wall infront of the
bladder, with subsequent rupture of the bladder front and its covering ectoderm.
2. Patent Urachus:
a. Urachal fistula: urine drains from the umbilicus.
b. Urachal sinus: patent proximal or distal part of the urachus.
c. Urachal cyst: cystic dilation along the course of the urachus.
3. Recto-vesical fistula: caused by incomplete urorectal septum.
4. Double ureter & bifid ureter: caused by splitting of the ureteric bud
(completely or partially).
5. Ectopic ureter: the ureteric orifice opens into an abnormal site, for example:
- In males: the bladder neck, the prostatic urethra or the rectum.
- In females: the bladder neck, the urethra, the vagina, the uterus or the rectum
DEVELOPMENT OF THE GENITAL SYSTEM

GONADS
Indifferent Gonad:
1. Germ cells:
th
- Appear in the 4 week among the endoderm of the hindgut.
- They migrate by amoeboid movement along the dorsal
mesentery of hindgut to reach the site of the developing genital
ridges medial to the mesonephros.
- If germ cells fail to reach the ridges, the gonads do not develop. Hence, the
primordial germ cells have an inductive influence on its development.
2. The genital ridges:

- Appear in 6th week as a pair of ridges located on the medial sides of the
mesonephros, between it and the dorsal mesentery.
- The coelomic epithelium proliferates and its cells penetrate the
underlying mesoderm forming a number of solid cords, the primary sex
cords. In both male and female embryos these cords are connected to the
surface epithelium.
- Before the 7th wk., no sex cords are seen in the gonad & it is impossible to differentiate
morphologically between the male and female gonad, although the sex of the embryo is
determined since the time of fertilization.
TESTIS:
- If the embryo is a male the primordial germ cells carry XY sex chromosomes. A gene on the
Y chromosome, called the testis-determining factor (TDF), stimulates the undifferentiated
gonad to develop into a testis.
- The TDF induces the primitive sex cords to proliferate and penetrate deep into the medulla.
Near the hilum of the gonad, the cords break and anastomose into a network called rete
testis.
- Later, a dense layer of fibrous connective tissue, the tunica albuginea develops from the
surrounding mesoderm, isolating the testis cords from the surface epithelium.
- The cords become horseshoe-shaped and develop into the seminiferous cords that contain
two kinds of cells:
1. Primordial germ cells (endodermal)  Spermatogonia.
2. Supporting cells (mesodermal) Sertoli cells.
- The interstitial cells of Leyding develop from the mesoderm located between the cords.
During the eighth week, these cells begin to produce testosterone, which induces
masculine differentiation of the mesonephric ducts and the external genitalia.
- In addition to testosterone, the fetal testes produce mullerian-inhibiting factor (MIF) by
Sertoli cells. MIF suppresses development of the paramesonephric ducts.
- The cords become canilized at puberty to form the seminiferous tubules. which establish
open communication with the mesonephric tubules that form the vasa efferentia.
DESCENT OF THE TESTIS:

- The testis develops on the posterior abdominal wall opposite L1 vertebra, later it
descends to the scrotum pulling the testicular artery of the abdominal aorta.
- Caudal to the testis, a fibromuscular cord (the gubernaculum testis) passes
downwards obliquely through the developing anterior abdominal wall to reach the
genital (scrotal) swelling. The gubernaculum guides the testis during its descent.
- The testis descends in two stages:
o Internal descent:
 The testis reaches the deep inguinal ring in the 3rd month.
 Cause: relative elongation of the posterior abdominal wall in
an upward direction, without corresponding elongation of the
gubernaculum. Thus, it is a growth displacement rather than
active migration.
o External descent (through the inguinal canal):
 It starts in the 7th month & reaches the scrotum in the 8th month.
 Causes: Shortening of the gubernaculum due to atrophy of its
fibrous elements and contraction of its muscular elements (controversial).

- The processus vaginalis is a pouch derived from the coelomic cavity on
each side of the midline. It penetrates the anterior abdominal wall, running
ventral to the gubernaculum to reach the genital swellings. It pushes the
layers of the body wall forming the inguinal canal. The testis descends
dorsal to and outside the processus vaginalis.
 Its proximal part is obliterated  vestige.
 Its distal part is invaginated by the testis  visceral & parietal
layers of tunica vaginalis.
Testicular Anomalies:
1. Undescended Testis (cryptorchidism):
- Occurs in 3% of all full-term infants and 30% of premature infants. If a
testis fails to reach the scrotum within 3 months after birth, it remains
permanently high.
- If a testis is left within the abdomen, the high temperature destroys the
seminiferous tubules at puberty. If bilateral  sterility. However,
production of testosterone is normal, therefore, the accessory sex organs and
the secondary male sex characteristics develop normally.
- Undescended testis should be treated surgically because it has increased risk to develop
malignant tumors.
- Sites of undescended testis are: (1) Intra-abdominal,
(2) Inguinal canal,
(3) Superficial inguinal ring.
- In some cases, the testis can be pulled down by hand but when released, the cremaster
muscle immediately draws it up. This is called retractile testis & requires no treatment.
2. Maldescended Testis:
- the testis may be found at:
(1) root of the penis, (2) perineum,
(3) femoral triangle or (4) opposite side.
- The testis is pulled by abnormal tails of the gubernaculum.
- Maldescended testis should be treated surgically & placed in the
scrotum because it is liable to injury in this unprotected position.
3. Absent testis (Agenesis) or Double testis: unilateral or bilateral.
4. Hydrocele: collection of peritoneal fluid in the processus vaginalis that remains
connected to the peritoneal cavity by a narrow channel.
5. Congenital lnguinl Hernia: herniation of abdominal contents into a patent
processus vaginalis when its neck is wide enough.
6. Polycystic Testis:
- The rete testis fails to communicate with the vasa efferentia.
- If bilateral  sterility & azospermia, however sperms are found in
testicular biopsy.
OVARY:
- The primitive sex cords break into medullary cords which form a rudimentary
rete ovarii.
- The surface epithelium continues proliferation  a second generation of cords,
called cortical cords, which split into primordial follicle:

 The endodermal germ cells  oogonia. Active mitosis  daughter oogonia
(all oogonia are formed prenatally, many degenerate before birth). The two
million or so that remain enlarge  primary oocytes.
 The surrounding mesodermal cells, derived from the surface epithelium, the
follicular cells.
- After birth the surface epithelium  the "germinal epithelium" which has nothing to do
with germ cell formation. A thin, fibrous capsule, tunica albuginea, separates the surface
epithelium from the cortex.
DESCENT OF THE OVARY

- Is only internal due to growth displacement.
- It reaches the false pelvis in the 3rd month and the true pelvis shortly after
birth.
- As the ovary descends, it pulls the ovarian artery from the abdominal aorta.
- The suspensory ligament & mesovarium persist
- The gubernaculum becomes divided by the growing uterus into:
1. The ligament of the ovary
2. The round ligament of the uterus
- A small processus vaginalis is also formed in females. However, it becomes
obliterated and disappears after birth. If persists, it forms the canal of Nuck.
GENITAL DUCTS
The Indifferent Stage:
Both male and female embryos develop two pairs of genital ducts.
 Mesonephric (Wolffian) ducts:
Fate in male:
mesonephric tubules: give
1. vasa efferentia & head of epididymis.
2. Some embryonic remnants = superior aberrant ductule + inferior aberrant ductule
+ paradidymis.
mesonephric duct: give
1. body and tail of epididymis, vas deferens, seminal vesicle & ejaculatory duct
2. ureteric bud & trigone of urinary bladder.
3. appendix of epididymis.
Fate in female:
mesonephric tubules  embryonic remnants in broad lig. = epoophoron &
paroophoron
mesonephric duct  Gartner's duct + the ureteric bud and trigone
 Paramesonephric (Mullerian) ducts: give the female genital ducts.

- The paramesonephric duct develops lateral to the mesonephric duct as a
longitudinal groove (in-rolling) in the coelomic epithelium.
- The caudal end of the groove grows parallel to the mesonephric duct, as solid cord,
which later canalizes to form the paramesonephric duct. The funnel-shaped
cranial end of the duct remains open into the coelomic cavity, forming the
abdominal ostium.
- When the paramesonephric ducts reach the future pelvic region of the embryo, they turn
medially, crossing ventral to the mesonephric ducts, until they meet each other in the
median plane and fuse to form a Y-shaped uterovaginal canal which grows caudally to
reach the dorsal wall of the urogenital sinus.
Fate in male
1. Testosterone, secreted by the interstitial cells, stimulates growth of mesonephric ducts.
2. Mullerian-inhibiting factor (MIF), secreted by the Sertoli cells, suppresses development of
the paramesonephric ducts which degenerate except:
a. Its cranial end  the appendix testis (small vesicle on the upper pole of testis).
b. Its caudal end  the prostatic utricle (small diverticulum on the back of the prostatic
urethra, equivalent to the uterus and vagina in females).
Fate in female:
In female embryos, the mesonephric ducts regress due to the lack of testosterone, while the
paramesonephric ducts develop due to the absence of the mullerian inhibiting factor MIF 
most of the female genital tract:
 The cranial, unfused, parts form the Fallopian tubes. The cranial
ends of the original groove form the abdominal ostia & fimbria
develop around it.
 The caudal fused parts form the uterovaginal canal which gives
rise to the uterus and upper 1/3 of the vagina (the fornices). The
myometrium is derived from the surrounding splanchnic
mesoderm.
Vagina:
- At the site of the mullerian tubercle, two solid evaginations called
sinovaginal bulbs grow out from the urogenital sinus.
- They fuse forming a solid vaginal plate which grows cranially.
- It becomes canalized except a thin plate, known as the hymen, separating
the lumen of vagina from the urogenital sinus. It ruptures in its middle
during perinatal life.
Anomalies of paramesonephric ducts:
(1) Failure of fusion: takes variable forms
1. Double uterus and double vagina (uterus didelphys).
2. Double uterus and single vagina (uterus bicornis); one horn
may be rudimentary (uterus bicornis unicollis).
3. A septum in a single uterus (uterus septatus)
4. An indented fundus of uterus in the middle (uterus arcuatus)
5. Failure of fusion of the sinovaginal bulbs  double vagina
(2) Aplasia of one paramesonephric duct (uterus unicornis).
(3) Hypoplasia: A hypoplastic or infantile uterus has the ratio of its body: cervix reversed
(normally it is 2:1, in hypoplasia it is 1:2).
(4) Failure of canalization:
1. Atresia of the cervix or the vagina.
2. Imperforate hymen: passes unnoticed till puberty, when retention of menstrual blood in the
vagina  a painful
swelling (hematocolpos)
EXTERNAL GENITALIA
I. Indifferent Stage: 5 elevations develop around the urogenital membrane:

 1 genital tubercle cranially.
 2 genital (urethral) folds medially
 2 genital (labio-scrotal) swellings lateral to the urethral folds.
- Until the seventh week, it is impossible to distinguish between the two sexes.
II. Fate in the Female: in the absence of testosterone, female pattern occurs.
- The genital tubercle becomes small  the clitoris.
- The urethral folds remain separate  the labia minora.
- The genital (labial) swellings enlarge  the labia majora.
- The urogenital sinus opens to the surface  the vaginal vestibule.
III. Fate in the Male:

- Development is under influence of testosterone secreted by the fetal testes
- The genital tubercle elongates  the phallus; its distal part forms the glans
 The urethral folds extend forward on the under surface of the elongating phallus
forming the lateral edges of the urethral groove.
 The urethral groove, after rupture of the urogenital membrane, becomes lined
by endodermal cells creeping from the phallic part of urogenital sinus.
 The urethral folds fuse from behind forwards closing the penile urethra. The
urethral meatus opens on the under surface of penis opposite the root of glans.
 An ectodermal solid cord penetrates from the tip of the glans inward. Then it
obtains a lumen and communicates with the rest of the penile urethra, so that the
definitive external urethral meatus opens at the tip of the glans.
- The genital or scrotal swellings fuse incompletely  the scrotum, which has two
compartments separated by an incomplete septum.
Anomalies:
1. Hypospadias:
- The urethral meatus is found on the under aspect of the penis.
- Caused by incomplete fusion of the urethral folds.
- Types:
a. glandular (in the glans)
b. penile (along the shaft)
c. coronal (in-between)
d. penoscrotal (near base of penis)
e. perineal (along the scrotal raphe, between two scrotal swellings).
2. Epispadias:
- The urethral meatus is found on the dorsum of the penis.
- It is usually associated with ectopia vesica.
3. Divided or bifid penis: the two sides of the genital tubercle do not fuse.
4. Agenesis of penis or Micropenis.
ACCESSORY GLANDS:
Two sets of buds arise from the urogenital sinus in both sexes:
Derivative in males Derivative in females
Cranial buds (from prostatic glands urethral glands
pelvic part) (of Littre)
Caudal buds (from bulbo-urethral glands great vestibular glands
phallic part) (of Cowper) (of Bartholin)
The Prostate:
- 15-20 endodermal outgrowths from the prostatic urethra invade the surrounding mesoderm
 prostatic acini, arranged in 5 lobes.
- Surrounding mesoderm  stroma of prostate.
- Before birth, the prostate is large due to maternal hormones.
Hermaphrodite and Intersex:

1. True hermaphrodite = gonads & external genitalia of both sexes present in the same
individual. It is rare.
2. Pseudohermaphrodites = gonads of one sex & genitalia resembling the opposite sex. Two types
can be seen:
a. Male Pseudohermaphrodite: e.g. testicular feminization syndrome
- Patient has 44+ XY chromosomes but the appearance of normal female.
- Cause: tissues of external genitalia unresponsive to androgens produced by the testes
(lack androgen receptors).
- The uterine tubes and uterus are absent; the vagina is short and ends blindly. The testes
are frequently found in the inguinal or labial regions, but spermatogenesis does not occur.
b. Female Pseudohermaphrodite: adrenogenital syndrome and progesterone therapy
- Patient has 44 + XX chromosomes & ovaries; however excessive production of
androgens by the adrenals  male pattern of external genitalia, with large clitoris
resembling a penis & fused labia majora resembling a scrotum.
SUMMARY
Structure Fate in males Fate in females

Mesonephros:- Tubules: Epididymis + remnants Epoophoron & paroophoron
- Duct: Duct of epididymis + vas deferens + Gartner’s duct
seminal vesicle + ejaculatory duct.
Trigone + ureteric bud + back of Trigone & ureteric bud.
prostatic urethra above seminal
colliculus
Urogenital sinus:
Vesico-urethral part: Urinary bladder (except trigone) Urinary bladder (except trigone) +
+ upper ½ of prostatic urethra whole urethra
Pelvic part: Lower ½ of prostatic urethra + Vestibule + the lower 2/3 of
membranous urethra vagina)
Phallic part: Penile urethra (urethral plate) Vestibule
except part in glans
Glandular buds:
Cranial (from pelvic part) Prostatic glands Urethral glands (of Littre)
Caudal (from phallic part) Bulbo-urethral (Cowper) gld Great vestibular (Bartholin)
Indifferent gonad: Testis Ovary
Coelomic epithelium: Mesothelium Germinal epithelium
1ry (medullary) cords: Persist Degenerate  medulla
2ry (cortical) cords: Not formed Persist
Endodermal germ cells: Spermatogonia Oogonia  1ry oocytes
Mesodermal cord cells: Sertoli cells Follicular cells
Tunica albuginea: Thick Thin
Mesoderm: Cells of Leyding Stroma & theca cells
Gubernaculum: Disappears Lig. of ovary & of uterus
Processus vaginalis: Tunica vaginalis + vestige Disappears
Descent of gonad: Internal & external Internal
Communication with ducts occurs none
Genital Duct:
Paramesonephric duct: Appendix testis + prostatic utricle Fallopian tubes + uterus + vaginal
(!) fornices
Mesonephric duct: See above See above
External Genitalia:
Genital tubercle (phallus): Dorsum of penis + glans Clitoris
Genial (urethral) folds: Fuse raphe under penis Separated Labia minors
Genital (labioscroal) swellings: Fuse scrotum (with septum) Separated Labia majora

Development of The Limbs: Mesoderm and Migrating Myotomes

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Development of The Limbs: Mesoderm and Migrating Myotomes

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Prof.

Hany Shawky Nadim 1 Systemic Embryology

DEVELOPMENT OF THE LIMBS

 lnnervation of the limb buds:

DEVELOPMENT OF CARDIOVASCULAR SYSTEM

DEVELOPMENT OF THE HEART

FORMATION OF THE HEART TUBE (CARDIAC LOOP):

FATE OF THE SINUS VENOSUS

In Summary; each atrium is derived from 3 sources:

THE REMAINING CHAMBERS

Five septa divide these chambers

ANOMALIES OF THE HEART

(2) Septal Problems:

2. Ventricular Septal Defects (VSDs):

3. Abnormal division of the truncus arteriosus:

1. The arthe arch of aorta is derived from 3 sources:

III. Ventral splanchnic arteries:

DEVELOPMENT OF THE RESPIRATORY SYSTEM

Lung Maturation: it passes into 4 stages:

DEVELOPMENT OF THE GIT

mesogastrium, mesoduodenum, mesentery & mesocolon).

FATE OF THE GUT TUBE:

 The mucosa is derived from the endoderm of the gut tube.

Blood supply & its relation to development:

LIVER & BILIARY SYSTEM

 The following changes occur in the midgut loop:

2. Imperforate anus or rectal atresia.

3. Congenital megacolon (Hirshsprung disease): part of the colon lacks autonomic

DEVELOPMENT OF THE URINARY SYSTEM

PRONEPHROS MESONEPHROS METANEPHROS

Structure  7 tubules without 70 tubules with  Ureteric bud

II. The metanephric cap gives the excretory system:

III. Further changes occur to the developing kidney:

FATE OF EXCRETED URINE:

CONGENITAL ANOMALIES OF THE KIDNEY:

2. The endodermal urogenital sinus:

Fate in male Fate in female

 The muscle of the bladder wall is derived from the

DEVELOPMENT OF THE GENITAL SYSTEM

2. The genital ridges:

DESCENT OF THE TESTIS:

fibrous elements and contraction of its muscular elements (controversial).

called cortical cords, which split into primordial follicle:

DESCENT OF THE OVARY

 Paramesonephric (Mullerian) ducts: give the female genital ducts.

I. Indifferent Stage: 5 elevations develop around the urogenital membrane:

III. Fate in the Male:

Hermaphrodite and Intersex:

Structure Fate in males Fate in females

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