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
Once the ovum has been fertilized by the spermatozoon, a
zygote (single cell) is formed. This undergoes a rapid
succession of mitotic divisions (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
Trophoblast cells surrounding the embryonic cells
proliferate and invade deeper into the uterine lining.

Differentiation of the cell masses occur:

- Embryoblast (ICM) differentiates to form the epiblast
and hypoblast.
- Trophoblast cells (OCM) differentiates to form the
cytotrophoblast and syncytiotrophoblast.

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. Cephalocaudal flexion (in the
longitudinal direction) and lateral folding (in the
transversal folding) occur simultaneously, forming the
abdominal wall, permitting a delimitation of the embryo.
This also leads to enclosure of mesoderm and endoderm
by the ectoderm, which later forms the epidermis.

Neurulation, development of the CNS, also occurs.

Derivatives of the Germ layers

Ectoderm Mesoderm
Epidermis: Connective Tissue, Cartilage,
Hair, Nails, Sebaceous Glands Bones and Joints
CNS: Brain and Spinal Cord Walls of Heart
PNS Muscles:
Smooth, Striated and Cardiac
Sensory epithelium of sense Urogenital System: Kidneys,
organs Gonads and their Ducts,
Inner ear Suprarenal Cortex
Eye (lens) Mesothelium (Serous
membranes): Pleura,
Pituitary gland (hypophysis) Pericardium, Peritoneum
Teeth (enamel)
Epithelium of some organs Blood and Lymph cells
Endoderm
Epithelium of Digestive tube:
Foregut, Midgut, Hindgut
Parenchyma of Digestive tube:
Tonsil, Thyroid, Parathyroids,
Thymus, Liver, Pancreas
Epithelium of Respiratory
Tract:
Lungs
Middle Ear (Tympanic Cavity
and Eustachian tube)
Part of Bladder and Urethra

Fetal Period

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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)
- 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.

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Development of the Diaphragm

Germ Layer: Mesoderm formed in neck by fusion of myotomes of 3rd, 4th and 5th cervical segments.
Hence, the diaphragm’s 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.

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 180⁰
to come ventral to the esophagus and caudal to the developing
mouth.

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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 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 venosus Smooth part of right atrium (sinus venarum), coronary
sinus, oblique vein of left atrium
Primitive atrium Trabeculated parts of right and left atria
Primitive Trabeculated parts of right and left ventricles
ventricle
Bulbus cordis Smooth part of right ventricle (conus arteriosus),
smooth part of left ventricle (aortic vestibule)
Truncus Aorta, pulmonary trunk
arteriosus

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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 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 ⅔ 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 90⁰ counterclockwise
rotation. This occurs in the umbilical
cord which contains a space that is a
continuation of the primitive
peritoneal cavity.
4. Return to the abdominal cavity along
with a further 180⁰ 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.

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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)

Meckel’s 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.

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 4th week. Earlier groups of cells regress before more caudal groups are formed. By the end
of the 4th 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 5th week and becomes functional
at the end of the 1st 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 Bowman’s 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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 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

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 3rd 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.

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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.

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.

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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
5th week, invading the gonadal ridges in the 6th week.
If germ cells are absent, gonads do not develop.

The epithelium proliferates and penetrates the

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

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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 4th 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.

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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.

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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 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 of
abdominis 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.

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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
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.

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

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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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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.

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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
Development Influenced by androgens Stimulated by oestrogens
Genital - Initially located in inguinal region Enlarge to form the labia majora
swellings - Move caudally and fuse, each making
up half the scrotum
- Halves separated by scrotal septum
Genital - Rapidly elongates, pulling urethral Elongates slightly to form the clitoris
tubercle folds forward to form urethral groove
Urogenital - Extends along the caudal aspect of Remains open to form vestibule
groove the elongated genital tubercle
- Lined by endodermal cells to form a
urethral plate
Urethral folds - Fuse over urethral plate to form Do not fuse; Forms the labia minora
penile urethra at end of 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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