Placenta & Twinning

Introduction
When the blastocyst embeds itself in the maternal
endometrium it is covered with chorionic villi derived from
the syncitiotrophoblast and cytotrophoblast. The distribution
and size of the villi are not uniform throughout the surface of
the chorion.
The chorion frondosum consists of numerous villi over the
embryonic pole. This will contribute to the formation of the
placenta .
The chorion laeve contains very sparse villi over the
abembryonic pole. The villi will eventually disappear, and
here the chorionic membranes are formed.
The Placenta is derived from two sources:
The foetal chorion
The maternal deciduas
By the third week tertiary chorionic villi are formed.
















New chorionic villi continue to sprout out at different
gestational ages
At 9 -16 weeks they are termed mesenchymal villi
At 16 -25 weeks they are immature intermediate villi. At this
age the cytotrophoblast persist only in patches.
At 25-32 weeks they form mature intermediate villi.
After 32 weeks they sprout out terminal villi (consisting of a
thin syncitiotrophoblast and foetal capillaries with minimal
intervening mesoderm)

The Placenta consists of branched chorionic villi bathed in
lacunae of maternal blood. On the foetal surface of the
placenta the chorion forms a continuous surface from which
the villi arise. The cytotrophoblast proliferates from the tips
of the villi and forms a cytotrophoblastic shell on the
maternal surface of the placenta. Elsewhere the villi are lined
by syncitiotrophoblast, while the cytotrophoblast becomes
restricted to small patches.










The Decidua
The decidua is derived from the secretory endometrium,
which continues to proliferate and secrete under the
influence of persistent high levels of progesterone, which in
turn is stimulated by increasing levels of HCG, secreted by the
growing syncitiotrophoblast. As the decidual cells continue to
proliferate, they accumulate lipids and glycogen, and, the
whole decidua becomes more vascular.
Septa grow from the decidua and project into the intervillous
spaces dividing the placenta into 15 to 20 cotyledons.






At 4 weeks (2
nd
month) the amniotic cavity grows and
obliterates the chorionic cavity (extra-embryonic coelom).
The amnion fuses with the chorion to form the chorio-
amniotic plate.
The placenta at birth:
o Is 15 to 25 cm in diameter
o Consists of 15 to 20 cotyledons
o Weighs 500 to 600 grams
o Is supplied by 80 to 100 spiral arteries

Functions of the placenta

1. Exchange of gases mainly by diffusion
2. Exchange of metabolites:
a. Carbohydrates
b. Amino acids
c. Fatty acids
d. Vitamins
e. Electrolytes
Waste products: urea, creatinine, bilirubin etc

3. Transport of maternal substances:
a. Maternal antibodies IgG conveys passive
immunity to the new-born infant
b. Transferrin - for iron transport
c. Maternal hormones - may affect foetus
d. Chemical, drugs, viruses - all potentially
teratogenic
4. Secretion of hormones - into maternal circulation:
a. Human chorionic gonadotrophin
b. Progesterone and oestrogen
c. Somato-mammotropin
Passage of cells into the maternal circulation.
This is acquiring increasing importance
because new methods are being developed
to isolate the foetal cells from the maternal
blood, and use them for prenatal diagnosis
instead of the invasive methods of
amniocentesis and chorionic villus biopsy.


The umbilical cord consists of:
o Two umbilical arteries
o One umbilical vein
o Whartons jelly
o And, only its most proximal part,
o The yolk sac and vitello-intestinal duct
o The allantoic diverticulum
o A canal connecting the extra-and intra-embryonic
coeloms, which is subsequently obliterated.

The amniotic fluid
o 800 1000 ml
o functions as a shock absorber for the foetus
o Allows foetal movements
o Is replaced every 3 hours
o Circulates continuosly:
o It is ingested through mouth
o Excreted as urine

Abnormalities of amniotic fluid
1. Oligohydramnios
o Usually occurs with renal agenesis
o Causes foetal compression syndrome (Potters
syndrome)
2. Polyhydramnios
o Usually occurs with oesophageal atresia
Twinning
There are two types of twins:
a. Fraternal twins are the result of fertilization of two
oocytes. The two zygotes develop and implant
themselves separately. They have separate
placentae and amniotic cavities. Like all sibs born to
the same couple, they have half their genes in
common. They may be of different sex or of the
same sex.
b. Identical twins are derived from a single zygote,
which during early development divides into two
groups of cells that continue to develop
independently. Identical twins are always of the
same sex, and have identical genes. Identical twins
are in fact clones as the two individuals are derived
from the same cell.






Identical twins may share the
same placenta or amniotic
cavity, or they may have
different placentae and amniotic cavities, depending on the
developmental stage at which the separation of the
conceptus into
two twins occurs:

1. Separation of
the blastomeres

into two groups
which develop and implant separately. They result in
two separate placentae and gestational sacs (dichorionic,
diamniotic)


2. Separation of the inner cell mass or embryoblast into
two groups forms two amniotic cavities but one chorion
and placenta (form monochorionic, diamniotic twins)

3. Separation of the bilaminar disc into two groups of
pluripotent cells forms two embryos sharing a single amniotic
cavity, chorion and placenta (form monamniotic,
monochorionic twins)

4. Incomplete separation of the inner cell mass gives rise
to conjoined twins.

5. Anastomosis between the circulations of monoamniotic
twins may cause failure of normal growth and development
in one embryo










Development of the Heart and Cardiovascular System

The cardiovascular system begins to develop in the third week of gestation. Blood
islands (angiocysts) develop in the newly formed mesoderm, and consist of (a) a
central group of haemoblasts, the embryonic precursors of blood cells; (b) endothelial
cells.




Blood islands coalesce to form a vascular plexus. Preferential channels form arteries and veins .
Day 17 - Blood islands form first in the extra-embryonic mesoderm
Day 18 - Blood islands form next in the intra-embryonic mesoderm
Day 19 - Blood islands form in the cardiogenic mesoderm and coalesce to form a pair of endothelial heart tubes




The endothelial heart tubes fuse to form a single primitive heart tube with a cranial (arterial) end and a caudal (venous) end.

The heart tubes are derived from the cardiogenic mesoderm situated next to the pericardial
cavity, the cranial-most end of the intra-embryonic coelom.

Initially, at 18 days, the cardiogenic mesoderm lies at the most cranial end of the trilaminar
embryo.

After the formation of the head fold (at 20 days) the cardiogenic mesoderm is shifted ventrally
and comes to lie ventral to the primitive pharynx.

21 days.

The primitive heart tube is divided into a number of primitive
chambers separated by grooves.
The truncus arteriosus divides into a pair of aortic arches.
The sinus venosus consists of right and left horns


22 days.
The pharyngeal endoderm induces the cardiogenic mesoderm to differentiate into four
layers, surrounded by the pericardial cavity.




Development of a circulation
A circulation is established during the 4
th
week after the myocardium is differentiated. The cranial end communicates with the
paired branchial arches that open into paired dorsal aortae. These fuse into a single dorsal aorta. At this stage three main pairs of
arteries are present (i) to the head, (ii) vitelline arteries to the yolk sac and (iii) paired umbilical arteries to the placenta . Three
corresponding veins drain into the sinus venosus.





Folding of the heart tube
Folding of the heart tube occurs on days 23-28 at two sites: (i) the bulboventricular sulcus (bv), and (ii) the atrio-ventricular
groove (av). As a result the heart tube becomes S-shaped.







Cardiac Asymmetry
Folding occurs because of elongation of the heart tube, which causes it to become
asymmetrical.
As a result of folding of the heart tube:
1. The atrium lies dorsal to the ventricle, bulbus cordis and truncus arteriosus, and
bulges on either side of the truncus
2. The bulbus cordis lies to the right of the ventricle
3. The ventricular septum lies between the bulbus cordis and ventricle
4. The A-V opening overhangs both chambers

Formation of the transverse sinus of the pericardium

The heart is suspended in the pericardial cavity by a mesocardium, a double fold of coelomic
epithelium situated in the midline.
The mesocardium breaks down forming the transverse sinus of the pericardium. The heart
tube remains attached to the pericardium at its cranial (arterial) and caudal (venous)
ends. The transverse sinus lies dorsal to the heart tube between the arterial and venous ends,
and communicates the two sides of the pericardial cavity. It maintains the same relationship
in the adult heart.

Development of the Sinus venosus
Initially the veins entering the sinus venosus are
symmetrical. During the fourth week the venous system
becomes asymmetrical causing extensive remodelling of
the sinus venosus.
Initially three sets of paired veins enter the sinus venosus:
1. The common cardical veins enter the sinus venosus laterally. They receive:
a. the anterior cardinal veins from the cranial half of the body (head, neck and upper limbs)
b. the posterior cardinal veins from the caudal half of the body (abdomen and lower limbs)
2. The umbilical veins receiving oxygenated blood from the placenta
3. The vitelline veins drasining the gut and yolk sac.

These veins all pass through the septum transversum before entering the sinus venosus. At the same time the liver begins to
develop within the septum transversum from cells derived from the foregut. A venous plexus of sinusoids develops between the
liver cells and communicates with the umbilical and vitelline veins.
Venous symmetry is radically altered by:
1. establishment of left to right shunts in the venous system, and
2. obliteration of some veins draining into the sinus venosus

Three left to right shunts are formed:
1. A left to right shunt between the two anterior cardinal veins. This will form the left brachiocephalic vein.
On the left, the common cardinal, the posterior cardinal and most of the anterior cardinal veins are largely obliterated.
2. The ductus venosus - a preferential channel from the left umbilical to the right vitelline veins, bypassing the liver sinusoids.
The left umbilical vein loses its direct communication with the sinus venosus and the right umbilical vein is obliterated
3. The vitelline veins communicate by three anastomoses.






Consequences of rearrangement of the venous system
a) The cardinal veins
* The shunt between the two anterior cardinal veins forms the left brachiocephalic vein.
* On the left, the common cardinal, the posterior cardinal and most of the anterior cardinal
veins are largely obliterated. Their remnants form theoblique vein of the left atrium
* All the blood from the cardinal veins now drains into the right horn of the sinus venosus
b) The umbilical veins
* The left umbilical vein drains into the right horn of the sinus venosus via the ductus venosus,
and loses its direct communication with the sinus venosus
* The right umbilical vein is obliterated
c) The vitelline veins lose their direct communication with the sinus venosus. A preferential channel fromed of parts of the right
and left vitelline veins and the three anastomoses between them forms the portal vein, which drains into the hepatic sinusoids.
d) The right horn of the sinus venosus dilates considerably as it receives all the veins. It forms the sinus venarum part of the right
atrium. The left horn of the sinus venosus becomes small. It forms the coronary sinus.

Asymmetry of the sinus venosus shifts the sinu-atrial opening to the right of the common atrium.
Two flaps of endothelium project into the atrium from the sides of the SA opening forming transient right and left venous
valves. They unite near the roof of the atrium to form the septum spurium.

Development of the Heart and Cardiovascular System
II Septation of the Heart

Septation of the atrioventricular canal - Septum Intermedium.
26 days :
Superior and inferior endocardial cushions arise from the superior and inferior walls of the
atrio-ventricular canal. They are formed of sub-endothelial thickenings of cardiac jelly.
35 days: The AV cushions fuse separating right and left AV openings. The fused AV cushions
constitute the septum intermedium


Development of the atrioventricular valves
The mitral and tricuspid atrioventricular valves form between the 5
th
and 8
th
weeks. They valve cusps and their chordae tendinae
are formed by undermining of the ventricular myocardium.

Development of the Atrial Septum
Two atrial septa are formed, both of which contribute to the definitive atrial
septum. They are associated with two inter-atrial communications (ostia).

1. The septum primum begins to develop at 28 days. It is a thin, crescentic fold of
endocardium that arises craniodorsally and grows down to the AV cushions, leaving
anostium primum below its free edge. It fuses with the AV cushions at approx. 35
days, obliterating the ostium primum.

2. The ostium secundum is an opening in the upper part of the septum primum. It
forms at about 33 days i.e. before the ostium primum closes. It forms
by apoptosis(programmed cell death) as a number of small perforations that
coalesce.


3. The septum secundum begins to develop at about 33 days. It is a thick muscular septum that arises to the right of the septum
primum in the intersepto-valvular space (between the septum primum and the left venous valve of the SA opening). It grows
from the roof of the atrium but never reaches the AV cushion forming the fossa ovalis.


The final atrial septum is formed from both septum primum and septum secundum:

The final atrial septum is formed from both septum primum and septum secundum:



1. The muscular part of the atrial septum is derived from the septum secundum
fused with the septum primum
2. The ostium secundum is covered by the septum secundum
3. The limbus fossae ovalis is the free border of the septum secundum
4. The floor of the fossa ovalis is formed of septum primum - it is thin and membranous
and forms the flap valve mechanism











The Definitive Atria


The original sinu-atrial opening communicates entirely with the right atrium. The SA opening dilates greatly, and the right horn of
the sinus venosus is absorbed into the right atrium.

The definitive right atrium is formed from two parts:
a) the muscular part derived from the embryonic atrium - this part has musculi pectinati;
b) the smooth part derived from the sinus venosus (also called the sinus venarum part).
c) The smooth part of the right atrium receives three openings (I) the superior vena cava; (ii) the inferior vena cava and (iii)the
opening of the coronary sinus.
d) The crista terminalis, separating the smooth and muscular parts, and the valves of the inferior vena cava and coronary
sinus are derived from the right venous valve. They form one continuous curved line.


The definitive left atrium receives no contribution from the sinus venosus. Right and left pulmonary veins establish communication
with the left atrium. The left atrium also consists of two parts:
a) The smooth part is derived from the pulmonary veins that have been resorbed into the the left atrium till the level of their
division. Thus this part receives the openings of the four pulmonary veins.
b) The muscular part of the left atrium is derived from the left half of the embryonic atrium

Formation of the ventricular septum











Initially, the ventricle communicates with the atrium and the bulbus cordis communicates with the truncus arteriosus.
After folding of the heart at 28 days, the bulbus cordis and truncus arteriosus are situated to the right of the ventricle. The part of
the bulbus cordis that tapers to merge with the truncus arteriosus is the conus cordis. The conus cordis and truncus arteriosus
together form the outflow tract or cono-truncus.

The ventricle and the bulbus cordis merge into one big chamber. This has the AV openings
(inflow) to the left and the conotruncus (outlfow ) to the right. Two important rearrangement
that occurs at this stage are the realignment of the atrioventricular openings and the cono-
truncus to the middle of the common bulbo-ventricular cavity. This is essential for correct
septation of the ventricle.

The muscular ventricular septum grows from the bulbo-ventricular sulcus and is directed
dorsally and to the right towards the atrioventricular cushions but does not fuse with
them. Growth of the ventricular septum is arrested at the seventh week, leaving a
communication between the right and left ventricles. This gap is closed during the eighth
week by growth from endocardial tissue, which forms the membranous part of the ventricular
septum. The right ventricle is derived mainly from the bulbus cordis whereas the left ventricle is derived mainly from the embryonic
ventricle.


Septation of the cono-truncus
A pair of bulbar ridges (also called conotruncal ridges) arises from opposite sides of the cono-
truncus. They approach one another and fuse in the midline to form the spiral aortico-
pulmonary septum, separating the aorta and pulmonary trunk. The ridges are spirally oriented,
and the relative positions of the aorta and pulmonary trunk are also spirally arranged.

The development of the bulbar ridges begins at the lower end of the truncus arteriosus (level 3 in
Figure) and extends cranially into the truncus and caudally into the conus. The uppermost part of
the septum fuses with the dorsal wall of the truncus just beyond the origin of the 6
th
aortic arch.

The spiral extension of the bulbar ridges downwards into the conus forms the membranous part
of the the ventricular septum, together with a contribution from the AV cushions. This
downward extension continues the spiral and brings the aortico-pulmonary septum in line with
the ventricular septum.


Development of Aortic and pulmonary valves

These develop at the lower end of the truncus arteriosus. At this level there are four swellings of sub-
endocardial tissue - the right and left bulbar swellings and two acessory dorsal and ventral swellings.
Separation of the fused bulbar ridges forms the aortic and pulmonary vessels each containing three
swellings. Growth and excavation of the swellings results in the formation of the semilunar
valves. Formation of the semilunar valves is complete by the end of the 9
th
week.

Note the positions of the valves as in adult anatomy.
The aorta has one posterior valve and two anterior valves, above which the right and left coronary
arteries arise. The pulmonary trunk has one anterior and two posterior valves.


Development of the conducting system of the heart

Contraction of the heart by myogenic activity begins at about 28 days. The conducting system of the
heart (SA node, AV node, bundle of His and Purkinje fibres) consist of specialized cardiac muscle
cells. The SA node is thought to be derived from neural crest cells and is initially situated in the wall of
the sinus venous. The rest of the conduction system is thought to be derived from cardiogenic
mesoderm.