Systemic Embryology

Prof. Hany Shawky Nadim

Systemic Embryology

1

DEVELOPMENT OF THE LIMBS nd

Before the 2 month, the embryo has no limbs. They nd develop totally during the 2 month (i.e., 5-8 wks). th

5 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 . th 6 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 proximodistal order. th 7 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 t he LL.

-

A muscle mass develop inside the bud around the bones.

th

8 week

-

The digits become free

The limb buds undergo adduction and rotation: Upper limb buds Rotates 90° laterally. -The preaxial digit Results:  Digits: (thumb) becomes lateral. -The flexors become ant.  Muscles: & the extensors post. -The preaxial border  Bones: (radial) becomes lateral.

Lower limb buds 90° medially. - The preaxial digit (big toe) becomes medial. -The flexors become post. & the extensors ant. -The preaxial border (tibial) becomes medial

rd

3 month: Nails appear th 4 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].


-

Systemic Embryology

2

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) i s 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 3 The C.V.S. is totally mesodermal in origin.

rd.

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 intraembryonic 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.

week.


3

-

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 p ericardial sac.

-

The endocardial heart tube invades the pericardial sac from its dorsal aspect dividing it into a visceral layer and a parietal layer. la yer.

-

Five chambers appear as dilatations (separated by constrictions) in the heart tube. In a caudo-cranial order, they are: sinus 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.

Systemic Embryology

FATE OF THE SINUS VENOSUS

-

Initially, the sinus venosus opens into the middle of the back of the primiti ve 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 valves . 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 incorporated into the right atrium due to widening of the sino-atrial orifice giving the smooth posterior part of t he 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 of SVC  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.


4

Systemic Embryology

SEPTATION OF ATRIA  In the A-V canal between the atrium and ventricle, two endocardial cushions, cushions, ventral and dorsal project from the walls and fuse together forming the septum 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 corresponding atrium while the lower parts form the mitral and tricuspid t ricuspid orifices. Local endothelial endothelial proliferations proliferations form the cusps 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 l eft 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 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 finall y closed. Just before complete closure of the foramen primum, the upper part of the septum primum ruptures forming another opening, the foramen 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 ovale . septum secundum is called the foramen 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 ovalis . The septum primum in the site of the foramen ovale forms the fossa the fossa ovalis. 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 1. right half of the primitive atrium 2. absorbed right horn of sinus venosus 3. upper part of the right A-V canal

left atrium 1. left half of the primitive atrium 2. absorbed pulmonary veins 3. upper part of the left A-V canal


5

THE REMAINING CHAMBERS 

 

The lower part of the bulbus cordis, together with the common ventricle form one chamber which has trabeculated wall. wall. It forms form s 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, foramen. It is derived from the which is called the interventricular foramen. 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 repositioned to become 1 ant. + 2 post in i n the aortic orifice and 1 ant. + 2 post. in the pulmonary orifice.



One septum in the truncus arteriosus: Spiral aortico-pulmonary 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 inflowing Right / 2 of the bulbopart ventricular chamber 1 outflowing Ventral / 2 of the proximal part part of bulbus cordis 1

left ventricle Left / 2 of the bulboventricular chamber 1 Dorsal / 2 of the proximal part of bulbus cordis 1

The myocardium of each ventricle shows spongework cavitation resulting in the formation of the trabeculae carnae , papillary muscles and chordae tendinae .

Systemic Embryology


6

Systemic Embryology

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 S yndromes. b. Environmental causes: e.g., German measles virus. vir us. 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 t he 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 co ngenital 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).


Systemic Embryology

7

DEVELOPMENT OF ARTERIES 

At first, there are 6 aortic arches on each side of the neck (each runs in the corresponding pharyngeal 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 f ollowing

arch rd 3 th

4 th 6

Right Left The common carotid a. & internal carotid a. (the external carotid arises as an outgrowth). Part of the right subclavian a. Part of the arch of aorta 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. th.

b. 4

left aortic arch. th

c. Part of the left dorsal aorta till the 7 intersegmental artery. 2. The innominate artery is derived from the right horn of the aortic sac . 3. The subclavian arteries: th

a. The right: is derived from the right 4 aortic arch + part of the right dorsal th aorta + the right 7 intersegmental intersegmental artery. th

b. The left: is derived from the left 7 intersegmental artery. 4. The descending aorta is derived from the part of the left l eft dorsal aorta caudal to th the left 7 intersegmental intersegmental branch + the th e single distal aorta. th

N.B: The recurrent laryngeal nerve is the nerve of the 6 pharyngeal pharyngeal arch. It is pulled th down by the 6 aortic arch forming a loop before it returns r eturns to the neck.  

On the left side , it hooks around the ductus arteriosus in the thorax . th th On the right side , the distal part of the right 6 aortic arch + the right 5 aortic arch disappear; the nerve hooks around the right subclavian artery in the neck (i.e., th the derivative of the right 4 arch).

B- Fate of the Branches of the Dorsal Aortae: I. The intersegmental (somatic) branches: branches: pass laterally between somites: st

-

th

Cervical: 1 – 6 : are connected by longitudinal anastomotic channels which form th the vertebral artery and other arteries. The 7  subclavian a. st

-

th

Thoracic: 1 - 11 st

th

Lumbar: 1 - 4





intercostal arteries & 12

lumbar arteries & 5

th



th



subcostal a.

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 suprarenal arteries. 3. Renal arteries. 4. Gonadal arteries.


8

Systemic Embryology

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 i s 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 2 preductal coarctation of aorta

ry.

to

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 i s 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 ili ac 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: - IVC: double IVC or absent IVC


9

Systemic Embryology

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 placenta along the left umbilical vein to the left branch of portal vein. 2. Then reaches the 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. i s high (e.g., during uterine contraction) to prevent overloading of the heart. 3. In the IVC, oxygenated oxygenated blood mixes with little deoxygenated deoxygenated blood returning from lower extremities & abdomen; this atrium , where: highly oxygenated blood reaches the right the right atrium, a. Most of it passes to the left atrium via the foramen foramen ovale as pressure in the left atrium is lower l ower than the right. b. Little amount passes to the right 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 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 unoxygenated from the ductus arteriosus) passes in the descending aorta where it: a. Supplies the abdomen abdomen and lower lower limbs. b. Passes in the common iliac arteries 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 t emperature so, blood returns from the functioning lungs to the left atrium. cord is ligated, so, no blood returns via the b. The umbilical cord is 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.


10

Systemic Embryology

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. laryngo-tracheal tube. b. Ventral part called laryngo-tracheal



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 inlet. The inlet is obliterated pharynx. This opening is called the laryngeal inlet. th th transiently between the 8 and 10 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 6 th 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 o rders of division).

B- The surrounding surrounding splanchnic splanchnic mesoderm mesoderm forms cartilaginous plates, smooth muscles, connective tissue & blood capillaries. C- Invasion of the pleura: each lung grows laterally around the foregut for egut and invaginates the part of the intraembryonic coelom, (i.e., the pericardio peritoneal 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: th. 1. Pseudoglandular period (up till the 4 month): only terminal bronchioles are formed. Histologically, the lung resembles an exocrine gland. Elements


11

Systemic Embryology

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. th 3. Terminal sac period (6 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. th Surfactant production reaches adequate levels by the 7 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, th e alveolocapillary membrane is thin enough to permit p ermit sufficient gaseous exchange. Breath Movements: birth , they can be detected by ultrasonography. As the lung is not a  Before birth, respiratory organ before birth, these prenatal breath movements cause: 1. Suction of amniotic fluid into the airway. 2. Training of the respiratory respiratory muscles.  At birth, birth, the fluid in the airways (amniotic fluid + bronchial secretions) becomes becomes replaced by air via 2 mechanisms: mechanisms: 1. Some become expelled expelled by pressure on the thorax during labour. 2. The majority is absorbed by pulmonary pulmonary capillaries & more importantly importantly by pulmonary lymphatics.  Medicolegally, the lungs of a baby who was born alive & died after birth contain air, thus can stil l born baby sink. float on water. On the other hand, the lungs of a still Anomalies:

(1) Esophageal 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. polyhydramnios. (2) Surfactant deficiency = hyaline membrane 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 of the gut tube which is formed of 3 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. yolk sac by the vitello-intestinal duct. 3. Mid-gut in between. Connected to the yolk sac  The cranial end of the 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






12

Systemic Embryology

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 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 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 t ransverse 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 of the uro-genital system.  

The mucosa is derived from the endoderm of the 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 of the esophagus. The liver develops within the ventral mesogastrium. The part of the of the mesogastrium




13

Systemic Embryology

between the stomach and liver forms the lesser omentum. The enlarging liver pushes the cardiac end to the left of the 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 of lesser sac between its anterior 2 layers and its posterior 2 layers. Later, adhesions occur, obliterating most of the 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 of the muscle of the of the pylorus  obstruction & vomiting. 2. Thoracic stomach & hiatus hernia: the whole stomach or part of it of it lies in the thorax, due to short esophagus. 3. Reversed rotation as a part of situs of situs inversus totalis. 4. Hour-glass stomach: constricted middle part.

SPLEEN left layer of the mesogastrium.  Develops from the mesodermal cells of the 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 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 of the mid-gut. Just above the liver bud arises from the convexity of the duodenal junction of both of both parts, a liver bud loop. The whole loop is connected to the posterior abdominal wall by a st mesoduodenum. Also, the 1 inch is connected to the ventral mesogastrium. mesogastrium.  The duodenal loop rotates loop rotates,, with the stomach, 90º to the right until it rests on the peritoneum of the of the posterior abdominal wall and fuses with it. The fused peritoneal surfaces become absorbed, thus the duodenum becomes retrobecomes retrost peritoneal except peritoneal except the 1 inch.  The opening of the of the liver bud (the future opening of the of the common bile duct) is shifted is shifted to to the posteromedial aspect of the duodenal loop due to unequal growth of its of its walls.  The lumen becomes obliterated , by proliferation of its of its epithelial th rd lining, in the 6 week. Recanalization occurs in the 3 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.


14

Systemic Embryology

LIVER & BILIARY SYSTEM  A solid liver of the duodenal loop at the solid liver bud arises from the convexity of the end of the fore-gut . Later it becomes canalized.  The bud grows between the 2 layers of the 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 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 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. th  Bile formation starts in 12 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 triangular ligaments (Rt. & Lt.): between liver & diaphragm. 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; 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 retroperitoneal.  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 . rd  Acini arise as buds that remain connected to the ducts while islets of Langerhans arise, in the 3 th month, also as buds that disconnect from the ducts & secrete insulin in 5 month.

ANOMALIES: 1. Annular pancreas: pancreas: a ring of pancreatic tissue encircling encircling the duodenum. 2. Absence of ventral pancreatic duct: the sole dorsal pancreatic duct opens above the C.B.D. 3. Accessory pancreatic pancreatic tissue in the stomach or intestine.




15

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: st 1. Herniation & 1 rotation th  Occurs during the 6 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. 

nd

2. Reduction & 2 rotation: th  Occurs during the 10 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 arter y. st  The 1 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: nd 1. The transverse colon crosses infront of the 2 part of duodenum. rd 2. The sup. mesenteric a. crosses infront of the 3 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. th 6. The vitellointestinal duct becomes absorbed in the 6 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 t he ileocecal junction in 2% of people.  Fecal fistula: connecting the ileum with the umbilicus.  Vitelline cyst = persistent middle part of the duct.

Systemic Embryology


16

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); segment); above this the t he colon is greatly distended.

Systemic Embryology


Systemic Embryology

17

DEVELOPMENT OF THE URINARY SYSTEM THE KIDNEY

Three sets of kidneys appear successively in the intermediate cell mass mesoderm ;

Time Site

PRONEPHROS th Beginning of 4 wk cervical region

Structure

 

Function Fate

7 tubules without glomeruli + 1 collecting duct opening in the cloaca

not functioning in humans th by the end of 4 wk, the tubules disappear & the duct becomes mesonephric duct

MESONEPHROS th End of 4 wk thoracic & upper lumbar regions

METANEPHROS th In 5 wk lower lumbar and sacral regions

70 tubules with glomeruli join the mesonephric duct

Ureteric bud (collecting ducts) +  metanephric cap (1-3 million tubules with glomeruli) nd Functions during 2 ½ of pregnancy Persists as the permanent kidney

Functions transiently It is transformed to:  Genital duct in ♂  Vestigial 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 form renal vesicles, 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 milli on nephrons are developed per kidney .


18

Systemic Embryology

III. Further changes occur to the developing kidney: Shape; is lobulated at birth then becomes smooth. 1. Position; is initially in the pelvis, later ascends to the abdomen. This is caused by growth of 2. the body caudal to the kidneys which progressively occupy higher levels. Blood supply; initially, from the median sacral artery then, from the common 3. iliac artery, then from the aorta. Rotation; At first, its hilum looks forwards then it looks 4. 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 i s 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 solitar y kidney. 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). 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. Pelvic Kidney: Caused by failure of one kidney to ascend through the arterial fork formed by the umbilical arteries. 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 . Persistent Fetal Lobulation. Aberrant Renal Artery(s): enters the kidney through one of its poles (usually the lower pole) and not through its hilum.

2.

3.

4. 5.

6. 7.

THE URINARY PASSAGES “Ureter - Urinary bladder – Urethra” – 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 t he 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


Systemic Embryology

19

umbili cus and umbilical mesonephric ducts and the allantois (a process which extends to the umbilicus cord). It differentiates into 3 parts: Fate in male 1. the urinary bladder (except Vesicothe trigone) urethral part 2. prostatic urethra above the ejaculatory ducts 1. prostatic urethra below the Pelvic part ejaculatory ducts 2. membranous urethra penile urethra except the part in Phallic part the glans which is ectodermal   

Fate in female 1. the urinary bladder (except the trigone) 2. the whole urethra

Both form the vestibule of vulva, from which the lower 2/3 of the vagina arises as bud

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: Urachal fistula: fistula: urine drains from the umbilicus. a. Urachal sinus: sinus: patent proximal or distal part of the urachus. b. Urachal cyst: cyst : cystic dilation along the course of the urachus. c. 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 r each the ridges, the gonads do not develop. Hence, the primordial germ cells have an inductive influence on its development.


20

Systemic Embryology

2. The genital ridges: th

-

Appear in 6 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 7 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.

th

TESTIS:

-

-

If the embryo is a male the t he primordial germ cells carry XY sex chromosomes. A gene on the Y chromosome, called the testis-determining 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 i nto 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: Spermatogonia. 1. Primordial germ cells (endodermal)  Spermatogonia. 2. Supporting cells (mesodermal) Sertoli cells. 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 M IF suppresses development of the paramesonephric 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 t he genital (scrotal) swelling. The gubernaculum guides the testis during its descent.

-

The testis descends in two stages: o Internal descent: rd  The testis reaches the deep inguinal ring in the 3 month.  Cause: relative elongation of the posterior abdominal wall in an upward direction, without corresponding elongation of the gubernaculum. gubernaculum. Thus, it is a growth displacement rather than active migration. o External descent (through the inguinal canal): th th  It starts in the 7 month & reaches the scrotum in the 8 month.  Causes : Shortening of the gubernaculum due to atrophy of its


Systemic Embryology

21

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: Undescended Testis (cryptorchidism ): 1.

-

Occurs in 3% of all full-term full-t erm 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 Undescended testis should be treated surgically because it has increased risk to develop malignant tumors.

-

Sites of undescended 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.

-

Maldescended Testis:

2.

-

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. gubernaculum. Maldescended Maldescended testis should be treated t reated surgically & placed in the scrotum because it is liable to injury in this unprotected position.

Absent testis (Agenesis) or Double testis: unilateral or bilateral. Hydrocele: collection of peritoneal fluid in the processus vaginalis that remains connected to the peritoneal cavity by a narrow channel. Congenital lnguinl Hernia: herniation of abdominal contents into a patent processus vaginalis when its neck is wide enough. Polycystic Testis:

3. 4. 5. 6.

-

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,


22

Systemic Embryology

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 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 epididymis . 1. vasa efferentia & head of epididymis. 2. Some embryonic remnants = superior aberrant ductule + inferior aberrant ductule + paradidymis . mesonephric duct: give epididymis , vas deferens , seminal vesicle & ejaculatory duct 1. body and tail of epididymis, bud & trigone of urinary bladder. 2. ureteric bud & 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 bud and trigone 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


23

Systemic Embryology

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 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, t estosterone, while the paramesonephric 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 f ornices). The myometrium is derived from the t he 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 h ypoplasia it is 1:2). (4) Failure of canalization: 1. Atresia of the cervix or the vagina .


24

2. Imperforate hymen: passes unnoticed till puberty, puberty, when retention of vagina  a painful swelling (hematocolpos)

Systemic Embryology

menstrual blood in the


25

EXTERNAL GENITALIA I. Indifferent Stage: 5 elevations el evations 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: Hypospadias: 1.

-

-

2.

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). Epispadias:

-

3. 4.

The urethral meatus is found on the under aspect of the penis.

The urethral meatus is found on the dorsum of the penis .

It is usually associated with ectopia vesica. Divided or bifid penis: the two sides of the genital tubercle do not fuse. Agenesis of penis or Micropenis.

Systemic Embryology


Systemic Embryology

26

ACCESSORY GLANDS: Two sets of buds arise from the urogenital sinus in both sexes: Derivative in males Cranial buds (from prostatic glands pelvic part) Caudal buds (from bulbo-urethral glands phallic part) (of Cowper)

Derivative in females urethral glands (of Littre) great vestibular glands (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 Pseudohermaphrodite : e.g. testicular feminization syndrome

-

Patient has 44+ XY chromosomes but the t he 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 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 l abia majora resembling a scrotum.


Systemic Embryology

27 SUMMARY

Structure Mesonephros:Mesonephros:- Tubules: - Duct:

Urogenital sinus: Vesico-urethral part: Pelvic part: Phallic part: Glandular buds: buds: Cranial (from pelvic part) Caudal (from phallic part) Indifferent gonad: Coelomic epithelium: 1ry (medullary) cords: 2ry (cortical) cords: Endodermal germ cells: Mesodermal cord cells: Tunica albuginea: Mesoderm: Gubernaculum: Processus vaginalis: Descent of gonad: Communication with ducts Genital Duct: Paramesonephric duct: Mesonephric duct: External Genitalia: Genital tubercle (phallus): Genial (urethral) folds: Genital (labioscroal) swellings:

Fate in males Fate in females Epididymis + remnants Epoophoron & paroophoron Duct of epididymis + vas deferens + Gartner’s duct seminal vesicle + ejaculatory duct. Trigone & ureteric bud. Trigone + ureteric bud + back of prostatic urethra above seminal colliculus Urinary bladder (except trigone) trigone) + upper ½ of prostatic urethra Lower ½ of prostatic urethra + membranous urethra Penile urethra (urethral plate) except part in glans

Urinary bladder bladder (except trigone) trigone) + whole urethra Vestibule + the lower 2/3 of vagina) Vestibule

Prostatic glands Bulbo-urethral (Cowper) gld Testis Mesothelium Persist Not formed Spermatogonia Sertoli cells Thick Cells of Leyding Disappears Tunica vaginalis + vestige Internal & external occurs

Urethral glands (of Littre) Great vestibular (Bartholin) Ovary Germinal epithelium Degenerate  medulla Persist Oogonia  1ry oocytes Follicular cells Thin Stroma & theca cells Lig. of ovary & of uterus Disappears Internal none

Appendix testis + prostatic utricle (!) See above

Fallopian tubes + uterus + vaginal fornices See above

Dorsum of penis + glans Fuse raphe under penis Fuse scrotum (with septum)

Clitoris Separated Labia minors Separated Labia majora

Systemic Embryology

Recommend Documents