M1SDemb: Embryology

Embryological development can be divided into 3 main stages:

1. Early Development (1st to 3rd week): Fertilisation, Implantation, Gastrulation
2. Embryonic Period (4th to 8th week): Differentiation, Organogenesis
3. Fetal Period (9th week to 9th month): Growth and Specialisation of the fetus

1. Early development

Week 1
Embryoblast Trophoblast
(Inner cell mass)
Once the ovum has been fertilized by
the spermatozoon, a zygote (single A (Outer
Blastocoele cell mass)
Blastocyst
cell) is formed. This undergoes a rapid
succession of mitotic divisions
(cavity)
(cleavage) without an increase in size,
forming blastomeres, and eventually a
morulla (12-32 blastomeres).
- A hollow cavity (blastocoele) forms at around day 3, marking the
blastocyst stage.
- The centrally placed cells are called inner cell mass (embryonic pole, or
embryonic stem cells) and ultimately form tissues of the embryo
(embryoblast).
- The outer cells, called the outer cell mass, form the trophoblast, which
plays an important role in the formation of the placenta and the embryonic
membranes.

At around days 5-6, implantation of the blastocyst on the endometrial lining of

the uterus occurs.

Ectopic Pregnancy
An ectopic pregnancy is a complication of pregnancy in which the fertilized ovum
is implanted in any other tissue other than the uterine wall. Most ectopic
pregnancies occur in the Fallopian tubes (tubal pregnancy), but implantation
can also occur in the cervix (placenta praevia), ovaries, internal os, or
abdominal cavity. The fetus produces enzymes that allow it to implant in varied
types of tissues, and thus an embryo implanted elsewhere than the uterus can
cause great tissue damage in its efforts to reach a sufficient supply of blood.

Week 2
Syncytiotrophoblast
Trophoblast cells surrounding

deeper into the uterine lining.

the
embryonic cells proliferate and invade Epiblast
Amniotic cavity
Differentiation of the cell masses occur:
- Embryoblast (ICM) differentiates to Primitive yolk sac
form the epiblast and hypoblast.
- Trophoblast cells (OCM)
Hypoblast
Cytotrophoblast
differentiates to form the
cytotrophoblast and
syncytiotrophoblast.

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Movement of the hypoblast laterally and downwards forms the primitive
yolk sac; and the amniotic cavity, between the epiblast and amnioblast
occurs.

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Week 3
Gastrulation occurs, in which distinct
layers are formed from within embryo,
which will later grow into different organs.
The epiblast (embryonic cells) flattens into
a bilaminar embryonic disc, composed of
2 germ layers: the upper ectoderm and the
lower endoderm.

As growth proceeds, the embryonic disc becomes pear-shaped, and a narrow

streak appears on its dorsal surface formed of ectoderm, called the primitive
streak. The further proliferation of the cells of the primitive streak forms a layer
of cells that will extend between the ectoderm and the endoderm to form the
mesoderm.

Further thickiening of the ectoderm gives rise to the neural plate on the dorsal
surface of the embryo. The plate sinkw beneath the surface of the embryo to
form the neural tube, which ultimately gives rise to the CNS.

A notochord, derived from mesoderm, forms in the centre of the embryonic

disc and on the ventral surface of the neural tube. This notochord will
eventually develop to form the vertebral column.

The primitive yolk sac becomes modified to become the secondary yolk sac,
while a chorionic cavity develops between the 2 layers of mesoderm.
Eventually, the placenta develops.

Embryonic Period
The initially flat embryonic disc develops into a
C-shaped cylindrical structure. A
Cephalocaudal flexion (in the longitudinal
Amniotic cavity sac
Yolk
direction) and lateral folding (in the
transversal folding) occur simultaneously,
A
forming the abdominal wall, permitting a
delimitation of the embryo. This also leads to
Y
enclosure of mesoderm and endoderm by Y A
the ectoderm, which later forms the
epidermis.

Neurulation, development of the CNS, also Y

occurs.

Derivatives of the Germ layers

Ectoderm Mesoderm Endoderm
Epidermis: Connective Tissue, Epithelium of Digestive
Hair, Nails, Sebaceous Cartilage, Bones and tube:
Glands Joints Foregut, Midgut, Hindgut
CNS: Brain and Spinal Walls of Heart Parenchyma of
Cord Digestive tube:
PNS Muscles: Tonsil, Thyroid,
Smooth, Striated and Parathyroids, Thymus,
Cardiac Liver, Pancreas
Sensory epithelium of Urogenital System:
sense organs Kidneys, Gonads and

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 Inner ear their Ducts, Suprarenal Epithelium of
Cortex Respiratory Tract:
Eye (lens) Mesothelium (Serous Lungs
Pituitary gland membranes): Pleura, Middle Ear (Tympanic
(hypophysis) Pericardium, Peritoneum Cavity and Eustachian
Teeth (enamel) tube)
Epithelium of some Blood and Lymph cells Part of Bladder and
organs Urethra

Fetal Period
The foetal period (9th week to 9th month) is about continued differentiation of
organs and tissues, most importantly this period is about growth both in
size and weight.

Organogenesis
- Early development: Any organ develops from a primordium (bud) derived
from one or more germ layers found in the germ disc during early
development.
- Embryonic period: After folding is completed, the primordial of many organs
become easily recognizable as a simple shape. Primordium undergoes
changes in shape, size and site to become anatomically recognizable.
- Fetal period: Differentiation of cells in the developing organ into specific
cell types help with maturation whereby the organ becomes capable of
normal function.

Development of the Lungs and Pleura

Germ layer:
- Lungs: Endoderm Ventral wall of primitive foregut
- Pleura: Mesoderm surrounding diverticulum
Primordium: Laryngotracheal diverticulum

Embryonic Period
1. The diverticulum is partially partitioned off by the formation
of the tracheoesophagal septum from the
tracheoesophagal ridges/grooves on either side. This
divides the foregut into the laryngotracheal tube (ventral)
and the esophagus (dorsal).
2. The partitioned portion of the laryngotracheal diverticulum
separates off by splitting along the septum from the
esophagus. The caudal end enlarges to form the lung
bud, which is surrounded by splanchnic mesoderm.
3. Several generations of branching progressively increases the surface
area for gas exchange. This branching takes place mostly dichotomously
except after the formation of the primary when the R. divides into 3 and L.
into 2. By the end of the embryonic period, the lungs have the correct
appearance but are still immature.

Fetal Period
- Cells lining terminal sacs become progressively flattened (increase
efficiency of gas exchange)
- Rich vasculature develops around the terminal sacs (increase perfusion of
alveoli)

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- Type 2 cells in terminal sacs secrete increasing amounts of surfactant
(reduces surface tension in the fluid in the sacs to facilitate easy
expansion of lungs at birth. Hence premature birth predisposes to
respiratory distress syndrome)
- Endodermal cells differentiate into respiratory epithelium and glands
- Mesodermal cells give rise to cartilaginous plates, smooth muscles and
connective tissue.
o Splanchnic mesoderm forms visceral pleura
o Somatic mesoderm forms parietal pleura

Esophageal atresia and Tracheoesophagal Fistula

Atresia is a condition where the laryngotracheal septum formed by fusion of the
laryngotracheal ridges are deviated posteriorly, resulting in a reduced lumen
diameter; while a fistula results when the margins of the laryngotracheal
ridges fail to fuse adequately, resulting in an abnormal opening left between
the laryngotracheal tube and the esophagus. Newborn infants with these
malfunctions cough and choke during eating due to aspiration of food and
saliva into lungs due to blocked esophagus, and may result in pneumonia.
Development of the Diaphragm

Germ Layer: Mesoderm formed in neck by fusion of myotomes of 3rd, 4th and
5th cervical segments. Hence, the diaphragms nerve supply is derived from
the phrenic nerve (C3, C4, C5).
Primordium: Septum Transversum An incomplete mesodermal partition on
ventral aspect of embryo caudal to developing heart. The incompleteness is due
to 2 pleuroperitoneal canals dorsal to it (one on each side) which allows
communication between the pleural and peritoneal cavities.

The diaphragm is formed from:

1. Septum Transversum: Forms the muscle and central tendon
2. 2 Pleuroperitoneal membranes: Forms peripheral areas of diaphragmatic
pleura and peritoneum covering its upper and lower surfaces
3. Dorsal meso-esophagus: Forms crura

Development
1. Pleuroperitoneal folds develop from the dorsolateral body wall growing
ventromedially to fuse with the septum transversum and the dorsal
meso-oesophagus, thereby forming the pleuroperitoneal membranes.
This effectively closes the pleuroperitoneal canals.
2. The developing lungs growing caudally (especially at the periphery) helps
add the peripheral portions of the diaphragm from the body wall, as
well as create the dome shape. Hence, the periphery of the diaphragm
shares nerve supply with the thoracic nerves.
3. Progressive caudal migration of the diaphragm results in the phrenic nerve
taking a course more in line with the body axis.

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Diaphragmatic Hernia
Congenital hernia can occur as the result of
incomplete fusion of the 3 components. Abdominal
contents can then be pushed up through the hiatus
into the thoracic cavity. The herniae occur at the
following sites:
- Pleuroperitoneal canal (caused by incomplete
fusion of pleuroperitoneal folds with septum
transversum)
- Opening between xiphoid and costal origins of the
diaphragm
- Esophageal hiatus

Development of the Cardiovascular System

Germ Layer: Mesoderm

Primordium: Endocardial Heart Tubes

Formation of the Heart Tube

Clusters of cells arise in the mesenchyme
(mesoderm) at the cephalic end of the embryonic
disc, cephalic to the site of the developing mouth and
CNS. They form a plexus of endothelial blood
vessels that fuse to form the R. and L. endocardial
tubes, which soon fuse to form a single median
endocardial tube. As the head fold of the embryo
develops, the endocardial tube and pericardial cavity
rotate on a transverse axis through almost 180
to come ventral to the esophagus and caudal to
the developing mouth.
The heart tube starts to bulge into the pericardial
cavity. Meanwhile, the endocardial tube becomes
surrounded by a thick layer of mesenchyme,
which will differentiate into myocardium (cardiac
muscle) and visceral layer of the serious
pericardium. The primitive heart has been
established, and the cephalic end is the
arterial end and the caudal end is the venous
end. The arterial end is continuous beyond the
pericardium with a large vessel, the aortic sac.

Further development of the heart tube

The heart tube then undergoes differential
expansion so that several dilatations, separated
by grooves result. From the arterial to venous end,
these dilatations are the bulbus cordis,
ventricle, atrium, and the R. and L. horns of
the sinus venosus. The bulbus cordis and
ventricle elongate and bend, finally forming a
compound S-shape, such that the atrium lies
posterior to the ventricle. The passage
between the atrium and ventricle narrows to form

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the atrioventricular canal. A gradual migration of the heart tube occurs so
that the heart passes from the neck to the thoracic region.

Development of the Atria

1. Atrioventricular canal becomes divided into R. and L. halves by
appearance of ventral and dorsal atrioventricular cushions, which fuse
to form the septum intermedium

2. A septum primum develops from the roof

of the primitive atrium and grows down to
fuse with the septum intermedium. The
opening between the lower edge of the
septum primum and the septum
intermedium is the foramen primum.

3. Before total obliteration of the foramen

primum has taken place, degenerative
changes occur in the central portion of
the septum primum, such that a foramen
secundum appears, so that the atrial
chambers can communicate again.

4. A thicker septum secundum grows down

from the atrial roof on the R. side of the
septum primum. The lower edge of the
septum secundum overlaps the foramen
secundum in the septum primum but does
not reach the atrial floor and does not
fuse with the septum intermedium. The space between the free margin of
the septum secundum and septum primum is the foramen ovale.

5. Before birth, the foramen ovale allows oxygenated blood that has entered the
R. atrium from the IVC to pass into the L. atrium. At birth, however, owing to
the raised BP in the R. atrium, the septum primum is pressed against the
septum secundum and fuses with it, and the foramen ovale is closed,
separating the atria. The lower edge of the septum secundum seen in the R.
atrium becomes the annulus ovalis, and the depression below this is the
fossa ovalis. The R. and L. auricles later develop as small diverticula from
the R. and L. atria.

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Development of the Ventricles
1. A muscular ventricular septum projects
upward from the floor of the primitive ventricle.
The space bounded by the upper edge of the
septum and the septum intermedium is the
interventricular foramen.
2. Bulbar ridges (spiral endocardial thickenings)
appear in the distal part of the bulbus cordis
grow and fuse to form a spiral
aorticopulmonary septum. The proliferation
of bulbar edges and septum intermedium
results in the closure of the interventricular
foramen.
3. The aorticopulmonary septum grows down and
fuses with the upper edge of the muscular
ventricular septum to form the membranous
part of the septum. This effectively shuts off
interventricular communication; while ensuring
R. ventricular communication with the
pulmonary trunk and L. ventricular
communication with the aorta.

The truncus arteriosus (distal part of bulbus cordis) is divided by the spiral
aorticopulmonary septum to form the roots and proximal portions of the aorta
and pulmonary trunk. The proximal portion of the bulbus cordis becomes
incorporated into the R. ventricle as the conus arteriosus/infundibulum; and
into the L. ventricle as the aortic vestibule. Two coronary arteries arise just
distal to the aortic valves.

Atrial Septal Defects

In 25% of hearts, the foramen ovale persists. Oxygenated blood from the L.
atrium passes over the R. atrium, decreasing the efficiency of circulation.

Ventricular Septal Defects

This occurs when the fusion between the membranous and muscular parts of the
ventricular septum is incomplete. Blood under high pressure passes through the
defect from L. to R., causing enlargement of the R. ventricle.

Tetralogy of Fallot
This occurs when the bulbar ridges fail to fuse correctly to form the
aorticopulmonary septum, resulting in unequal division of the bulbus cordis, and
consequent narrowing of the pulmonary trunk resulting in interference with R.
ventricular outflow. The anatomic abnormalities include large ventricular septal
defect; stenosis of pulmonary trunk; exit of aorta immediately above the
ventricular septal defect; and severe hypertrophy of the R. ventricle.

Embryonic Adult Structure

Dilatation
Sinus Smooth part of right atrium (sinus venarum),
venosus coronary sinus, oblique vein of left atrium
Primitive Trabeculated parts of right and left atria
atrium
Primitive Trabeculated parts of right and left ventricles
ventricle

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 Embryonic Adult Structure
Dilatation
Bulbus cordis Smooth part of right ventricle (conus
arteriosus), smooth part of left ventricle
(aortic vestibule)
Truncus Aorta, pulmonary trunk
arteriosus
Development of the GIT
The components of the GIT develop from the
primitive gut which is an endodermal tube
surrounded by mesoderm resulting from
folding of the trilaminar germ disc.
- Endoderm: Gives rise to lining
epithelium and parenchyma of glands
in the form of tubular outgrowths (e.g.
liver, pancreas)
- (Splanchnic) Mesoderm: Differentiates
into muscular wall (typical 4 layers),
blood vessels and connective tissue in
gut wall.

The 3 main subdivisions, from cranial to

caudal, are foregut, midgut (opposite yolk
sac) and hindgut.

Most of the primitive have a dorsal mesentery (mesogastrium, mesentery,

mesocolon). From the dorsal aorta in the midline, 3 main branches of arteries
(celiac, sup. mesenteric, inf. mesenteric) run down the mesentery to supply the
foregut, midgut and hindgut respectively. A ventral mesentery mostly
disappears soon after formation, except in relation to the stomach and liver.

Development of the Stomach

Germ layer:
- Stomach Walls: Endoderm of
primitive foregut
- Greater momentum: Mesoderm
Dorsal and Ventral Mesentery
Primordium: Fusiform swelling
(dilatation in caudal part of foregut, dorsal
to septum transversum)

1. With growth of the foregut, the

primitive stomach grows caudally
into the abdominal cavity and acquires
a ventral mesogastrium. Insufficient
movement may result in a hernia.

2. Besides showing increased growth over the dorsal aspect, the stomach
undergoes rotation through a longitudinal axis resulting in a change of
position of the closely related vagus nerves. Rotation through a
ventrodorsal axis moves the caudal end (pylorus) of the stomach to the
right. The L. vagus nerve now lies on the anterior surface of the

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 stomach. Excessive development of muscle in the pylorus results in
hypertrophic pyloric stenosis where food is unable to leave the stomach,
leading to projectile vomiting.

3. The dorsal mesogastrium grows and projects sac-like towards the left-side
and helps form the lesser sac of the peritoneal cavity and the greater
omentum in its caudal part.

4. Portions of the dorsal mesogastriun

(cranial part) depending on their
connections are referred to as the
gastrosplenic and splenorenal
ligaments.

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Development of Liver

Germ Layer: Endoderm of distal end of ventral foregut

Primordium: Liver Diverticulum (Hepatic bud)

1. The liver diverticulum appears on the ventral side of the foregut just
caudal to the septum transversum. It forms the gall bladder component
(cystic) caudally and the liver (hepatic) component cranially.
2. The hepatic part grows into the septum transversum and divides in a
dichotomous fashion repeatedly. The terminal (distal) parts of this
branching system differentiate into the hepatocytes, which secrete bile
into the more proximal parts which will form the bile ducts.
3. As the liver becomes too large for the septum transversum, it grows out
caudally into the abdominal cavity and separates the ventral
mesogastrium into the falciform ligament and the lesser omentum.

Biliary Atresia
Failure of the bile ducts to canalize during development causes atresia (lack of a
lumen). Jaundice soon appears after birth; clay-coloured stools and very dark
coloured urine is produced.

Development of the midgut

The duodenum (except 1st part),
jejunum, ileum, ascending colon and
proximal of the transverse colon are
developed from the midgut. Destined to
develop into the longest segment
of the gut, the midgut undergoes
rapid elongation during the
embryonic period.

1. Loop formation
2. Coiling (cranial segment)
3. Physiological Herniation with associated
90 counterclockwise rotation. This occurs in the umbilical cord which
contains a space that is a continuation of the primitive peritoneal cavity.

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4. Return to the abdominal cavity along
with a further 180
counterclockwise rotation.
This results in the sup. mesenteric
artery occupying a position
between the duodenum and
the transverse colon.
5. Fixation: Parts of the original
mesentery (all midgut viscera
except transverse colon)
become attached to the posterior
abdominal wall, rendering these associated segments
retroperitoneal.
6. Vitellointestinal duct is obliterated.

Potential Complications
1. Failure to return will result in hernia in the
umbilical region
2. Incomplete rotation (e.g. during return will result in coon being
on the left side). Abnormal adhesions form, which run across the anterior
surface of the duodenum and cause obstruction in the second part.
3. Reverse rotation (i.e. clockwise) results in duodenum lying anterior to the
transverse colon. Also causes duodenal obstruction, leading to vomiting.
4. Inadequate fixation gives abnormal motility to the gut which could predispose
to complications like volvulus (a loop getting twisted around itself and
getting strangulated)

Meckels Diverticulum
This represents a persistent portion of the vitellointestinal duct. It may possess a
small area of gastric mucosa, and bleeding may occur from a gastric ulcer in
its mucous membrane. Moreover, the pain from this ulcer may be confused with
pain from appendicitis. Should a fibrous band connect the diverticulum to the
umbilicus, a loop of small bowel may become wrapped around it, causing
intestinal obstruction.

Development of the Pancreas

Germ layer: Endoderm of the caudal end of the dorsal and ventral
foregut
Primordia: Dorsal and Ventral Diverticula
- The ventral diverticulum which appears immediately caudal to the liver
diverticulum.
- The dorsal diverticulum is located slightly cranial to the ventral
diverticulum.

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1. Both diverticula grow and branch repeatedly to
give rise to glandular portions more distally
and ducts more proximally to the gut. The
endocrine portions arise from the most peripheral
branches by budding off.
2. The ventral pancreas, with its duct and the
common bile duct associated with it, migrates
around the right side of the duodenal loop to
a position on the concave aspect of the duodenum
just caudal to the dorsal pancreas. Hence, the
duct of the ventral pancreas opens into the
duodenum just below that of the dorsal pancreas.
3. The common bile duct is brought to the R. side of the duodenum by
this migration. When the duodenum turns to the right to become
retroperitoneal, the common bile duct lies posterior to the proximal part
of the duodenum. This also explains why the ventral pancreas lies
posterior to the sup. mesenteric artery.
4. The ducts of the 2 glands become connected
and the final main pancreatic duct is derived from
the proximal ventral and distal dorsal pancreatic
ducts and the connecting portion. The proximal
dorsal pancreatic duct remains as the
accessory pancreatic duct.

The duodenum develops from the caudal end of the

foregut as well as the cranial-most part of the midgut;
hence its blood supply is from both the celiac trunk
(splenic artery and hepatic artery --- sup.
pancreaticoduodenal branch) and the sup.
mesenteric artery (inf. pancreaticoduodenal branch)

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Development of the Kidney

Germ layer: Intermediate mesoderm along posterior wall

of abdominal cavity
Primordium: Metanephric diverticulum and metanephric
mass

The kidney develops from 3 different, slightly overlapping

systems (from cranial to caudal):
- Pronephros: Rudimentary and non-functional. Consist of 7-10 solid cell
groups in the cervical region and forms nephrotomes (vestigial excretory
units) at the beginning of the 4 th week. Earlier groups of cells regress before
more caudal groups are formed. By the end of the 4 th week, the pronephros
disappears.

- Mesonephros: Functions for a short time in early

foetal life. The mesonephros and mesonephric
ducts are derived from the upper thoracic to
upper lumbar (L3) segments. In the middle of
the 2nd month, the mesonephros forms a large
ovoid organ on each side of the midline (with the
developing gonad lying on the medial side).
o Mesonephric ducts: The first excretory
tubules of mesonephros appear early in the
4th week. The tubules acquire a glomerular
capillary tuft at the medial end and
enter the longitudinal mesonephric
(Wolffian) duct at the lateral end. Cranial
tubules start degenerating while caudal
tubules are still differentiating, but most of them disappear by the end
of the 2nd month.

- Metanephros: Forms the permanent kidney. It appears in the 5 th week and

becomes functional at the end of the 1 st trimester. However, it is not
responsible for excretion of waste products, which is achieved by the
placenta. Urine passed into the amniotic cavity mixes with the amniotic fluid
and is swallowed by the fetus to enter the intestinal tract and absorbed by
the bloodstream. The process then repeats.
o Nephrons (the excretory system) develop from the metanephric
mesoderm in a similar way as the mesonephric system. The
mesodermal intermediate cell mass of the lower lumbar and
sacral regions develops into the metanephric tissue cap. Upon
contact with the elongating ureteric bud, it is induced to condense
around the ureteric bud, forming small renal vesicles, and becoming
comma-shaped bodies, followed by S-shaped bodies, and finally
metanephric tubules.
The proximal end forms the Bowmans capsule, which is
deeply indented by glomerulus
The distal end is in open connection with collecting tubules.
As the nephron lengthens, the PCT, DCT, and LoH develops.

There is no increase in number of nephrons post-natally. The kidneys

were lobulated at birth, but the lobulation disappears with growth of
nephrons.

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15
 o The collecting system develops from the ureteric
bud, an outgrowth of the mesonephric duct. The bud
penetrates metanephric tissue, dilating to form the
renal pelvis and the branches repeatedly, into the
major and minor calyces and finally the collecting
tubules.

Ascent of kidneys
The kidneys were initially located in the pelvic region and
supplied by the pelvic branch of the aorta. However, due to
diminution of body curvature and growth of body in the
lumbar and sacral regions, the kidneys shift to a more
cranial position in the abdomen and becomes supplied by the
arteries originating from the abdominal aorta. The lower
vessels then degenerate.

Renal Agenesis
This condition refers to the failure of development of one or both kidneys.
- Unilateral renal agenesis: Usually not of any major
concern as long as the other kidney is healthy.
However, people with this condition have considerably
higher chances of hypertension.
- Bilateral renal agenesis: The absence of kidneys
causes a deficiency of amniotic fluid (oligohydramnios)
in pregnant women. Normally, the amniotic fluid acts
as a cushion for the developing fetus. Insufficient
amniotic fluid may result in compression of the fetus,
resulting in further malformations. Most infants that
are born alive do not live beyond 4 hrs.

Ectopic/Pelvic Kidney
The kidney is arrested in some part of its normal ascent and usually
found at the pelvic brim. Such a kidney may present with no signs or
symptoms and may function normally. However, should it be inflamed, it may,
because of its unusual position, give rise to a mistaken diagnosis.

Horseshoe Kidney
This condition is the result of the fusion of the
caudal ends of both kidneys as they develop.
Both kidneys commence to ascend from the pelvis,
but the interconnecting bridge becomes trapped
behind the inf. mesenteric artery so that the
kidneys come to rest in the low lumbar region.
Both ureters are kinked as they pass inferiorly
over the bridge of renal tissue, producing urinary
stasis, which may result in infection and stone
formation. Surgical division of the bridge
corrects the condition.

Duplications of urinary tract / Double Pelvis / Bifid ureter

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Double pelvis of the ureter is usually unilateral. The
upper pelvis is small and drains the upper group of
calyces; the larger lower pelvis drains the middle and
lower groups of calyces. This cause is a premature
division of the ureteric bud near its termination. In bifid
ureter, the ureters may join in the lower 3 rd of their
course, may open through a common orifice into the
bladder, or may open independently into the bladder. In
the latter case, one ureter crosses its fellow and may
produce urinary obstruction.

Ectopic ureter
Instead of opening into the bladder, the ureter may open into the urethra, vagina
or uterus. The result is constant dribbling of urine (urinary incontinence).

Supernumerary Renal Arteries

These arteries represent persistent
fetal renal arteries, which grow in
sequence from the aorta to supply the
kidney as it ascends from the pelvis.
They may cross the pelviureteral
junction and obstruct the outflow of
urine, producing dilatation of the
calyces and the pelvis, known as
hydronephrosis.

Development of the Bladder and Urethra

A urorectal septum divides the cloaca into the

anorectal canal and urogenital sinus between the 4th
and 7th weeks. The cloaca membrane is divided into the
urogenital membrane and the anal membrane.

The urogenital sinus has 3 portions:

- Vesical part: This is the largest part of the urogenital
sinus and forms the urinary bladder. It is initially
continuous with the allantois, which will eventually be
obliterated to form a thick fibrous cord called the
urachus, which eventually forms the median umbilical
ligament, connecting the apex of the bladder with the
umbilicus.
- Pelvic part: This is a narrow canal which forms the
prostatic and membranous parts of the urethra in males.
- Phalic / Definitive part: This part is flattened from side to side, and is
separated from the exterior by the urogenital membrane.

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The caudal end of the mesonephric duct is absorbed into the developing
bladder and forms the trigone and part of the urethra (in males, the
prostatic urethra). In the male, the cranial end of the mesonephric duct is
joined to the developing testis by the efferent ductules of the testes, and so it
becomes the duct of the epididymis, the vas deferens and the ejaculatory
duct. In the female, the mesonephric duct largely disappears. Only small
remnants persist as the ducts of the epoophoron and paroophoron.

The mucosa of the bladder is formed by incorporation of the mesonephric

ducts and ureters in the trigone region, and is hence of mesodermal origin.
However, the mesodermal lining is replaced by endodermal epithelium with
time, and eventually, the entire bladder is lined by epithelium of endodermal
origin.

The urethra is of endodermal origin from the urogenital sinus. In males, the
distal (penile) part is derived from the urethral plate. The surrounding connective
tissue and smooth muscle tissues are derived from splanchnic mesoderm.

Development of the Reproductive Systems

Genetic sex is determined at fertilization. It is the Y

chromosome which is key to sexual dimorphism. In males,
the SRY (sex-determining region on Y) gene located on Yp11
encodes a testis-determining transcription factor that
initiates male sex determination. Females have an XX sex
chromosome complement, without a Y chromosome or testis-
determining factor.

Indifferent Gonads (Common to both males and

females)
Like the kidneys, the indifferent gonads develop from the
intermediate mesoderm along the posterior wall of the abdominal cavity. The
gonads appear initially as longitudinal gonadal ridge, medial to the urogenital
ridge.

Primordial germ cells appear among endoderm cells in the wall of the yolk
sac close to the allantois. They migrate along the dorsal mesentery of the hind
gut to arrive at the primitive gonads at the beginning of the 5 th week, invading
the gonadal ridges in the 6th week. If germ cells are absent, gonads do not
develop.

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The epithelium proliferates and
penetrates the condensed
mesenchyme (mesoderm) to form the
primitive sex cords, which are connected
to the surface epithelium.

----------------------------------------------------------------

Testis
Under the Y chromosome influence (SRY gene), the primitive sex cords
proliferate and penetrate deep into the medulla to form the testis/medullary
cords.

The testis cords develop and become horseshoe shaped in the 4 th month. They
comprise primitive germ cells and sustentacular/Sertoli cells derived from
the gonadal surface epithelium. Meanwhile the cords near the testis hilum
break up to form the rete testis, a network of tiny cell strands. At puberty, the
solid testis cords acquire a lumen to form seminiferous tubules which connect
to the rete testis. The mesenchyme of the gonadal ridge develop shortly
after the onset of testis cord differentiation to form the interstitial Leydig cells
which lie between the testis cords. These cells produce testosterone from the
8th week onwards to influence differentiation of genital ducts and external
genitalia.

Ovary
The primitive sex cords dissociate into irregular cell clusters containing groups of
primitive germ cells and occupy the medullary part of the ovary. The medullary
cords later disappear, and are replaced by vascular stroma to form the
ovarian medulla.

The surface epithelium continues to proliferate to give rise to secondary

cortical cords at the 7th week. They penetrate the underlying mesenchyme
and split into isolated cell clusters, each surrounding 1 or more primitive germ
cells. The germ cells develop into oogonia; while the surrounding epithelial cells
form follicular cells.

-------------------------------------------------------

Descent of the testis

The gubernacula, which are folds of mesenchymal tissue/peritoneum
attached to the caudal end of the testis, aid in the descent of the testis. It

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extends to the inguinal region
between the internal and external
oblique muscles, and forms an extra-
abdominal portion extending
towards the scrotal swellings.

As the testis descends behind the

peritoneum, it drags along the
fascia/muscles in its course:

Origin Structure
Processus Parietal and visceral
vaginalis layers of tunica
vaginalis
Transversalis Internal spermatic
fascia fascia
Int. oblique Cremasteric fascia
and muscle
Ext. oblique External spermatic
fascia
Transversus (does not cover path
abdominis of migration)

The processus vaginalis is an

evagination of peritoneum into
the ventral abdominal wall. It
follows the course of the
gubernaculums into the scrotal
swellings and forms the inguinal
canal together with the muscular and fascial layers of abdominal wall. Its
connection with the peritoneal cavity is obliterated at or shortly after birth.

The descent of the testis is controlled by the outgrowth or regression of the

extra-abdominal portion of the gubernaculums, increase in intra-abdominal
pressure due to organ growth and hormonal influences, e.g. androgens and
Mullerian-inhibiting substances.
Congenital Inguinal Hernia
This occurs when the processus vaginalis is unobliterated, and intestinal
loops descend into the scrotum via the inguinal canal from the deep
inguinal ring through the superficial ring. The remains of the processus vaginalis
form the hernial sac.

Hydrocele of testis and/or spermatic cord

The processus vaginalis may become very much narrowed but not
completely obliterated; hence its lumen remains in communication with the
abdominal cavity. Peritoneal fluid accumulates in it around the testis in the
tunica vaginalis, forming a hydrocele. The hydrocele can be tapped to remove
the excess fluid by inserting a fine trocar and cannula through the scrotal skin.

Cryptorchidism
This refers to imperfect descent of the testis, which could be due to
abnormal androgen production. This results in inability to produce mature
spermatozoa as the temperature within the body retards spermatogenesis. The
descent may be incomplete, and the testis fails to reach the floor of the

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scrotum and may be found within the abdomen, within the inguinal canal at the
superficial inguinal ring, or high up in the scrotum. Maldescent, in which the
testis travels down an abnormal path, and may be found in the superficial fascia
of the ant. abd. wall above the inguinal ligament, in front of the pubis, in the
perineum or in the thigh.

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---------------------

Descent of the ovaries

The gubernacula (genital ligament), attached to the caudal ends of the
ovaries, aid in their descent, which is much less than that in males. The ovaries
are located just below the rim of the true pelvis.
- The cranial part of the gubernaculum, together with the ovarian artery and
vein, forms the suspensory ligament of the ovary, which suspends the
ovary from the pelvic wall
- The caudal part of the gubernaculum forms the ligament of ovary proper
and the round ligament of the uterus, which supports the ovary and
uterus in the pelvis.

-----------------------------------------------------------------------------------------------------------------
--------------------
Genital Ducts
2 pairs of indifferent genital ducts, the mesonephric/Wolffian and
paramesonephric/Mullerian ducts, are initially present in both males and females.
Their development is influenced by hormones.

Male Female
Mesonephric Testosterone, major Absence of testosterone causes
/ Wolffian androgen produced by regression of these ducts
ducts Leydig cells, causes
virilisation of these ducts
Paramesonep Mullerian-inhibiting Oestrogens (maternal,
hric / substance (MIS) / Anti- placental, foetal) and absence
Mullerian mullerian hormone (AMH) of MIS causes ducts to develop
ducts produced by Sertoli cells into uterine tubes, uterus,
causes regression of these and upper part of the vagina
ducts

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Male Genital Ducts
- Efferent ductules: Arise from
mesonephric excretory tubules.
Connect to rete testis.
- Mesonephric duct: Main genital
duct
o Elongate and become highly
convoluted near efferent
ductules to form epididymis
o Obtain thick muscular coat to form vas deferens from tail of
epididymis to seminal vesicles
o Forms the ejaculatory ducts beyond the seminal vesicles

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------------------
Female Genital Ducts
Paramesonephric duct: Formed from a
longitudinal invagination of epithelium on the
anterolateral surface of the urogenital ridge, this duct
forms the main female genital ductal system.
- Cranial vertical part: Opens into the abdominal
cavity with funnel-like structure with fimbriae.
- Horizontal part: Runs lateral to the mesonephric
duct then crosses ventrally in the
caudomedial direction. Establishes the broad
ligament of the uterus, dividing the pelvic
cavity into uterovesical pouches and Pouch of
Douglas
- Caudal vertical part: Comes into close contact
with opposite paramesonephric duct in the midline. The caudal tip projects
into the posterior wall of the urogenital sinus. Both parts are initially
separated by a septum, but later fuse to
form the uterus and cervix. The surrounding
mesenchyme forms myometrium; while the
peritoneal covering forms the perimetrium.

Vagina
The vagina is of dual origin:
- Sinovaginal bulbs: These are evaginations
from the pelvic part of the urogenital sinus
which proliferate to form a solid vaginal plate.
By the 5th month, it will be completely
canalized to from the lower part of the
vagina. The lumen is separated from the
urogenital sinus by the hymen.
- Vaginal fornices: These wing-like
expansions of the upper part of the
vagina form around the end of the uterus.
These are of paramesonephric origin.

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23
Agenesis of the Uterus
This is a rare condition where the uterus is absent as the result of a failure of the
paramesonephric ducts to develop.

Infantile Uterus
This is a condition in which the uterus is much smaller than normal and
resembles that present before puberty. Amenorrhea is present, but the vagina
and ovaries may be normal.

Failure of Fusion of the paramesonephric ducts

Failure of the paramesonephric ducts to fuse may cause a variety of
uterine defects:
- Uterus may be duplicated with 2 bodies and 2 cervices
- There may be a complete septum through the uterus, making 2
uterine cavities and 2 cervices
- There may be 2 separate uterine bodies with one cervix
- One paramesonephric duct may fail to develop, leaving one
uterine tube and half of the body
of the uterus.

----------------------------------------------

Indifferent External Genitalia

The indifferent external genitalia comprises of:
- Cloacal folds: Slightly elevated regions around
the cloacal membrane formed by migration of
mesenchymal cells from the primitive streak
(ectoderm) during the 3rd week of development.
o Cranial to cloacal membrane: Folds unite to
form genital tubercle (phallus)
o Caudal to cloacal membrane: Divided into
the urethral folds and anal folds when
the cloacal membrane is subdivided into
urogenital and anal membranes at the
6th week
- Genital swellings (Labioscrotal folds):
Pair of elevation on either side of urethral
folds.

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 Male Female
Developm Influenced by androgens Stimulated by oestrogens
ent
Genital - Initially located in inguinal Enlarge to form the labia
swellings region majora
- Move caudally and fuse, each
making up half the scrotum
- Halves separated by scrotal
septum
Genital - Rapidly elongates, pulling Elongates slightly to form the
tubercle urethral folds forward to form clitoris
urethral groove
Urogenita - Extends along the caudal Remains open to form
l groove aspect of the elongated vestibule
genital tubercle
- Lined by endodermal cells to
form a urethral plate
Urethral - Fuse over urethral plate to Do not fuse; Forms the labia
folds form penile urethra at end of minora
3rd month.
- The canal does not extend to
the tip of the phallus
- Ectodermal cells from the tip
of the glans penetrate inward
to form epithelial cord at the
4th month
- Canalizes to form the external
urethral meatus.

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