INTRODUCTION TO HUMAN EMBRYOLOGY

A.HENRY SATHANANTHAN
Monash Institute of Reprou!tion " De#e$op%ent& Monash Uni#ersit'&
Me$(ourne
henr'.sathananthan)%e.%onash.eu.au

OB*ECTI+ES O, THIS CHA-TER
To introu!e 'ou to./

1. The first 8 weeks of human development the embryonic period.

2. The processes of fertilization, cleavage, germ layer formation and primary
organogenesis.

. !ome clinical aspects of these processes.

". #hysiology of the embryo placentation.

$. %ritical periods of development and some congenital malformations.

&. 'asic te(ts, atlases, slides and %)*+,-s, since embryology is a visual
sub.ect.

INTRODUCTION
/mbryology deals with the study of the human embryo during the first 8 weeks of
development. 0t is important to know the events that occur in the beginnings of life,
when all the blueprints of the human body are laid down in the embryo. The
embryonic period is followed by the foetal period 1months *23 when there is
e(tensive growth and differentiation and when the embryo ac4uires a more human
form 1see separate chapter3. )evelopment is a long comple( process which
transforms a single cell 1fertilized ovum3 into a comple( multicellular organism.
The development of the embryo and foetus is the prenatal period of development.
0A ti%eta($e of prenata$ e#e$op%ent is i$$ustrate in Moore& 12324
)evelopment is a comple( process which transforms a single cell into a comple(
multicellular organism.

EMBRYONIC -ERIOD
/mbryonic development begins at fertilization 1day 13 followed by cleavage of the
embryo and its
implantation in the uterus 1week 13. This is followed by the differentiation of the
primary germ layers 1week 3 and culminates in primary organogenesis when the
tissues and ma.or organ rudiments of the embryonic body are formed 1weeks "*83.
The embryonic period may be temporally considered in " phases5*
First Week: 6ertilization, cleavage and onset of implantation 1pre*implantation
phase3.
Second Week: 6ormation of bilaminar embryo, deep implantation and
establishment of uteroplacental circulation.
Third Week: 6ormation of trilaminar embryo 1gastrulation3, somites, chorionic
villi and neurulation.
Fourth to Eighth Weeks: 6ormation of the embryonic body, primary
organogenesis and placentation.
The physiology of the embryo 1foetal membranes and placenta3 and some
congenital malformations during critical periods of development will also be dealt
with in this chapter.

THE ,IRST 5EE6. Ga%etes& ,erti$i7ation& C$ea#a8e an I%p$antation
The pre*implantation phase of development begins with fertilization and
culminates in the implantation of the blastocyst in the uterine endometrium. ,ur
knowledge of the first week of development has advanced immensely in the past
27 years, since the advent of in vitro fertilization 10863 and assisted reproductive
technologies 19+T3. 0See our at$as of Ear$' Hu%an De#e$op%ent for ART 9
Sathananthan et a$ 122:;122< for i$$ustrations.4
a) Gamete structure: sperm and egg
'riefly, the spermatozoon is a highly specialized torpedo*shaped cell 1: 7m
long3 for motility and, of course, for fertilization. 0t is composed of a head,
midpiece 1body3 and a tail 1flagellum3. The head carries the nucleus with the
paternal chromosomes and is capped by a modified lysosome 1acrosome3 covered
by the cell membrane. The midpiece consists of the base of the a(oneme
originating from the sperm*neck, where is located the functional paternal centriole
hidden in a ;black bo(<. The midpiece has a spiral of mitochondria around the
a(oneme which provides 9T# for sperm motility and nine dense fibres surrounding
the a(oneme. The a(oneme consists of 2 peripheral doublets and a central doublet
of microtubules 12=2 organization3 that e(tends into the tail, characteristic of cilia
and flagella and is the motile component of the cell. The tail has a ring of > dense
fibres and a fibrous sheath around the a(oneme.

The spermatozoon is a highly specialized cell for motility and fertilization.

The mature egg or oocyte is a large unspecialized cell 1:127m in diameter3
compared to the spermatozoon. 0t has no nucleus but has a maturation spindle
arrested at metaphase 00 of meiosis. The spindle is barrel*shaped and aligned at
right angles to the oocyte surface, where the first polar body is located within the
#8!. The egg vestments consist of a gelatinous zona pellucida 1shell3 surrounded
by several layers of follicle cells that make up the cumulus oophorus. The cumulus
is e(panded and gelatinous in mature oocytes. The egg cell has most of the
components of somatic cells but lacks rough endoplasmic reticulism. 0t has cortical
granules beneath the cell membrane, which play a role in fertilization.
0See our at$ases Sathananthan et a$& 122:; 122< pu($ishe (' the epart%ent
for etai$s of 8a%ete stru!ture an fun!tion& an CD/ROM& Sathananthan "
E=ars& 122>4
The oocyte is a large unspecialized cell compared to the spermatozoon
b) Gamete transport
-ature sperm 1several millions3 are e.aculated into the vagina after intercourse,
enter the uterus through the cervi( and swim up to the far end of the oviduct
1ampulla3 in about $ minutes, where fertilization occurs. ,f the millions e.aculated,
only a few hundred reach the ampulla. These are the most motile in the e.aculate.
!perm capacitation 1a physiological process3 occurs somewhere in the reproductive
tract, where sperm ac4uire the ability to penetrate the vestments of the oocyte. 0n
vitro, it takes place during the sperm preparation procedure 1washing and layering3
for 9+T. ,nce at the surface of the egg, it has to penetrate the cumulus oophorus
1follicle cells around the egg3 and the gelatinous shell 1zona pellucida3 before
gamete fusion occurs. #enetration is aided by sperm motility and the acrosome
reaction 19+3, which is the morphological e(pression of capacitation. )uring the
9+ the surface membranes of the acrosome vesiculate releasing 2 important
enzymes hyaluronidase and acrosin 1protease3, which enable sperm to penetrate
the cumulus and zona, respectively, and reach the perivitelline space 1#8!3
surrounding the egg.

!perm penetration is aided by sperm motility and the acrosome reaction

The mature egg 1oocyte3 is ovulated around day 1" of the natural menstrual cycle
0See Moore& ?1232@; Larsen& ?1223@4, released from the ovary into the peritoneal
cavity and immediately sucked up through the infundibulum of the 6allopian tube
1oviduct3 by its ciliary action into the ampulla. ?ere fertilization occurs and
development begins. ,ocytes remain viable for up to 12 hours after ovulation,
while sperm can survive up to 2" hours in vivo. !perm, however can be kept alive
in vitro up to 2* days and still retain their fertilizing capacity, while eggs too can
survive for about 27*2" hours, in vitro.
6ertilization occurs in the ampulla of the oviduct soon after ovulation

c) Fertilization
This involves the spontaneous fusion of two germ cells sperm and egg to form
a zygote. The zygote or fertilized egg is the first cell of the new baby. 6ertilization
essentially restores the diploid number 12n @ "&3 of chromosomes of somatic
1body3 cells bringing the fatherAs and motherAs genomes together.
The mature sperm cell is formed in the testis 1male gonad3 by a process of meiotic
maturation called spermatogenesis, while the mature oocyte is formed likewise in
the ovary 1female gonad3 during oogenesis. /ach gamete has a haploid number of
chromosomes 1n @ 23, having undergone meiosis 1reduction division3 during
gametogenesis 1formation of gametes3. The zygote has the diploid number of
chromosomes 12n @ "&3. 'iparental inheritance of chromosomes leads to species
variation, since there is independent assortment of paternal and maternal
chromosomes among the germ cells during meiosis. !e( is also determined at
fertilization.

6ertilization involves the spontaneous fusion of two germ cells sperm and egg
to form a zygote

d) Mechanics of fertilization
The ma.or events that take place simultaneously or soon after fertilization are
summarized as follows5
1i3 !perm oocyte fusion5 the midsegment of the sperm membrane
fuses with that of the egg followed by sperm incorporation into the
egg to form a male pronucleus 1-#B3.
1ii3 !oon after gamete fusion there is a sperm*induced calcium wave in
human oocytes.
1iii3 The egg completes its second maturation division, abstricting the
second polar body and a female pronucleus 16#B3 is formed within
the ooplasm. The egg has now completed meiosis and the 6#B is
haploid.
1iv3 !perm fusion triggers the cortical reaction which involves the
e(ocytosis or release of cortical granules into the #8!.
1v3 %ontents of released cortical granules interact with the zona zona
reaction * which chemically hardens the zona to prevent polyspermy.
,nly one sperm needs to fertilize the egg.
1vi3 9 sperm aster is formed and the male and female pronuclei migrate
to the centre of the egg, where they associate but do not fuse. 9part
from the fatherAs chromosomes, the sperm introduces the centriole,
which is the active division centre within the embryo during mitosis
1cleavage3.
Thus fertilization is a comple( process, which essentially involves activation of the
egg to develop further into an embryo and foetus.
0,or ia8ra%s an i$$ustrations see at$ases& Sathnanthan et a$& ?122:; 122<@4

6ertilization is a comple( process, which essentially involves activation of the egg
to develop further into an embryo and foetus.

CLEA+AGE. RE-EATED MITOSES ?CELL DI+ISION@
!oon after fertilization, the activated egg 1ovum3 cleaves as it travels down the
oviduct to enter the
uterus. %leavage involves repeated mitotic divisions with little or no growth. The
ovum or zygote divides into 2, ", 8, 1&, 2 cells and becomes a morula and
blastocyst, when divisions become irregular. The functional sperm centriole
1centrosome3 introduced at fertilization replicates and first forms a sperm aster,
which then splits to form a bipolar spindle about 27 hours after fertilization. The
male and female pronuclei, formed :12 hours after fertilization, dissociate their
envelopes and the paternal and maternal chromosomes come together and organize
themselves on this spindle, a stage called ;syngamy<. This establishes the
embryonic genome, which is activated later on between the "*8 cell stage in the
human. The first cell division occurs around 2" hours after fertilization and a 2*cell
embryo is formed. The embryo then divides into ", 8, 1&, 2 cells called
blastomeres and forms a morula 1mulberry3, which develops a fluid filled cavity to
become a blastocyst. 9fter the 8*cell stage, the embryo becomes compact
1compaction3 when cells increase contact with one another and develop an inside*
outside polarity, which later gives rise to a mass of cells within the blastocyst * the
inner cell mass that becomes the embryo proper 1embryoblast3 and an outer layer
of cells which forms an epithelium and gives rise to placental membranes
1trophoblast3.This is the first sign of cell differentiation 1cells becoming different3
in the human embryo. The morula enters the uterus on day *" of development.

%leavage involves repeated mitotic divisions with little or no growth

BLASTOCYST HATCHING AND SU-ER,ICIAL IM-LANTATION ?DAY
<@
The blastocyst e(pands as hydrostatic pressure of fluid increases within its cavity
and it hatches out of the zona 1day $3 through a hole believed to be digested by
enzymes, and s4ueezes its way out. 0t now closely adheres to the uterine
endometrium and trophoblast cells proliferate and form a syncytiotrophoblast
1common cytoplasm with several nuclei3 which invades the uterine epithelium.
The endometrial stroma responds by becoming secretory 1decidual reaction3,
while uterine glands enlarge and the uterus becomes vascularized and edematous,
due to the influence of progesterone and oestrogen secreted by the corpus luteum
of the ovary. 9fter implantation the trophoblast produces human chorionic
gonadotrophin 1h%C3 which can be detected in the motherAs urine during the first 2
months of pregnancy 1pregnancy test3. Dater the placenta secretes progesterone, as
well. 0f there is no pregnancy the corpus luteum degenerates after about 1 days.
The normal site of implantation is the endometrial lining around the cavity of the
uterus 1body of the uterus3. /ctopic pregnancies result when the embryo implants
outside this region, e.g., in the tube or cervi( this will be dealt with in another
chapter.
E,or ia8ra%s of !$ea#a8e/sta8e e%(r'os see at$as/ Sathananthan et a$ ?122:@;
Moore ?1232@; Lan8%an ?123A@4

9fter implantation the trophoblast produces human chorionic gonadotrophin 1h%C3
which can be detected in the motherAs urine

CLINICAL A--LICATIONS. TREATMENT O, IN,ERTILITY
The greatest advances in assisted reproduction stem from the recent development
of 086 and 9+T technologies which has led to a better understanding of human
development in the first week. This was a grey area before the advent of these
techni4ues. %onse4uently, we have now an indepth understanding of the events of
fertilization, cleavage and abnormalities, thereof. 9part from 086, the single
techni4ue that has revolutionized the treatment of infertility is intracytoplasmic
sperm in.ection 10%!03. This successful techni4ue of assisted fertilization violates
most of the norms of fertilization since the sperm is in.ected directly into the
oocyte, bypassing its vestments and pre*empting natural sperm*egg fusion. Fe
have to wait and see the long term effects of this technology. This will be dealt
with at length in another chapter on subfertility.
9nother e(citing finding is the paternal inheritance of the centrosome, which
regulates early cleavage in the human embryo 0see at$as& Sathananthan et a$&
122<4 which led us to postulate a new theory of infertility which states that a bad
sperm with poor motility may result in a poor 4uality embryo, especially after
0%!0. This hypothesis is now gaining wide acceptance both in the human and larger
mammals. The male has to share e4ual blame for the causes of infertility.

Fe have now a better understanding of hormonal interactions and monitoring in
the stimulated cycleG embryo development in vitro including co*culture methodsG
chromosomal aberrations in gametes and embryosG uterine receptivity to
implantation and, of course, the techni4ues that have evolved in gamete recovery,
such as ultrasound, embryo transfer and embryo biopsy after assisted reproduction.
The amazing pictures that have been generated of gametes, fertilization, embryos,
and the reproductive tract in recent years would not have been possible without
9+T 0see At$as& Sathananthan et a$& 122<4

The paternal centrosome regulates cell division in the embryo and is the active
division centre. 9 maternal contribution is made in the zygote

THE SECOND 5EE6. Bi$a%inar e%(r'o. Deep i%p$antation
-ost things happen ;in twos< during this week.
1i3 /mbryoblast splits into two layers 1beginning of gastrulation3
1ii3 Two new cavities are formed5 amniotic and chorionic
1iii3 Trophoblast differentiates into cyto and syncytio*trophoblast
a) Bilaminar Embro
The embryo is discoidal and spherical and consists of two layers5 epiblast 1above3
and hypoblast 1below3 formed by delamination 1splitting3 of a single layer. The
hypoblast 1day >3 becomes the endoderm and the epiblast will later differentiate
into ectoderm and mesoderm 1week 3. The endoderm proliferates and lines the
blastocoele cavity 1?euserAs membrane3, now called the primitive yolk sac below
the embryonic disc 1day 83. There is no yolk in the human yet a yolk sac appears
as in yolky embryos, e.g. chick. ?owever, the yolk sac is vital for formation of
blood and germ cells.
b) !mnion and chorion and their ca"ities#
These two membranes are foetal 1e(traembryonic3 membranes while the yolk sac
is another. The conceptus at this stage can be regarded as being composed of
balloons amniotic sac above and yolk sac below, pressed against the embryonic
disc. The chorionic sac is the largest balloon on the outside 1trophoblast3, covering
the 2 sacs and the embryonic disc.
The Amnion5 The amnion appears on day 8 on the roof of the embryonic disc. 6luid
accumulates and a thin epithelium is formed from the cytotrophoblast. The epiblast
forms the floor of the amniotic cavity. This is the beginning of the water bag. The
amniotic cavity enlarges and by week 8 encloses the entire embryo.
The %horion5 The chorion is formed after the appearance of the e(traembryonic
mesoderm 1days 17H113. These cells arise from the epiblast and migrate to form
two layers the inner lining the ?euserAs membrane 1secondary yolk sac3 and the
other the inner surface of the cytotrophoblast which becomes the chorion. The
cavity formed is the e(traembryonic coelom or chorionic cavity 1days 12H13. The
chorionic cavity enlarges and the embryonic disc with its dorsal amniotic sac and
ventral yolk sac is suspended in the chorionic cavity by a connecting stalk of
mesoderm.
0,or ia8ra%s see Moore ?1232@; Lan8%an ?123A@; Larsen ?1223@4
c) $to% and snctiotrophoblasts &deep implantation)
The trophoblast has already differentiated into a cellular 1cytotrophoblast*%T3 and
syncytium
1syncytiotrophoblast*!T3 at the embryonic pole of the blastocyst. The !T is
invasive and helps the embryo implant in the endometrium. )eeper implantation
1days >*23 involves e(tensive growth of the conceptus and its complete
implantation within the endometrium, leaving a scar or blood clot 1closing plug3.
?ydrolytic enzymes secreted by the trophoblast digest the e(tracellular matri(
between the endometrial cells and processes of the trophoblast penetrate deep into
the endometrium. The !T grows all around the conceptus and lacunae or cavities
appear within it 1day 23. !oon maternal blood capillaries anastomose and invade
the lacunae establishing a primitive uteroplacental circulation. /(tensions of the
%T e(tend and grow into the overlying !T establishing the primary chorionic villi
1beginnings of the placenta3.

9 primitive uteroplacental circulation is established in week 2 not to be confused
with the placenta

d) $linical !pplications
Spontaneous Abortions5 These are 4uite common during early development. 9n
abortion is defined as a termination of pregnancy before 27 weeks of gestation.
9lmost all abortions that occur in the first weeks are spontaneous 1not induced3.
0t is estimated that $7I of all such abortions are caused by chromosomal
abnormalities. 0t is also reported that 7*$7I of zygotes never become blastocysts
and implant.
Hydatiform Mole5 6ew of the pregnancies result in hydatiform moles in which the
embryo is entirely missing and only a placenta is present. #rimary chorionic villi
are present without embryonic vessels detectable by ultrasound. %omplete moles
have "& chromosomes, all of paternal origin because zygotes have two male
pronuclei. #artial moles are formed from triploid dispermic zygotes. 'oth types of
moles tend to abort spontaneously or are surgically removed. #ersistent molar
tissue may result in trophoblastic disease.
THE THIRD 5EE6. Tri$a%inar e%(r'o 9 for%ation of 8er% $a'ers.
The most dramatic event in early development is the formation of the primary
germ layers5 ectoderm, endoderm and mesoderm referred to as gastrulation in
animal terms. 0t is from these germ layers that all the tissues and organs of the
human body are formed. 'asically, ectoderm forms the skin and nervous system
1outside3, endoderm the gut and associated glands including the respiratory system
1inside3, while mesoderm forms all the other organ systems 1in between@.
0,or etai$s of eri#ati#es of 8er% $a'ers see Moore ?1232@4

The most dramatic event in early development is the formation of ectoderm,
endoderm and mesoderm, the three germ layers referred to as gastrulation

'rimiti"e streak: Mesoderm formation
The embryonic disc now becomes pear*shaped and develops a linear primitive
streak, dorsally in the epiblast, which is a heap of cells that proliferate and migrate
to the centre line. 0t appears first at the caudal end at the beginning of week and
grows towards the centre of the disc. The primitive streak 1day 1&3 signals the
formation and separation of mesoderm from the ectoderm overlying it. 0t may be
likened to a permanently closed keyhole, where cells migrate inwards, sideways
and forwards to form the mesoderm sandwiched between the ectoderm and the
endoderm 1hypoblast3 which was formed in week 2. This is best appreciated in
transverse sections of the disc. EEB!e$$ent :/D i%a8es of the pro!ess& as =e$$ as
se!tions& are presente in Lan8%an ?1231@; Moore ?1232@; Larsen ?122:@. The
process of mesoderm formation is called ;immigration<, while endoderm
formation is referred to as ;delamination<. 'oth processes result by differentiation
and movement of cells to take up their definitive positions in the embryo, of course
regulated by the genes on the chromosomes of maternal and paternal origin. The
genes control the process of development before and after birth. Thus cell
differentiation and cell movements are integral processes of development it is
important to put the right cell in the right place at the right time to ensure normal
development. 9ny disturbances in this co*ordinated interaction of cells will
eventuate in abnormal development. 'oth genetic and environmental factors are
involved in many developmental processes. -orphogenesis 1the development of
comple( from simple structure3 is regulated by cascades of gene e(pression. 9t
first the maternal genes are switched on, which then activate the zygotic genes.
0mportant events such as gastrulation are controlled by such genes. The embryo is
now trilaminar and after all mesoderm cells have migrated along the primitive
streak it regresses to the caudal region of the embryo and degenerates. 0f it persists
a tumor or teratoma is formed.

Castrulation involves proliferation, differentiation and movement of cells within
the embryo

(eurulation and formation of the notochord
Beurulation involves the formation of the neural plate and tube 1primitive nervous
system3. This is preceded by formation of a hollow rod of cells beneath the
ectoderm as the primitive streak recedes. The mesoderm cells that migrate through
the primitive knot 1cranial end of streak3 become the notochordal process. This is
later transformed into a solid rod the notochord, the embryonic a(ial skeleton *
which is replaced by the vertebral column. ,n day 1> the notochordal mesoderm
induces the overlying ectoderm to form the neural plate. This is a good e(ample of
chemical induction where one tissue induces the formation of another.
(eural tube formation
9t first the neural plate is oval but later elongates over the underlying notochord
along the whole a(is
of the embryo. The plate invaginates towards the notochord to form a neural
groove, which deepens progressively to form a tube by fusion of the lateral neural
folds. This nerve tube is hollow and is lined by pseudostratified columnar
epithelium. The cells of the neural crest separate from the tube to develop into the
spinal and autonomic ganglia and pigment cells, later. The nerve tube is formed on
days 12*21, and its closure begins in the middle of the embryo and progresses
towards cranial and caudal ends by the end of week ". The anterior end swells to
become the brain and the rest forms the spinal cord. The neural tube is open
cranially and caudally, forming the neuropores, which close in week ".

The neural tube forms the central nervous system brain and spinal cord.

)e"elopment of somites
!omites are blocks of para(ial mesoderm which appear in pairs on either side of
the notochord. The first somite appears on day 27 behind the base of the future
skull. This is the first sign of segmentation in the embryo. !ubse4uent somites
form behind the first progressively till "2*"" pairs are formed by week "H$. The
number of somites are used to determine the age of the embryo. The somites give
rise to most of the a(ial skeleton, associated musculature and dermis of the skin.
The intraembryonic coelom 1body cavity3 is formed in mesoderm lateral to the
somites.

!omites are blocks of mesoderm used to determine embryonic age

Formation of heart and blood "essels
The rudiments of the heart and blood vessels are also laid down in week . 'lood
vessels are formed in the mesoderm of the yolk sac and chorion as spaces within
mesenchyme cells 1blood islands3. They are soon lined with endothelium, and unite
with other vessels to form a primitive cardiovascular system. The heart is formed at
the end of week in much the same way as enlarged blood vessels in the cranial
region. #aired heart tubes are formed which begin to fuse to form a primitive heart,
which connects up with blood vessels in the embryo, chorion and yolk sac. The
heart begins to beat and the vascular system is the first to become functional.
0A ia8ra% of the pri%iti#e #as!u$ar s'ste% is sho=n in Moore& 12324
!llantois
The fourth foetal membrane appears in week as a diverticulum of the yolk sac
1caudal wall3. 0t remains small and is also involved in angiogenesis 1formation of
blood vessels3 and is later associated with the development of the urinary bladder.
$horionic "illi
The primary chorionic villi have a core of connective tissue and eventually develop
blood capillaries and become secondary and tertiary villi and cover the entire
surface of the chorion 1see placenta3. Their vessels also connect up with vessels
inside the embryo. Butrients and other substances are e(changed between maternal
and foetal circulations.

'lood vessels are formed in the mesoderm of the yolk sac, chorion and allantois.

$ongenital malformations
)isturbances in neurulation cause some abnormalities of the brain and spinal cord.
6ailure of
closure of the neural tube in the caudal region 1caudal neuropore3 results in spina
bifida. These defects also involve the tissues overlying the spinal cord 1meninges,
vertebral arches, dorsal musculature and skin3. The most fre4uent site of failure of
neurulation is the cranial neuropore resulting in anencephaly.

5EE6S C 9 3.CRITICAL -ERIODS O, DE+ELO-MENT. ,or%ation of a$$
%aDor or8an rui%ents an the e%(r'oni! (o'
The last $ weeks of embryonic development are very critical since all the main
organ systems are laid down, both e(ternally and internally, and the embryo takes
shape and finally takes the characteristic human form by week 8. 0t is a critical
period since ma.or developmental disturbances that occur now could result in
ma.or congenital malformations in each system of the human body. )uring this
period the embryo is susceptible to teratogens 1agents that induce malformations3.
0A s!he%ati! i$$ustration of !riti!a$ perios for so%e or8ans is presente in
Moore ?1232@4

-a.or congenital malformations may occur during the critical periods of
development.

Formation of the embronic bod: Folding and Fle*ion
Jp to the end of week the embryo was a flat disc. 0n week ", the embryo grows
very rapidly and becomes progressively cylindrical and takes a characteristic %*
shaped form, common to vertebrate embryos. This is caused by folding of the
embryo, cranially, caudally and laterally, at the same time positioning and
demarcating some of the organs within the embryo.
The effects of folding can best be seen in longitudinal and transverse sections of
embryos Esee Dangman 112813G -oore 112823G Darsen 11223K. ?ead and tail
fle(ion occurs ventralwards during week ", raising and demarcating the embryonic
body from the disc. The developing brain grows cranially, tucking the heart and
future mouth cavity ventrally. #art of the yolk sac is incorporated into the embryo
as the foregut. !oon the tail fold at the caudal end pro.ects over the cloacal region
and incorporates part of the yolk sac as the hindgut. 9fter folding, the connecting
stalk and yolk stalk remain attached to the ventral surface of the embryo as the
umbilical cord. !imultaneously the lateral folds establish the almost cylindrical
form of the rest of the embryo best visualized in transverse sections. 9s the
lateral folds grow medially, the roof of the yolk sac is incorporated into the embryo
as the midgut, and the yolk sac is reduced to a narrow yolk stalk. The somites
differentiate into sclerotome, myotome and dermatome components internally and
are prominent e(ternally.

The embryonic body is formed by fle(ion and folding resulting in a cylindrical
embryo.
The % shaped embryo, thus formed, undergoes further fle(ion and growth in
weeks $ and &. 0t develops fore and hind limb buds and a heart prominence in the
chest region. The eye develops on the sides of the forebrain region and " branchial
arches appear on the sides of the foregut region 1pharyn(3. The brain has divided
into fore, mid and hind brain compartments and is demarcated from the rest of the
spinal cord. The somites 1*$ pairs3 become more prominent on either side of the
spinal cord evidence of segmental development. The head has grown much larger
than the body in week & due to the growth of the brain. The forelimb develops
digital rays future digits. The e(ternal auditory meatus 1ear3 appears where the
first branchial groove is located. The peripheral nervous system begins to form,
integrating the developing nervous system. Beural crest cells migrate from the
neural tube and aggregate to form ganglia of the sympathetic nervous system and
the sensory spinal ganglia.

The embryo is %*shaped like most other vertebrate embryos, when they look
similar.

)uring the weeks > and 8 limbs have formed, the fingers of the hand have
separated and the feet are webbed, which then separate into toes. The tail stub
disappears altogether. The head is more round and erect but is disproportionally
large. The abdomen is flatter but the intestines have herniated in the pro(imal
region of the umbilical cord. /yelids have formed and are usually open. The
auricles of the e(ternal ear have formed. The head has enlarged immensely and the
embryo is now un4uestionably human in appearance.
)etermination of Embronic !ge and Measurement
Two criteria are used to determine day 1 in the natural cycle to estimate age5* time
of fertilization or onset of last menstrual cycle. The latter becomes complicated for
those who have discontinued oral contraception. The day of fertilization is the most
reliable for estimating age and this is easily determined by the time of ovulation =
12 hours, which is the timeframe within which the egg is fertilized. 0n vitro,
estimation is easier, since fertilization occurs 2 hours after insemination and
pronuclei are formed 12 1& hours after insemination 0see at$ases& Sathananthan
et a$& 122:;122<4 /mbryonic age is determined from e(ternal features and
measurement of length, usually after abortions. Their greatest length , crown
rump length 1sitting height3 or crown heel length are often used. -ore accurate
measurements can be made in utero by ultrasound at weeks " $, when e(ternal
structures can be visualized. 0See Moore& 1232& for %easure%ents an ta($es4
+nternal differentiation: ,rganogenesis
The germ layers formed from the inner cell mass in week give rise to all the
tissues and organs of the human body. %ells of each germ layer proliferate,
migrate, reaggregate and differentiate into various tissues that form the organs
1organogenesis3
Ectoderm This outermost layer forms the epidermis of the skin and glands, the
central nervous system 1brain and spinal cord3, peripheral nervous system 1nerves
and ganglia3, and the sensory epithelia 1eye, ear and nose3.
Mesoderm This intermediate layer forms the ma.ority of tissues and organs5
connective, skeletal, muscular tissues, cardiovascular, urinary and reproductive
systems, body cavities and linings and the spleen.
Endoderm This innermost layer forms the epithelium of the gastro*intestinal and
respiratory systems and associated glands 1liver and pancreas3, epithelial lining of
urethra and parts of the ear, thyroid, parathyroid and tonsils.

%ritical periods for most organ systems generally range from 8 weeks of
development, when the rudiments are laid down. Teratogens kill the embryo in the
first two weeks or damage some cells
allowing the embryo to recover 0see Moore& 12324

The germ layers give rise to all the tissues and organs of the human body.

-HYSIOLOGY O, THE EMBRYO. -$a!entation
The placenta is an organ derived from the trophoblast of the blastocyst and is
composed of some foetal
membranes. These membranes are mostly e(traembryonic and consist of the
amnion, chorion, yolk sac and allantois, which combine to various degrees to form
the placenta and umbilical cord. ?umans are placentals and the foetal placenta is
allanto*chorionic , with the villous chorion forming the ma.or part of the organ. 0t
is essentially involved in the physiology of the embryo and has many functions5*
protection, nutrition, respiration, e(cretion and also has an endocrine function
producing hormones. The term conceptus refers to the embryo plus the foetal
membranes.
The decidua#
The placenta has both foetal and maternal components. The maternal portion is the
gravid 1pregnant3 endometrium, which is cast off at birth 1parturition3 hence
termed decidua. The decidua are named acccording to their relation to the
implantation site5* a3 )ecidua basalis underlying the conceptus forming the
maternal componentG b3 )ecidua capsularis the superficial wall overlying the
conceptusG c3 )ecidua parietalis the remaining uterine mucosa or wall. 9s the
conceptus grows, the capsularis bulges into the uterine cavity and fuses with the
parietalis, obliterating its cavity. The capsularis degenerates and disappears by
about week 22. The basalis forms the maternal placenta and is usually discoidal in
shape.
)e"elopment of the placenta
Fe have already dealt with the origins of the foetal membranes in weeks 2 and . 0t
is by week " that the essential parts of the placenta are established and become
functional. 'y weeks 27 22 it is fully formed 0see Moore& 1232& for ia8ra%s4.
0t is the chorionic villi, embedded in the decidua basalis, that are involved in foeto*
maternal e(changes, later on.
Jntil about week 8, the chorionic villi 1%83 cover the entire surface of the
chorionic sac. /ventually the villi over the decidua capsularis degenerate due
to reduced blood supply, forming the smooth chorion. Those %8 associated
with the decidua basalis persist, multiply and branch profusely to form the
villous chorion, the foetal placenta. The foetal component is thus composed
of the chorion and its %8 that are bathed in the maternal blood hence
called a haemo*chorial placenta. The villous chorion, composed of tertiary
villi, is anchored to the maternal decidua basalis by anchoring villi. The full
term placenta has a very complicated structure composed of branched %8
with foetal blood vessels embedded in the decidua basalis. The %8 are
bathed with maternal blood filling the intervillous spaces, flowing from the
endometrial spiral arteries, in spurts.
0See Moore& ?1232@; Lan8%an& ?1231@4

The chorionic villi are the chief components of the foetal placenta.

$horionic "illi : -illous chorion
#rimary %8 were formed on day 1" when a primitive utero*placental circulation
became functional. These had a core of cytotrophoblast 1%T3 surrounded by
syncytiotrophoblast 1!T3. The core is eventually invaded by e(traembryonic
mesoderm, which becomes mesenchyme or connective tissue 1secondary villi3 and
later by foetal capillaries formed in week 1tertiary villi3. These have both %T and
!T covering the villus. The full*term %8 has an epithelium of !T with little or no
%T and several foetal capillaries. The whole theme in this development is to make
the barrier between the foetal and maternal blood as thin as possible, to increase
the efficiency of foeto*maternal e(changes. Thus we have arrived at the most
efficient placenta in mammalian evolution and the barrier is called the placental
membrane.0An eB!e$$ent ia8ra% sho=in8 the e%(r'oni! an #i$$ous
!ir!u$ator' s'ste% is sho=n in Moore ?1232@4.
The placental membrane: -illus.
This membrane consists of " layers that separate the foetal from the maternal
blood5* foetal capillary
endothelium, foetal connective tissue, %T and !T. The %T is scanty and the
maternal blood bathes the villus. 'y full term, the foetal capillaries are brought
very close to the maternal blood, there being little or no intervening connective
tissue.

The placental membrane separates the foetal from the maternal blood.

Foeto%maternal e*changes#
The placenta has three main functions metabolism, transfer and endocrine. -any
substances can permeate the placental membrane. These include gases 1,
2
and
%,
2
3 by diffusionG nutrients 1glucose, fatty acids, amino acids, water, electrolytes,
vitamins35 foetal waste products 1%,
2
, urea, uric acid3G some hormones and
antibodies 10gC3 and harmful substances such as drugs, poisons, teratogens,
alcohol, tobacco, cocaine, viruses 1rubella3 and the syphilis bacterium. -ost
bacteria and heparin cannot cross the membrane. ?08 could be transmitted across
the placenta during childbirth or by breastfeeding. The placenta also produces
steroid hormones 1progesterone and estrogen3, human chorionic gonadotrophin
1h%C3 and other protein hormones and prostaglandins. 6oetal h%C is e(creted in
the motherAs urine and is the basis for the pregnancy test.

THE UMBILICAL CORD
The vascular life*line of the embryo and foetus is the umbilical cord which
connects them to the
placenta. 0t is gradually formed after week ", replacing the connecting stalk and
attains a cord*like form by week 27. 0t is derived from foetal membranes,
amnion, yolk sac and allantois, and the cord takes shape during e(tensive growth
of the amniotic cavity 0(est #isua$i7e in ia8ra%s/see Moore& 12324. 0t is
composed of gelatinous mesenchyme called FhartonAs .elly and usually contains 2
arteries and 1 vein. The cord usually connects up near the centre of the discoidal
placenta. Lnotting or looping of the cord could be dangerous to the foetus,
especially if it is around the neck. 0t may impede circulation and cause death.

The umbilical cord is the life*line of the embryo and foetus

THE ,OETAL MEMBRANES. -h'sio$o8' of the e%(r'o.
There are " foetal membranes5* chorion, amnion, yolk sac and allantois. They are
e(traembryonic in origin and are composed of either ectoderm or endoderm
combined with mesoderm. They play an important role in the functioning of the
embryo and contribute to the formation of the placenta, as well.
a) !mnion and !mniotic Fluid#
The amnion or waterbag forms a fluid*filled sac around the embryo and its chief
functions are protection, providing an ancient watery environment, and preventing
dessication. 9ll vertebrate embryos develop in a watery environment and the
human is no e(ception. 9mniotic fluid is derived from the maternal blood and later
the foetus e(cretes urine into the fluid. The fluid is also swallowed by the foetus
and absorbed in the gut. The embryo floats freely in the fluid, permitting growth
and free movement. 0t cushions the embryo and acts as a shock absorber. 6urther it
prevents adherence of membranes and limbs and maintains a constant body
temperature.
b) .olk Sac
Though the human egg has no yolk, it forms a yolk sac, like the chicken embryo. 0t
develops in week 2 as a sac and is later reduced to a pear*shaped vestige 1week $3.
0ts functions are5* 1i3 transfer of nutrients in weeks 2 and when the utero*
placental circulation is establishedG 1ii3 'lood islets form in the mesoderm of the
yolk sac wall in week 1hemopoietic activity3G 1iii3 The roof of the yolk sac forms
the primitive gut 1week "3G 1iv3 #rimordial germ cells appear in the wall of the yolk
sac, which later migrate to gonads to become germ cells.

c) The !llantois
9ppears in week as a small diverticulum in the hindgut region of the embryo and
grows into the connecting stalk. 0t is non*functional as an embryonic bladder in
human embryos but is involved in the formation of blood during the first 2 months
and the allantoic blood vessels become the umbilical vessels. The allantois also
forms the urachus connected to the bladder which becomes the median umbilical
ligament after birth.
d) The $horion
This is the most important foetal membrane, since it forms the foetal placenta
villous chorion, which we have already dealt with. 9bove all it is the outermost
membrane covering both the embryo and other foetal membranes. ?ence it also
has an overall protective function apart from its placental function. 6oetal
membranes are e(tra*embryonic and are involved in the functioning of the embryo
and foetus.

T5INS AND MULTI-LE -REGNANCIES
-ultiple pregnancies will be dealt with in another chapter. ?owever, with respect
to foetal membranes, twins may share the amnion or chorion and even the placenta,
depending on whether they are dizygotic or monozygotic. 0f dizygotic blastocysts
1originating from 2 zygotes3 implant close together, they may share the same
placenta. -onozygotic twins 1originating from 1 zygote by division of the inner
cell mass3 usually have a single chorion and a common placenta. -onozygotic
twins formed by division of the embryonic disc in week 2 share a single amniotic
sac, a chorionic sac and a placenta. The twins may be separate or con.oined
1!iamese3 or may be parasitic, depending on complete or incomplete division of
the embryonic disc. -onozygotic twins are rarely delivered alive since their
umbilical cords are entangled when circulation stops and foetuses die. Twins are
usually smaller than a single foetus, since crowding interferes with growth and
nutrition. 0See Moore& 1232& for ia8ra%s an photo8raphs4

SELECTED RE,ERENCES

Lan8%an *. -edical embryology 16ourth /dition3 1281G Filliams M Filkins,
'altimore. pp 8".
1%oncise te(t with colour diagrams and photographs.3
Larsen 5*. ?uman embryology 122G %hurchill Divingstone, Bew Nork. pp ">2
19dvanced te(t with colour illustrations and clinical applications3
Moore 6L. 'efore we are born5 basic embryology and birth defects 1Third
/dition3 1282G !aunders, #hiladelphia. pp 7&.
1!imple te(t with colour illustrations and photographs3
OERahi$$' RA. %olour atlas of human embryology 12>$G !aunders, #hiladelphia.
1%omprehensive set of $ mm slides the real thing5 whole embryos and sections.3
Sathananthan AH& N8 SC& Bon8so A& Trounson A& Ratna% SS. 8isual atlas of
early human development for assisted reproduction technology 122. Bational
Jniversity, !ingapore. pp 272
1#re*implantation development5 illustrations and microphotographs.3
Sathananthan AH 1ed.3. 8isual atlas of human sperm structure and function for
assisted reproduction technology 122&G Bational Jniversity, !ingapore. pp2>2.
1-icroscopical images of gametes, fertilization and zygotes, some in colour.3
Sathananthan AH& E=ars RG. 6rom sperm binding to syngamy computer
enhanced images of human fertilization 1%)*+,-3 122$G ?uman +eproduction
Jpdate 151