Chapter 19 INTRODUCTION TO EMBRYOLOGY
Ⅰ. Embryology is a science that studies the normal development as well as the birth
defects of a human being in the maternal uterus.
Ⅱ. Normal development -- takes 38 weeks from fertilization to parturition of a mature fetus.
Three periods are divided:
A. Preembryonic period: First two weeks -- fertilization to formation of the bilaminar germ
B. Embryonic period: Weeks 3 – 8. Primordia of all major organs are developed from the
3 germ layers.
C. Fetal period: Week 9 – birth -- growth of the organ systems.
Ⅲ. Birth defects -- structural and functional defects present at birth. The study of the
congenital molformations is the teratology.
1. Chromosomal and genetic factors (25%)
a. Numerical abnormalities of chromosomes
Autosomes: Trisomy 21 (Down’s syndrome), etc.
Sex chromosomes: XXY (Klinefelter’s syndrome),
XO (Turner’s syndrome), etc.
b. Structural abnormalities of chromosomes: break, deletion, insertion, etc.
e.g. 5p- → cat cry syndrome
c. Genetic mutations (change in composition or sequence of the bases in DNA)
usually cause metabolic or functional disorders (e.g. phenylketonuria,
galactosemia), and a few malformations are seen (e.g. polycystic kidney,
achondroplasia, microcephaly, etc.)
2. Environmental factors (teratogens) (10%)
Viruses: rubella virus, cytomegalovirus, herpes simplex virus;
b. Physical: radiation, mechanical pressure, traumas, etc.
Chemicals: nitrites, mercury, lead, etc.
Drugs: thalidomide (Amelia, meromelia),
aminoptrin (anencephaly, hydrocephalus, cleft lip),
streptomycin (deafness), etc.
Social drugs: cigarettes (small babies),
alcohol (fetal alcohol syndrome).
Hormones: estrogens, progestins.
d. Others: hypoxia, nutritional deficiencies.
3. Interaction of genetic and environmental factors (65%)
B. Susceptible period
1. The susceptible period to teratogenic factors generally is the embryonic period (3 –
8 weeks), because intensive differentiation occurs in this period.
2. Different organs have different susceptible period corresponding to their own critical
3. Different teratogens also have different susceptible period.
Chapter 20 EARLY DEVELOPMENT OF HUMAN EMBRYO
Ⅰ. Gametogenesis -- A process of formation and maturation of the gametes (spermatozoa in
male and ovum in female)
A. The purposes of gametogenesis
1. Reduction of the number of chromosomes to half by meiosis, which occurs only in
2. Alteration of the shape of germ cells for fertilization.
mitosis Primary meiosis
Spermatogonium spermatocyte 4 Spermatids
( 2n ) (puberty) ( 2n: 46,XY ) ( n: 23,X; 23,Y )
spermiogenesis full motility capacitation
4 Sperms 4 Sperms
(n) ( epididymis ) ( uterus, tube )
4 Sperms (motile and ready for fertilization)
2. Functional mature: During transportation in the epididymis, the spermatozoa
gradually get the ability of the forward movement and the potential of fertilizing the
eggs under the influence of substances secreted by the epididymis epithelium.
3. Capacitation: A process of the spermatozoa obtaining capacity of fertilizing an egg.
Capacitation occurs in the female reproductive tract (uterus, oviduct) probably
through the removal of a glycoprotein coat from the plasma membrane of the
mitosis meiosis 1 polar body
Oogonium Primary oocyte Secondary oocyte
( 2n ) ( fetal ) (2n: 46,XX ) ( puberty ) ( n: 23, X )
meiosis 2 polar body
( fertilization )
Ⅱ. Fertilization To Implantation (First Week of Development)
A. Fertilization -- A process of union of a sperm from male and an ovum from female to
form a fertilized egg (zygote)
1. Time: 12 - 24 hours after ovulation.
2. Site: the ampulla of the uterine tube.
3. Process: Acrosome reaction → Sperm penetrating corona radiata andzona pellucida
→ Fusion of oocyte-sperm cell membrane → Entry of only one sperm into the
cytoplasm of the oocyte → Oocyte finishing meiotic division 2 and forming the
female pronucleus → Formation of male pronucleus → Two pronuclei meeting and
chromosomes from both organizing on the spindle, and then the first cleavage
a. Normal development, transport and viability of male and female gametes;
b. Two gametes meet in due time.
a. Restoration of the diploid of number of chromosomes.
b. Determination of the sex: Y+X = male, X+X = female.
c. Activation of egg metabolism and initiation of cleavage.
B. Cleavage and blastocyst formation
1. Cleavage is a series of mitotic divisions of the fertilized egg. A number of smaller
cells called blastomeres are produced.
2. After 3 - 4 days of fertilization, the embryo consists of a solid ball of 12 - 16 cells within
the zona pellucida and called the morula, and enters the uterine cavity.
3. Intercellular spaces containing fluid appear and become confluent to form a single
cavity, the blastocele, the embryo is now known as the blastocyst.
4. The cells are then arranged in
a. a group of cells at the embryonic pole, the inner cell mass (or embryoblast),
which will develop into the embryo proper.
b. a surrounding layer of flattened cells, trophoblast, which absorb nutrients.
C. Implantation -- A process of the blastocyst embedding into the endometrium
1. Time: Starting at about the 6th day and finishing at the 11th or 12th day.
2. Site: Along the posterior or anterior wall of the body of the uterus.
3. Process: Zona pellucida disappears → Polar trophoblast cells contact with the
endometrium and invade it by proteolytic enzymes → Blastocyst sinks deep into the
endometrium → Site of invasion is sealed over.
a. Zona pellucida disappears in time.
b. Normal development and transport of the young embryo.
c. Endometrium in the secretory phase and with a normal decidual reaction.
d. Normal endocrine regulation of estrogen and progesterone.
5. Decidual reaction: Around implantation the endometrium is morphologically changed
and known as the decidua, which provides nourishment for the embryo and protects
the maternal tissue from excessive invasion by trophoblast.
a. Decidua basalis: beneath the implanted blastocyst and forming the maternal
component of placenta.
b. Decidua capsularis: over the blastocyst.
c. Decidua parietalis: all the remaining endometrium.
6. Abnormal implantation:
a. Placenta previa: Implantation near the internal os. The placenta overbridges the
os and causes severe bleeding during later pregnancy and delivery.
b.Ectopic pregnancy: Implantation outside the uterus. This may occur at the uterine
tube, abdominal cavity, or ovary, and leads to abortion and severe hemorrhaging
by the mother during the 2nd month of gestation.
Ⅲ. Bilaminar Germ Disc (Second Week of Development)
A. Differentiation of two distinct layers of cells from the inner cell mass.
1. Epiblast -- layer of columnar cells adjacent to the trophoblast.
2. Hypoblast -- layer of cuboidal cells facing the blastocele.
3. Each of the germ layers forms a flat disc and together they are known as the
bilaminar germ disc.
B. Development of chorion from the trophoblast
1. Trophoblast cells proliferate and form two layers: inner layer of mononucleated cells,
the cytotrophoblast; outer layer of multinucleated cells without distinct cell
boundaries, the syncytiotrophoblast or syncytium.
2. Cytotrophoblast cells proliferate inward and form a loose layer of cells called the
extraembryonic mesoderm. Later a large cavity occurs in the extraembryonic
mesoderm, the extraembryonic or chorionic coelom. The remaining
extraembryonic mesoderm that connects the embryonic disc and trophoblast forms
the connecting (or body) stalk.
C. Formation of two new cavities
1. Amniotic cavity -- A small cavity appearing within the epiblast, the roof of which is
lined with amnioblasts and the floor is the epiblast.
2. Yolk sac
a. The hypoblast cells proliferate and form a thin membrane, exocoelomic (Heuser’s)
membrane, which lines the inner surface of the cytotrophoblast. This membrane,
together with the hypoblast, forms the primary yolk sac (exocoelomic cavity).
b. The hypoblast later produces additional cells that migrate and form a new cavity,
called secondary yolk sac within the primary yolk sac, which gradually
Ⅳ. Trilaminar Germ Disc (Third Week of Development)
A. Formation of primitive streak
1. Proliferation of epiblastic cells in the middle of the caudal part of embryonic disc
forms a cell cord, the primitive streak, with a swelling cephalic end, the primitive
node. Both the streak and node have a depression in the middle line, called the
primitive groove and primitive pit, respectively.
2. The primitive streak determines the caudal end and symmetrical axis of the germ
B. Formation of mesoderm
1. Cells of the epiblast proliferate and migrate in the direction of the primitive streak. On
arrival in the streak, they move in between the epiblast and hypoblast and spread
laterally and cephalically to form a new germ layer, intraembryonic mesoderm.
2. Two regions have no mesoderm, the prochordal plate (future buccopharyngeal
membrane) and the cloacal membrane.
C. Formation of trilaminar germ disc
1. With the mesoderm formation, the epiblast cells also move in the hypoblast and take
place of it forming the endoderm. Cells remaining in the epiblast comprise the
ectoderm. The embryo is now a trilaminar germ disc.
2. All 3 germ layers are derived from the epiblast.
D. Formation of notochord
1. The epiblast cells invaginating in the primitive pit move straight cephalically to form a
tube-like process, the notochordal or head process,which later forms a solid cord,
known as notochord.
2. Although gradually degenerating, the notochord is important in inducing the formation
of the nervous system.
E. Formation of allantois: Allantois is a small tube projecting from the caudal part of the yolk
sac into the body stalk.
Ⅴ. Differentiation of Germ Layers and Establishment of Body Form (3th to 8th Week of
A. Differentiation of ectoderm
1. Neural ectoderm
a. The ectoderm over the notochord thickens forming the neural plate.
b. The neural plate invaginates along its central axis forming the neural groove, and
the lateral edges of the neural plate elevate and form the neural folds.
c. The neural folds move closer and begin to fuse in the region of the future neck and
extend cephalically and caudally forming the neural tube, which is the
primordium of the central nervous system, including the retina and optic
d. Some cells of the neural folds are not incorporated into the tube and form neural
crests, which produce the peripheral nervous system, the chromaffin cells of the
adrenal medulla, melanocytes, and parafollicular cells of the thyroid.
e. Failure of closure of the cephalic end and caudal end of the neural tube causes
the anencephaly and myeloschisis, respectively.
2. Surface ectoderm: differentiating into the epidermis and hair, nails, sweat glands,
sebaceous glands and mammary glands; the adenohypophysis; the sensory
epithelium of the ear, nose, tongue; the lens of the eye and the enamel of the teeth.
B. Development of mesoderm -- the mesoderm soon differentiates into 3 regions:
1. Paraxial mesoderm: immediately lateral to the midline and thick. Later it breaks up
into blocks of cells, the somites (3 pairs/day, 42 – 44 pairs in total). The somites are
then divided into 3 portions: the sclerotome, dermatome and myotome. They
develop into the paraxial bones, muscles and dermis.
2. Intermediate mesoderm: lateral to the paraxial mesoderm and is the primordium of
the urogenital system forming the kidneys and gonads, etc..
3. Lateral mesoderm: at the periphery.
a. Spaces appear and coalesce in the lateral mesoderm forming a cavity, the
intraembryonic coelom, which develops into the body cavities. The coelom
divides the lateral mesoderm into 2 layers.
b. Somatic mesoderm covering the ectoderm develops into the bones, muscles
and connective tissue of the body wall, and the mesothelium lining the inner
surface of the wall.
c. Splanchnic mesoderm covering the endoderm develops into the muscles and
connective tissue of the viscera, and the mesothelium covering them.
C. Folding of the embryonic disc into a cylindrical embryo
1. As a result of the rapid growth of the central nervous system, the embryonic disc folds
cephalocaudally, the head and tail folds. Folding of the sides of the disc (lateral
fold), because of the rapidly growing somites, ventrally toward the midline forms a
2. As a result of folds the embryo bulges into the enlarged amniotic cavity. The surface
of the embryo is wrapped by the ectoderm and the endoderm forms a tube like gut
invested into the embryo. The body stalk is reduced to form the umbilical cord, by
which the embryo is suspended in the amniotic cavity.
D. Formation of primitive gut and differentiation of endoderm
1. With folds of the germ disc, the endoderm is invested into the body of the embryo
proper forming the primitive gut. Primitive gut is divided into the foregut, the
hindgut and the midgut. The latter remains in connection with the yolk sac by a
2. The primitive gut is the primordium of the digestive and respiratory systems. The
endoderm of the gut will form the epithelial lining of the digestive and respiratory
tract, and urinary bladder and urethra. It also forms the parenchyma of the liver,
pancreas, tonsil, thyroid, parathyroids, and thymus, and epithelium of the tympanic
cavity and Eustachian tube.
1. All the main organ systems have been established and the major features of the
external body form are recognized by the end of the 8th week.
2. Summary of differentiation of the three germ layers
a. Ectoderm: central and peripheral nervous system; epidermis of the skin,
including its appendages.
b. Endoderm: mucosal and glandular epithelia of the digestive and respiratory
c. Mesoderm: all connective tissue; all muscle tissue; vascular system; lymphoid
organs; urogenital system.
Ⅵ. Fetal Membranes and Placenta
A. Fetal membranes -- include chorion, amnion, yolk sac, allantois and umbilical cord.
1. Chorion -- made up of the syncytiotrophoblast, cytotrophobalst and mesoderm with
a. Development of villi: primary stem villi → secondary stem villi → tertiary stem
villi (with free villi later).
b. The chorion adjacent to the decidua basalis is called the chorion
frondosum, the villi of which are numerous, large and branched profusely. This
chorion forms the fetal component of the placenta.
c. The chorion associated with the decidua capsularis is the chorion laeve, the villi
of which become degenerated.
d. Excessive proliferation of the trophoblast may lead the hydatidiform mole with
large amounts of vesicles and dead embryo. The malignant proliferation of
trophoblast cells is called the chorion carcinoma.
2. Amnion -- thin, transparent membrane made up of an amniogenic cell layer and
outer extraembryonic mesoderm layer.
a. It forms the wall of the amniotic cavity. With folding of the embryo and expanding
of the amniotic cavity, it fuses with the chorion and covers the surface of the
umbilical cord and fetal surface of placenta.
b. Amniotic fluid, the clear watery fluid, is contained in the amniotic cavity and about
1- 1.5 liter at full term. Its functions are to:
1) provide a protective cushion and absorb jolts;
2) allow for fetal movement and prevent adherence of the fetus;
3) maintain body temperature of the embryo (or fetus);
4) help to dilate and clean the cervical canal making childbirth easier.
c. Amniotic fluid is produced by secretion of amniotic cells and filtration of maternal
blood. Later fetal urine is added to it. Amniotic fluid also filtrates into maternal
blood and is swallowed by the fetus.
d. A marked increase in tne volume of amniotic fluid (>2 liter) is called
polyhydramnios, suggesting a malformation of anencephaly, hydrocephalus,
or esophageal atresia. A marked decrease of amniotic fluid (<500 ml) is
oligohydramnios, due to renal agenesis or urethral atresia.
3. Yolk sac -- an endoderm-lined cavity with an outer extraembryonic mesoderm layer.
Its significance in development is:
a. Some endoderm cells of it form primordial germ cells.
b. Mesoderm cells of its wall differentiate into primitive blood cells.
4. Allantois -- a diverticulum from the caudal part of the yolk sac extending into the
body stalk. Its significance is that the blood vessels in its wall later become umbilical
arteries and vein.
5. Umbilical cord -- a cord devired from the body stalk and connecting the embryo or
fetus to placenta
a. At first It contains the body stalk, allantois, umbilical vessels, and vitelline duct
Later the allantois and vitelline duct are obliterated, and the cord contains only 2
arteries and 1 vein surrounded by jelly-like mucoid connective tissue.
b. At birth, it is about 2 cm in diameter and 50 cm long. A very long cord may
encircle the neck or extremity of the fetus. A very short one may pull the placenta
during labor causing its premature detachment from the uterine wall and bleeding.
1. The placenta consists of fetal and maternal portions, the former being formed by the
chorion frondosum and the latter being the decidua basalis.
2. At full term it is discoid about 15 -20 cm in diameter, 2.5 cm thick and 500 g in weight.
Its fetal side is smooth with the cord attached in the center. The maternal side is
rough with 15 - 30 slightly bulging areas, the cotyledons.
3. Three layer structure:
a. The chorionic plate projects out the stem villi anchoring to the decidua by the
b. The basal plate is made up of the decidua basalis from which the placental septa
extend and divide the placenta into a number of cotyledons.
c. In between both plates, are free villi branched from the stem villi and bathed in the
intervillous spaces, which are filled with maternal blood and lined with
4. The fetal blood in the villi is separated from the maternal blood in the intervillous
spaces by the placental membrane or barrier, which is composed of 4 layers:
a. Endothelium and its basal lamina of the villous capillary.
b. Connective tissue in the core of the villus.
c. Cytotrophoblast and its basal lamina.
d. Syncytiotrophoblast layer.
As the pregnancy advances, the placental membrane becomes much thinner,
the endothelial lining coming in intimate contact with syncytial membrane. The
rate of exchange is then greatly increased.
5. Functions of placenta
a. Exchange of gases, nutrients, metabolites between the maternal and fetal blood.
b. Protection: most foreign particulate matter such as bacteria is unable to pass
through the placental barrier. However, maternal antibodies may pass across
placenta and the fetus obtains passive immunity against measles, smallpox and
others. Some viruses and most drugs pass the placenta and may cause
c. Hormone production -- all of follows from syncytiotrophoblast cells
1). Human chorionic gonadotropin (HCG) has similar effect to that of LH. It is
detectable in the blood and urine as early as the 5th week and useful for early
diagnosis of pregnancy.
2). Human placental lactogen (HPL) is a GH-like hormone. It can stimulate the
growth of the breasts in preparation for lactation.
3). Progesterone and estrogen also secreted, to maintain pregnancy when the
corpus luteum degenerates.
Ⅶ. Twins -- 2 types of twins: dizygotic and monozygotic
A. Dizygotic twins Result from simultaneous fertilization of two different oocytes by two
1. Each embryo develops its own placenta, chorionic sac and amniotic cavity.
Sometimes the two placentas are so close that they fuse into one.
2. Two members may have same or different sex. The external and genetic features are
no more alike than other brothers or sisters.
B. Monozygotic twins result from a single fertilized ovum.
1. Two members have same sex, identical blood groups and genetic makeup, very
similar physical appearance.
2. They form at various stages of development:
a. Splitting at the cleavage stage causes two blastocysts implanting separately. Each
embryo has its own placenta, chorionic sac, and amniotic cavity.
b. Splitting at the early blastocyst stage causes two inner cell masses. Two embryos
have a common placenta and chorionic sac, but separate amniotic cavities. This
is the most case.
c. Splitting at the stage of bilaminar germ disc causing two primitive streaks results
in two embryos with a common placenta, chorionic sac and amniotic cavity. In
this case, conjoined twins may occur (monsters).
Chapter 21 DEVELOPMENT OF HEAD AND NECK
I. Development of Branchial Apparatus -- It consists of branchial arches, branchial grooves
(clefts), pharyngeal pouches, and branchial membranes.
A. Branchial arches appear on both lateral sides of the head in the 4th and 5th week. They
are 6 paired bars of mesenchymal tissue separated by 5 deep ectoderm invaginations
called branchial grooves (clefts).
B. Coinciding to the grooves, 5 pairs of outpocketings from the endodermal lining of the
pharynx develop as pharyngeal pouches. The grooves and pouches approach each
other forming branchial membranes.
C. The first pair of branchial arches contribute to the formation of the face. The 2nd, 3rd, 4th
and 6th pairs form the neck. The 5th pair degenerates.
II. Development of the Face (4th - 8th week)
A. Primordia: Five prominences around the stomodeum: single frontonasal
prominence, paired maxillary and mandibular prominences from upper and lower
branches of ventral ends of each 1st branchial arch.
1. The two mandibular prominences grow medially and fuse to form the lower jaw and
2. On each side of the lower part of the frontonasal prominence, a local thickening of the
ectoderm appears as nasal placode. Two fast-growing ridges, the lateral and
medial nasal prominences, surround the nasal placode, which is depressed as the
3. The maxillary prominences grow medially and compress the medial nasal
prominences toward the midline. Then the medial nasal prominences merge with
each other and with the maxillary prominences forming the middle and lateral
portions, respectively, of the upper jaw and lip.
4. The lateral nasal prominences fuse with the maxillary prominences forming the alae,
lateral wall of the nose and nasolacrimal duct.
5. The lateral parts of the maxillary and mandibular prominences merge to form the
cheeks and make the oral fissure smaller.
6. The stomodeum and nasal pits deepen and form oral and nasal cavities, respectively.
At first they are communicated and later separated by the palate.
III. Development of the Palate (5th - 12th week)
A. Primordia: A triangular median palatine process from the internal side of merged nasal
prominence, and two shelf-like, horizontal lateral palatine processes outgrowing from
the maxillary prominences.
B. The lateral palatine processes gradually grow toward each other and fuse, and also fuse
with the median palatine process forming the palate.
IV. Derivatives of Pharyngeal Pouches
A. The first pharyngeal pouch forms the tympanic cavity, pharyngotympanic tube and
medial side of the tympanic membrane. The oppositing first branchial groove forms
external auditory meatus and lateral side of the tympanic membrane.
B. The second pouch forms the tonsilar fossa and the surface epithelium of the palatine
C. The dorsal part of the third pouch forms the inferior parathyroids, while the ventral part
differentiates into the thymus, both migrating caudally.
D. The fourth pouch develops into the superior parathyroids.
E. The fifth pouch gives rise to ultimobranchial body, which is incorporated in the thyroid.
The neural crest cells migrate into it and form the parafollicular or C cells.
V. Congenital Maiformations
A. Cleft lip usually is division of the upper lip, unilateral or bilateral. It results from failure of
the maxillary prominence to fuse with the medial nasal prominence on the same side.
B. The oblique facial cleft, extending from the upper lip to the medial margin of the orbit,
results from failure of the maxillary prominence to fuse with the lateral nasal prominence
on the same side.
C. Cleft palate results from failure of the lateral palatine processes to fuse with each other
or with the median palatine process. The defect may be unilateral or bilateral, complete
or incomplete, with or without cleft lip.
Chapter 22 DEVELOPMENT OF DIGESTIVE AND RESPIRATORY SYSTEMS
I. Primordium -- The primitive gut
A. The endoderm gives rise to mucosal and glandular epithelia of the digestive and
respiratory systems, and the splanchnic mesoderm forms the connective tissue,
muscles and the outermost mesothelia.
B. Foregut derivatives: pharynx, esophagus, stomach, proximal part of duodenum, liver,
pancreas, lower respiratory tract and lungs.
C. Midgut derivatives: distal duodenum, jejunum and ileum, cecum and appendix,
ascending colon, right two-thirds of transverse colon.
D. Hindgut derivatives: left one-third of transverse colon, descending colon, sigmoid
colon, rectum, proximal anal canal, urogenital sinus.
II. Development of Midgut
A. The midgut elongates rapidly forming a midgut loop. The vitelline duct is at the apex of
B. The loop enters the extraembryonic coelom in the umbilical cord during the 6th week,
because of its rapid growth and expansion of the liver. At the same time the loop rotates
90° counterclockwise. The cranial limb of the loop forms intestinal coils and a cecal
swelling appears in the caudal limb. The vitelline duct is obliterated during these
C. At about the 10th week, the intestine begins to return to the abdomen, with the small
intestine going first and cecal swelling last. Meanwhile they undergo an additional 180°
D. At first the cecal swelling is located in the right upper abdomen. Then it descends into
the right iliac fossa and forms ascending colon, cecum and appendix.
III. Development of Hindgut
A. The dilated terminal part of the hindgut, the cloaca, receives the allantois ventrally. Its
endoderm makes contact with the surface ectoderm forming the cloacal membrane.
B. In the angle between the allantois and hindgut, a transverse ridge, the urorectal septum,
arises and grows downward, dividing the cloaca into the urogenital sinus and
anorectal canal, and then dividing the cloacal membrane into the urogenital
membrane and anal mambrane.
C. The mesenchymal proliferation around the anal membrane forms an ectodermal
depression, the anal pit. The anal membrane ruptures in the 8 week.
D. The anorectal canal develops into the rectum and the upper part of the anal canal. The
lower third of the anal canal, however, is of ectodermal origin.
IV. Development of Liver and Gallbladder
A. The liver primordium, the hepatic diverticulum, grows out from the ventral wall of the
caudal end of the foregut.
B. The liver diverticulum divides into a large cephalic and a small caudal limb.
C. The cephalic limb later forms cords of liver cells, intrahepatic biliary apparatus, and
hepatic duct. The caudal limb forms the gallbladder and cystic duct.
V. Development of Pancreas
A. The pancreas develops from a large dorsal and a small ventral pancreatic buds which
arise from the endoderm of the most caudal part of the foregut.
B. When the duodenum rotates to the right, the dorsal bud migrates to left and the ventral
bud migrates to right, dorsally and to left, then comes to lie immediately below and
behind the dorsal bud.
C. Later the two buds fuse. The ventral bud forms the lower part of the head of the
pancreas. The dorsal bud forms the other part of the gland.
D. The main pancreatic duct forms from the distal part of the dorsal pancreatic duct and the
entire ventral pancreatic duct. The proximal part of the dorsal pancreatic duct either is
obliterated or persists as the accessory pancreatic duct.
VI. Development of Lower Respiratory Tract and Lungs
A. During the 4th week, the laryngotracheal groove appears in the ventral wall of the
foregut. It deepens to form the laryngotracheal diverticulum, which grows caudally
and is separated from the esophagus by the esophagotracheal septum.
B. The distal end of the diverticulum divides to form right and left lung buds, which develop
into lungs, and the undivided proximal part forms the trachea. The opening of the
diverticulum forms the larynx.
VII. Congenital Malformation
A. Atresia and stenosis of gut may result from improper recanalization of gut lumen. The
esophagus, duodenum, common bile duct are most frequently involved.
B. Meckel's (ileal) diverticulum is caused by persistence of a small portion of the vitelline
duct forming an outpocketing of the ileum. It is located 40-60 cm from the ileocecal
C. Umbilical fistula results from persistence of the entire vitelline duct forming a direct
communication between the umbilicus and ileum. A fetal discharge may be found at the
D. Congenital umbilical hernia results form failure of intestines to return to abdomen or
incomplete closure of extraembryonic coelom in the umbilical cord, in which the
E. Imperforate anus is caused by failure of the anal membrane to perforate, or by failure of
the anal pit to develop.
F. Rectal atresia is caused by deviation of the urorectal septum in dorsal direction,
probably with some kind of the rectal fistula.
G. Annular pancreas results from migration of the two portions of ventral pancreatic bud in
opposite directions, and surrounds the duodenum. This may cause duodenal
H. Tracheoesophageal fistula results from hypoplasia of the tracheoesophageal septum
causing a fistula between the trachea and esophagus. This is usually accompanied by
the esophageal atresia.
Chapter 23 DEVELOPMENT OF URINARY SYSTEM
I. Development of Kidney and Ureter
A. The intermediate mesoderm detaches from the somite, and the cervical part forms the
nephrotomes and the caudal part forms the nephrogenic cords.
B. The nephrotomes grow into the pronephros, which consist of the pronephric tubules
and duct, but soon degenerate.
C. The mesonephros arises in the nephrogenic cord and contains the mesonephric
tubules and mesonephric duct. The mesonephros and the medial developing gonad
form the urogenital ridge. By the end of the 2nd month, the mesonephros has
disappeared, leaving a pair of mesonephric ducts, which open into the cloaca, and a
few mesonephric tubules.
D. The metanephros or permanent kidney appears from 2 sources in the 5th week: the
ureteric bud and metanephric blastema.
1. Ureteric buds grow out from the mesonephric ducts just before they enter the cloaca,
and penetrate the caudal nephrogenic cord and branch repeatedly. They form the
collecting tubules, calyces, renal pelvis, and ureters.
2. Metanephric blastema, induced by the ureteric buds, develops into the nephrons.
The proximal end of the tubule forms the Bowman's capsule around the glomerulus,
and the distal end forms an open connection with the collecting tubule.
3. The kidney ascends later from the pelvic region to the abdomen.
II. Formation of Bladder and Urethra
A. During the 4th to 7th weeks, the upper part of the urogenital sinus develops into the
urinary bladder. With the caudal mesonephric duct incorporated into the bladder, the
ureter then opens separately. The top of bladder is continuous with the allantois, which
is later obliterated.
B. The lower part of the urogenital sinus forms the urethra. The terminal part forms the
penile urethra in males and the vestibule in females.
III. Congenital Malformations
A. Polycystic kidney results from the abnormal development of the collecting system,
resulting in constricted or atretic tubules. Alternatively, it may be caused by failure of the
collecting tubules and nephrons to join. The kidney contains many cysts, and failure of
the renal function may be caused.
B. Horseshoe kidney develops when both kidneys fail to ascend, and their lower poles
fuse together. Pelvic kidney results from failure of one kidney to ascend and is still in
C. Urachal fistula is caused by persisting allantois. Urine may drain from the umbilicus.
Chapter 24 DEVELOPMENT OF GENITAL SYSTEM
I. Development of Gonads
A. Indifferent stage
1. The gonads are derived from three sources: the coelomic epithelium, the
underlying mesenchyme, and the primordial germ cells.
2. The gonadal ridges mediocaudal to the mesonephros are formed by proliferation of
the coelomic epithelium and condensation of the underlying mesenchyme. The
epithelial cells penetrate the mesenchyme forming the primitive sex cords.
3. The large primordial germ cells migrate from the yolk sac to the gonadal ridge and
surrounded by the primitive sex cords.
B. Development of the testis
1. If the embryo carries XY sex chromosomes, the gonadal ridge cells have the H-Y
antigen on their membrane. Under influence of the H-Y antigen, the primitive sex
cords continue to proliferate and penetrate deep into the medulla to give rise to the
seminiferous tubules containing Sertoli cells and spermatogonia.
2. The mesenchyme adjacent to the surface develops into a dense layer of fibrous
tissue, the tunica albuginea. Those located between the sex cords develop into the
Leydig cells which later produce androgens to influence sex differentiation of the
genital ducts and external genitalia.
C. Development of the ovary
1. In female embryos with an XX sex chromosome complex, the gonadal ridge cells
have no H-Y antigen and the primitive sex cords extend into the medulla and then
2. The secondary sex cords are formed from the coelomic epithelium and the
primordial germ cells incorporate in them.
3. The secondary sex cords break up into isolated cell clusters, in which the germ cells
develop into the oogonia and the surrounding epithelial cells form the follicular cells.
These are the primordial follicles.
4. The oogonia divide during fetal life becoming the primary oocyte, and no oogonia are
present in the ovary at birth.
D. Descent of the testis
1. The gubernaculum forms extending from the lower pole of the testis, passing
through the inguinal canal, and attaching to the genital swelling.
2. Because of the rapid body growth and gubernaculum shortening the testis descends
down and finally into the scrotum.
3. A sac of peritoneum, the vaginal process, extends into the scrotum following the
course of the gubernaculum and covers the testis, becoming the tunica vaginalis.
The proximal part of the vaginal process becomes obliterated at birth.
II. Development of Genital Duct
A. Indifferent stage
1. There are two pairs of ducts in both sexes: the mesonephric duct and the
2. The paramesonephric ducts develop on each side from invaginations of the
coelomic epithelium. Its cranial end opens into the body cavity, and the caudal ends
of the two sides come together in the midline and fuse to form the uterine canal.
3. The tip of the canal contacts with the dorsal wall of the urogenital sinus, where it
causes a small swelling, the sinus tubercle.
B. Development of the male genital duct
1. The mesonephric duct develops, under the influence of androgens, into the ductus
epididymis, ductus deferens, ejaculatory duct and seminal gland. The mesonephric
tubules form the efferent ductules of the testis.
2. The paramesonephric duct regresses because of anti-Mullerian duct hormone
produced by the Sertoli cells.
C. Development of the female genital duct
1. The paramesonephric duct develops into the uterine tube. The uterine canal forms
the uterus and the upper one-third of the vagina.
2. The sinus tubercle proliferates to form the vaginal plate, which later is canalized,
forming the lower two-thirds of the vagina.
3. The mesonephric duct degenerates.
III. Development of External Genitalia
A. Indifferent stage: The mesenchyme around the urogenital membrane forms laterally a
pair of the urogenital folds, and cranially the genital tubercle. Meanwhile another pair
of elevations, the labioscrotal swellings, on each dide of the urogenital folds are
formed. Between the urogenital folds is the urethral groove.
B. Differentiation of external genitalia:
Male (androgens) Female (no androgen)
Genital tubercle phallus clitoris
Urogenital folds lateral wall of urethra labia minora
Labioscrotal swellings scrotum labia majora
Urethral groove penile urethra vestibule
Ⅳ. Congenital Malformations
A. Cryptorchism is failure of one or both testes to descend into the scrotum, seeming to be
due to abnormal androgen production. The testes may remain in the abdomen or in the
B. Congenital inguinal hernia results from failure of the vaginal process to close normally,
and intestinal loops may descend into the scrotum.
C. Vaginal atresia is caused by failure of the vaginal plate to form or to be canalized.
1. True hermaphrodites have the gonads and external genitalia of both sexes. They
are rarely observed.
2. Pseudohermaphrodites have either testes (male) or ovaries (female) and possess
the external genitalia resembling the opposite sex. They are caused by inadequate
(male) and excessive (female) androgen production, respectively.
E. Testicular feminization syndrome results from devoid of the androgen receptors in the
tissues of the external genitalia. The patients have a 44+XY chromosome complement
and the testes frequently found in the inguinal region, but with no spermatogenesis. The
external genitalia develop and differentiate as in the female but the uterine tubes and
uterus are absent.
F. Hypospadias has abnormal openings of the urethra along the inferior aspect of the
penis, resulting from incomplete fusion of the urogenital folds.
Chapter 25 DEVELOPMENT OF CARDIOVASCULAR SYSTEM
I. Development of Early Blood Vessels
A. During the 3rd week, isolated cell clusters (blood islands) first appear in the mesoderm
of the wall of yolk sac. The peripheral cells flatten and give rise to endothelia forming
vessels, while the centrally located cells develop into primitive blood cells.
B. Then blood vessels form in similar manner in the chorion, body stalk, and in the body of
the embryo. These vessels connect to each other and form 3 separate circulations:
vitelline, chorionic, and intraembryonic.
II. Development of Primitive Heart Tube
A. The mesoderm cranial to the oropharyngeal membrane differentiates into the
cardiogenic area with the pericardial coelom over it. The cardiogenic area first forms
two lateral cardiogenic plates, which then canalize to form the heart tubes.
B. With the lateral fold, two heart tubes fuse into a single endocardial heart tube. With the
head fold, the pericardial coelom rotates ventrally to the heart tube and they both
become located caudally to the oropharyngeal membrane.
C. The mesoderm adjacent to the heart tube forms myoepicardial mentle, which is
separated from the endocardial heart tube by the cardiac jelly. Finally the myoepicardial
mentle forms the myocardium and the epicardium, the endothelial tube gives rise to the
endocardium, and the cardiac jelly forms the subendocardial tissue.
III. Formation of Heart Loop
A. The heart tube elongates and is subdivided into four dilatations: bulbus cordis,
ventricle, atrium and sinus venosus. The distal part of the bulbus cordis is called the
B. The bulboventricular portion grows much more rapidly than other parts of the tube and
the pericardial coelom. The heart tube then bends forming a bulboventricular loop.
C. The cephalic portion of the loop bends ventrally, caudally and slightly to the right. The
atrium shifts dorsocranially and bulges laterally on each side of the bulbus.
D. The atrioventricular sulcus remains narrow forming the atrioventricular canal internally.
IV. Partitioning of the Heart Chambers (4th - 8th weeks)
A. Division of atrioventricular canal
1. Two endocardial cushions develop from subendocardial tissue in the dorsal and
ventral walls of the canal.
2. The cushions grow toward each other and fuse, dividing the canal into right and left
B. Partitioning of the primitive atrium
1. A thin sickle-shaped crest, the septum primum, grows from the roof of the atrium
toward endocardial cushions, leaving an opening between its lower rim and
endocardial cushions, called the foramen primum.
2. Before the ostium primum closing, the upper part of the septum primum becomes
perforated forming the foramen secundum.
3. A thick membrane called the septum secundum appears on the right of the septum
primum, and extends downward to cover the foramen secundum, but leaving an oval
opening, the foramen ovale. The septum primum serves as the valve of the oval
4. Blood can only flows from the right to left atrium through the oval foramen. After birth,
the valve is pressed against the septum secundum by increased pressure in the left
atrium, thus obliterating the oval foramen and separating the right and left atria.
C. Partitioning of the primitive ventricle
1. The ventricle wall at the apical part grows to form the muscular interventricular
septum, but an interventricular foramen remains between the top edge of the
septum and endocardial cushion.
2. The interventricular foramen is later closed by the membranous interventricular
septum, which is derived from the endocardial cushion, right and left bulbar
D. Division of truncus and bulbus
1. Two spiral truncal ridges grow from the inner walls of the truncus, and bulbar ridges
also form in the bulbus and become continuous with the truncal ridges.
2. The opposing ridges twist around each other and fuse to form a spiral
aorticopulmonary septum. It divides the bulbus and truncus into two channels: the
aorta connecting to the left ventricle and the pulmonary trunk connecting to the right
3. The proximal part of the bulbus incorporates into the right ventricle. The midportion,
the conus cordis forms the outflow tracts of both ventricles.
V. Circulation before and after Birth
A. Circulation before birth
B. Changes after birth
1. Closure of the umbilical arteries → lateral umbilical ligaments
2. Closure of the umbilical vein → ligamentum teres hepatis
3. Closure of the ductus venosus → venous ligament
4. Closure of the ductus arteriosus → arterial ligament
5. Closure of the oval foramen → oval fossa
VI. Congenital Malformations
A. Atrial septal defect is most commonly caused by excessive resorption of the septum
primum or by inadequate development of the septum secundum.
B. Ventricular septal defect is often caused by defect of the membranous septum,
isolated or associated with other abnormalities.
C. Tetralogy of Fallot, caused by an unequal division of the conus cordis, consists of 4
defects: pulmonary stenosis, overriding aorta, ventricular septal defect, and
hypertrophy of right ventricle. This is the most important type of malformations
D. Transposition of the great vessels results from the truncoconal septum failing to follow
its normal spiral course and descending straight downward. The aorta originates from
the right ventricle and the pulmonary artery from the left.
E. Patent ductus arteriosus is the condition in which the ductus arteriosus fails to close.