Developmental Anatomy

Developmental Anatomy
Lecture Syllabus
Department of Histology & Embryology
Peking Union Medical Collage
2. EARLY DEVELOPMENT OF HUMAN EMBRYO.......................2
3. HUMAN BIRTH DEFECTS............................................................ 11
4. DEVELOPMENT OF HEAD AND NECK ....................................14
7. DEVELOPMENT OF DIGESTIVE SYSTEMS............................21
8. DEVELOPMENT OF URIGENITAL SYSTEM ...........................25
10. DEVELOPMENT OF THE NERVOUS SYSTEM .......................34
I. Definition:
1. Embryology: developmental anatomy, the study of the formation and development
of embryos.
2. Human embryology is a science that studies the normal development as well as
the birth defects of a human being in the maternal uterus.
II. The History of Embryology
1. Early History
2. Renaissance History
3. Experimental Embryology
4. Progress of modern embryology: test tube babies & somatic cell cloned animals
III. The main branches of Embryology
1. Descriptive Embryology
2. Comparative Embryology
3. Experimental Embryology
4. Chemical Embryology
5. Molecular Embryology
6. Reproductive Engineering
7. Teratology
IV. Why a medical student should study Embryology?
V. Introduction of the development of an embryo
prenatal periods
38 weeks
fertilization age & gestational age
Three developmental periods are divided:
1. Preembryonic period (0-2 weeks): fertilization to formation of the bilaminar germ
2. Embryonic period (3-8 weeks): trilaminar embryonic disc formation &
3. Fetal period (9-38 weeks): growth of the organ systems.
I. Gametogenesis
A process of formation and maturation of the gamete (spermatozoa in male and ova
in female), including chromosomal and morphological changes.
1. Migration of primordal germ cells (PGCs)
2. Spermatogenesis
3. Oogenesis
II. Fertilization to Implantation (1st Week of Development)
1. Fertilization: A sperm + an oocyte → zygote
1) before fertilization
(1) male gametes (spermatozoa)
a. number and viability:
b. transport of ejaculated spermatozoa
capacitation of spermatozoa:
 site: in the female genital tract
 method: removal of a glycoprotein coat from the plasma membrane of the
acrosomal region
 result: obtaining capacity of fertilizing an egg
(2) female gamete (oocyte)
a. number
b. transport of ovulated secondary oocyte
(3) two gametes meeting
a. time:
spermatozoa: < 48 hours after ejaculation
oocyte: 12 - 24 hours after ovulation
b. site: ampulla of oviduct
2) process of fertilization
(1) acrosome reaction: release of enzymes from acrosome
(2) zona reaction:
zona becomes impenetrable to other sperm (monospermy), through
lysosomal enzyme release from cortical granules of oocyte to change
structure and composition of the zona.
(3) process of fertilization:
penetration, recognition & fusion
ZP3 is responsible for species-specific fertilization
3) after fertilization
(1) oocyte finishes 2nd meiosis
(2) formation and merge of male and female pronuclei → cleavage
4) Result of fertilization
(1) restoration of diploid number of chromosome
(2) species variation
(3) primary sex determination: Y+X = male, X+X = female
(4) activation of egg metabolism and initiation of cleavage
2. Cleavage and blastocyst formation
mitotic division
blastomeres → morula → blastocyst
inner cell mass
blastocyst cavity
embryonic stem cell (ES cell)
hatching of blastocyst: ~ day 5- 6
3. Implantation: a process of the blastocyst embedding into the endometrium
1) Time: Day 5 - 6 to Day 11 - 12
2) Site: posterior or anterior wall of uterine body
3) Process:
adhesion, expansion, dissolution, invasion, differentiation, repair
4) The main changes during implantation (differentiation)
(1) Formation of bilaminar embryonic disc
inner cell mass →
embryonic disc
(2) Decidual reaction
decidua basalis
decidua capsularis → degeneration
decidua parietalis
(3) Formation of the early fetal membranes
exocoelomic membrane (& cavity)
extraembryonic endoderm
of primary yolk sac
primitive streak
secondary yolk sac
extraembryonic somatic connecting stalk
umbilical cord
chorionic cavity
chorionic sac
5) Requirements of implantation
(1) Zona pellucida disappears in time
(2) Normal development and transport of the young embryo
(3) Endometrium in secretory phase
(4) Normal endocrine regulation
6) Abnormal implantation
(1) Ectopic pregnancy
(2) Placenta previa
7) Contraception
(1) Intervening the processes of gamete production: contraceptive pills
(2) Intervening the processes of fertilization
a. condom & diaphragm
b. terilization: vasectomy & tubal ligation
(3) Intervening the processes of implantation
a. intrauterine devices (IUD)
b. post-coital contraception
4. Human assistant reproductive technology
1) Artificial insemination
2) In vitro fertilization-embryo transfer, IVF-ET
2nd week -- “ the period of twos”
two embryonic layer: epiblast & hypoblast
two trophblast layers: cytotrophoblast & syncytiotrophoblast
two cavities: amniotic cavity & yolk sac
III. Formation of three germ layers (3rd Week)
1. Gastrulation: Gastrula
epiblastic cells proliferation & migration
bilaminar embryonic disc
trilaminar embryonic disc
1) Formation of the primitive streak
primitive streak & primitive groove
epiblastic cells →
primitive knot & primitive pit
2) Formation of intraembryonic endoderm and mesoderm
3) Formation of trilaminar germ disc
All 3 germ layers are derived from the epiblast.
There are two areas that have no mesoderm:
prechordal plate → oropharyngeal membrane
cloacal membrane
4) Formation of the notochord
(1) Process:
primitive node & primitive pit (median cranial migration) →
notochordal (head) process → notochordal canal (neurenteric canal)
→ notochordal plate → notochord
(2) Function: primary inductor, induction of neural plate formation
5) Fate of the notochord & primitive streak
(1) The fate of notochord: degeneration, forming the nucleus pulposus of
intervertebral disc
(2) The fate of primitive streak: degeneration
(3) Teratoma: oropharyngeal & sacrococcygeal teratoma
2. Neurulation: the process of neural tube formation
1) Formation of the neural tube
ectoderm cells (overnotochord)
neural plate
neural groove & neural fold → neural tube
The neural tube is the primordium of the central nervous system (CNS).
2) Formation of the neural crest
The neural crest is the primordium of the peripheral nervous system (PNS).
3rd week -- “period of threes”
three germ layers: ectoderm, mesoderm & endoderm
three important structure: primitive streak, notochord & neural tube
IV. Differentiation of Germ Layers and Establishment of Body Form (3 rd to 8th
1. Differentiation of ectoderm
1) Neural ectoderm
(1) neural tube → CNS
 rostral (anterior) neuropore: closed by 25-26 days
 caudal (posterior) neuropore: closed by 27-28 days
(2) neural crest → PNS, the chromaffin cells of the adrenal medulla,
parafollicular cells of the thyroid, melanocytes, and part
of mesenchyme in the pharyngeal apparatus.
(3) anencephaly & myeloschisis (spina bifida)
2) Surface ectoderm
(1) epidermis and its appendages
(2) adenohypophysis
(3) sensory epithelium of the ear, nose, tongue
(4) lens of the eye
(5) enamel of the teeth
2. Differentiation of mesoderm
paraxial mesoderm → somites
mesoderm →
intermediate mesoderm
lateral mesoderm
1) Derivatives of the somite
somites ( 3 pairs/day, 42 - 44 pairs in total )
sclerotome → paraxial skeleton
somite →
myotome → muscles
dermatome → dermis
2) Derivatives of the intermediate mesoderm
the primordium of the urogenital system forming the kidneys and gonads, etc.
3) Derivatives of the lateral mesoderm
somatic mesoderm → bones, muscles and C.T. and mesothelium
lining inner surface of body wall
mesoderm→ intraembryonic coelom
splanchnic mesoderm → muscles and C.T. of viscera, and
mesothelium covering them
3. Folding of the embryo
the embryonic disc
rapid growth of somites
rapid growth of CNS
head and tail folds
lateral fold
cylindrical embryo
4. Formation of primitive gut
york sac → primitive gut (foregut, midgut, hindgut) → primordium of digestive
and respiratory systems
5. Differentiation of endoderm
endoderm → epithelial of digestive & respiratory tract, and bladder, urethra;
parenchyma of liver, pancreas, tonsil, thyroid, parathyroids, thymus;
epithelium of tympanic cavity and Eustachian tube.
V. Fetal membranes and placenta
fetal membranes including chorion, amnion, yolk sac, umbilical cord & allantois
nutrition, protection, respiration, excretion, endocrine &
immunological barrier preventing rejection of fetus as an allograft
1. Chorion
extraembryonic somatic mesoderm + cytotrophobalst + syncytiotrophoblast
1) Chorionic villi
(1) development of villi:
primary stem villi: cytotrophoblast + syncytiotrophoblast
secondary stem villi: with a core of loose C.T.
tertiary stem villi: with blood vessels in the loose C.T. core
(2) cytotrophoblastic shell (细胞滋养层壳)
stem villi (anchoring villi) , branch villi (terminal villi)
(3) villous chorion (丛密绒毛膜 chorion frondosum) & smooth chorion (平滑绒
毛膜 chorion leave)
2) intervillous space
isolated lacunae in the syncytiotrophoblast → fused to lacunar networks →
intervillous space
chorionic plate, primitive uteroplacental circulation
3) abnormal growth of the trophoblast:
Hydatidiform Moles (葡萄胎), Choriocarcinomas (绒毛膜癌)
2. Amnion & Amniotic fluid
1) amniotic sac, amniotic cavity & amniochorionic membrane
2) amniotic fluid
(1) origin: amniotic cells, maternal & fetal blood, tissue fluid and fetal urine etc.
(2) circulation and exchange:
a. by mother
b. by fetus
(3) composition:
(4) volume: 10w: 30ml, 20w: 350ml, 37w: 700-1000ml
 < 400ml → oligohydramnios
 > 2000ml → polyhydramnios
 amnionic band
(5) significance:
a. protection
b. prevent adherence of the amnion to the embryo and fetus
c. controlling the embryos temperature
d. enabling the embryo to move freely and grow
e. maintaining homeostasis of fluid and electrolytes
f. permitting normal fetal lung development
g. dilating and washing the cervix during the labor
h. prenatal diagnosis
-Fetoprotein (-AFP)
premature rupture of the amnion
3. Yolk sac
1) significance:
(1) transfer of nutrients (2-3w)
(2) blood development (mesoderm, 3-5w)
(3) primitive gut (4w)
(4) primordial germ cells (endoderm, 3w)
2) fate:
yolk stalk → Meckels diverticulum(憩室)
4. Allantois
1) origin: finger-like diverticulum from the caudal wall of the yolk sac that extends
into the connecting stalk
2) significance:
(1) blood formation: 3-5w
(2) umbilical vein and arteries
(3) a part of urinary bladder
3) fate:
urachus (脐尿管) → median umbilical ligament
5. Umbilical cord
mucous connective tissue covered by amnion, including two arteries, one vein,
atrestic allantois and atrestic yolk stalk
1-2cm in diameter, 30-90cm in length (average 55cm)
false knots and true knots
6. Placenta
1) Composes and Shape:
(1) composes: fetomaternal organ
the fetal component: the villous chorion
the maternal component: the decidua basalis
(2) shape: discoid, 15-20cm in the diameter, 2-3cm thickness, 500-600gm weight
a. maternal surface of the placenta: rough
cotyledon(胎盘小叶), groove (placenta septa)
b. fetal surface of the placenta: smooth
amnion, umbilical cord, and radiating chorionic vessels
2) The fetomaternal junction
cytotrophoblastic shell, stem villi (anchoring villi)
placenta accrete (植入胎盘), placenta increta, placenta percreta (穿透性胎盘)
3) Placental circulation
fetal placental circulation
( within the villus )
umbilical A. →→ arterio-capillary-venous system →→ umbilical V.
spiral A. → intervillous space → endometrial V.
maternal placental circulation
intrauterine growth retardation (IUGR)
4) Placental membrane or Placental barrier
(1) < 20w
a. syncytiotrophoblast
b. cytotrophoblast and basal lamina
c. connective tissue in the chorionic villi
e. endothelium and basal lamina of the fetal capillary
(2) > 20w
a. syncytiotrophoblast and basal lamina
b. endothelium and basal lamina
5) Functions of placenta
(1) metabolism
(2) transport of substances
nutrients, gases, waste products, drugs, hormones, Ag, Ab, etc
(3) endocrine secretion
a. protein hormones:
 human chorionic gonadotropin (hCG)
 human chorionic somatomammotropin (hCS) or human placental lactogen
 human chorionic thyrotropin (hCT)
 human chorionic corticotropin (hCACTH)
b. steriod hormones:
 progesterone
 estrogens
VI. Parturition (分娩)
VII. Twins and other multiple pregnancies
1. Twins
1) dizygotic twins (双卵双胎)
 same or different sex
 the external and genetic features are no more alike than other brothers or sisters.
 separate placenta, chorionic sac and amniotic cavity
 sometimes two placentas fuse into one
2) monozygotic twins (单卵双胎)
 same sex, very similar physical appearance
 identical blood groups and genetic makeup
(1) separation of the embryonic blastomere (35%)
 separate placenta, chorionic sac and amniotic cavity
 sometimes two placentas fuse into one
(2) separation of the inner cell mass (65%)
 common placenta and chorionic sac
 separate amniotic cavity
 sometimes having placental vascular anastomoses
Twin transfusion syndrome
(3) division of the embryonic disc
a. separate twins
b. conjoined Twins (联胎)
c. parasitic twin (寄生胎)
2. Other multiple pregnancies
1) Triplets
2) Quadruplets
I. Introduction
1. What’s birth defect?
Developmental disorders present at birth (congenital malformations)
Structural, functional, metabolic, behavioral or hereditary
2. Teratology
3. Incidence of birth defect
Leading cause of infant mortality
Major anomalies 2-3%; Minor anomalies 15%
II. Causes of birth defects
1. Genetic factors
1) Numerical abnormalities of chromosomes
(1) Autosomes
a. Trisomy 21 (Down’s syndrome)
Incidents -- maternal age < 25yrs: 1/2000; maternal age > 40yrs: 1/100
With heart defect and simian crease
b. Trisomy 18 (Edwards syndrome)
c. Trisomy 13 (Patau syndrome)
(2) Sex chromosomes
a. Turner’s syndrome (XO):
Short stature, webbed neck, lymphedema, no ovary, mental retardation
b. Klinefelter’s syndrome (XXY)
Testicular atrophy, sterility, gynecomastia
c. Tetrasomy and pentasomy
(3) Triploidy and Teraploidy
2) Structural abnormalities of chromosomes (break, deletion, insertion, etc.)
(1) Cri du chat syndrome
Loss or misplacement of genetic material from chromosome 5
(2) Prader-Willi syndrome and Angelman syndrome
Deletion of q11-13 on parental ch15
3) Mutations of genes: a few malformations
(1) Phenylketonuria (PKU)
(2) Achondroplasia
(3) Fragile X syndrome
2. Environmental factors (teratogens)
A teratogen is any agent that can produce a congenital anomaly or raise the
incidence of an anomaly in the population.
• The embryonic period (weeks 3-8) is highest susceptible because of intensive
• Different organs have different susceptible period corresponding to their own
critical development stage
• Different teratogens also have different susceptible period.
1) Drugs
(1) Social drugs
a. Cigarette: nicotine causes hypoxia  intrauterine growth retardation (IUGR)
b. Alcohol: fetal alcohol syndrome (FAS):
Flat midface, indistinct philtrum, thin upper lip, mental retardation, etc
(2) Oral contraceptive and diethylstilbestrol (DES):
Vertebral, Anal, Cardiac, Trachea, Esophageal, Renal, Limb
(3) Antibiotics
a. Tetracycline: bones and teeth defects
b. Streptomycin derivatives: deafness
(4) Anticoagulants: warfarin,
6-12w: hypoplasia of the nasal cartilage, stippled epiphyses, CNS defects
Later: mental retardation, optic atrophy, microcephaly
(5) Anticonvulsants
a. Trimethadione: fetal trimetadione syndrome
b. Phenytoin: Fetal hydantoin syndrome
(6) Antineoplastic agents
aminopterin (Folic acid antagonist): CNS & skeletal defect
(7) Isotretinoin
(8) Thalidomide (24-36d)
meromelia, ear & heart defects, hemangioma, urinary & alimentary anomalies
2) Environmental chemicals
(1) Methylmercury: Minamata disease (水俣病)→ brain damage
(2) Lead: IUGR, fuctional deficits
(3) Polychlorinated biphenyls (PCBs): IUGR, skin discoloration
3) Infectious agents
(1) Rubella (4-5w)
Congenital rubella syndrome (CRS): cataract, cardiac defects, deafness
(2) Cytomegalovirus (CMV)
Early: spontaneous abortion
Later: IUGR, eye defects, microcephaly, cerebral palsy, hepatosplenomegaly
(3) Herpes simplex virus (HSV)
(4) Varicella
(5) Human immunodeficiency virus (HIV)
(6) Toxoplasmosis
Early: fetal death
Later: mental deficiency, microcephaly, microphthalmia, hydrocephaly
(7) Congenital syphilis
4) Radiation
(1) Atomic bomb: CNS malformations
(2) Electromagnetic fields
(3) Ultrasonic waves
5) Maternal factors
(1) Diabetes mellitus
(2) PKU
6) Mechanical factors
(1) Oligohydramnios
(2) Amniotic bands
Congenital dislocation of the hip and clubfoot
3. Multifactorial inheritance
III. Diagnosis and treatment
1. Education
1) Away from deleterious factors
2) Folate supplementation
2. Prenatal Diagnosis
1) Maternal serum screening: CMV, AFP….
2) Ultrasound
3) Amniocentesis
4) Chorionic villus sampling
3. Treatment
I. Origin and development of the pharyngeal (branchial) apparatus
1. Origin of the Pharyngeal Apparatus---from neural crest
Appear in 4-5th week, disappear by the end of 6th week
The pharyngeal apparatus include:
1) Pharyngeal arches
2) Pharyngeal grooves (clefts)
3) Pharyngeal membranes
4) Pharyngeal pouches
2. Development of the Pharyngeal Apparatus
1) Fate of pharyngeal arches
(1) 1st arch
mandibular process (prominence)
maxillary process (prominence)
(2) 2nd arch (hyoid arch)
a. Derivatives of the pharyngeal arch cartilages
b. Derivatives of the pharyngeal arch muscles
1st arch → mastication, 2nd arch → facial expression
c. The cranial nerves supplying the pharyngeal arches
2) Fate of pharyngeal grooves
(1) 1st groove
the external auditory meatus
(2) 2nd, 3rd, 4th groove
cervical sinus
Congenital anomalies:
a. Branchial cysts & sinuses
failure of closure of cervical sinus (cyst); may connect to surface or pharynx
(sinus); along anterior border of sternocleidomastoid muscle
b. Branchial fistulas
3) Fate of pharyngeal membranes
(1) 1st membrane
tympanic membrane
(2) 2nd, 3rd, 4th membrane
4) Fate of pharyngeal pouches
(1) 1st pouch → tubotympanic recess distal portion →primitive tympanic cavity
proximal portion → auditory tube
(2) 2nd pouch → palatine tonsil
(3) 3rd pouch
dorsal portion
inferior parathyroid gland
ventral portion
(4) 4th pouch
dorsal portion
superior parathyroid gland
ventral portion
ultimobranchial body
(5) 5th pouch → ultimobranchial body
parafollicular cells
Congenital anomalies: Ectopic parathyroid gland
II. Development of the face (4-8W)
1. Primordia
5 prominences around stomodeum
Single frontonasal prominence
Paired maxillaryprominences
Paired mandibular prominences
2. Development
1) Mandibular prominences
lower jaw and lip
2) Maxillary prominence
cheek and lateral upper lip
3) Frontonasal prominence upper part → forehead
medial nasal prominence
lower part → nasal placode nasal pits → nasal cavity
lateral nasal prominence
medial nasal prominences
nasal septum & apex
maxillary prominence
lateral nasal prominence → alae, lateral wall of nose
nasolacrimal groove → nasolacrimal duct
4) Stomodeum → oral cavity
Nasal sac → nasal cavity
III. Development of the palate (5-12W)
medial nasal prominences → nasal septum
maxillary prominence
intermaxillary segment
1 median palatine process
(primary palate)
(anterior to the incisive fossa)
2 lateral palatine processes
(secondary palate)
(posterior to the incisive fossa)
Congenital anomalies: Facial clefts (clefts lip and (or) palate)
1. Cleft lip: division of upper lip, unilateral or bilateral
Failure of maxillary prominence to fuse with medial nasal prominence
2. Oblique facial cleft:
division extending from the upper lip to medial margin of orbit
Failure of maxillary prominence to fuse with lateral nasal prominence
3. Cleft palate: uni- or bilateral, complete or incomplete, with or without cleft lip
Failure of lateral palatine process to fuse with each other or with median
palatine process
IV. Development of the tongue (~ 4W)
2 distal tongue bud(lateral lingual swelling)
median sulcus
1st arch
oral part (anterior to foramen cecum)
1 median tongue bud (tuberculum impar)
2nd arch
pharyngeal par (posterior to foramen cecum)
3rd & 4th arch
hypobranchial eminence
Congenital anomalies: Ankyloglossia (tongue-tie) and macroglossia
V. Development of the thyroid gland (24d-7w)
Foramen cecum
median endodemal thickening
Thyroid diverticulum
thyroglossal duct
Thyroid gland
Congenital anomalies:
1. Thyroglossal duct cysts and sinuses: median location
2. Ectopic thyroid gland
I. Early Development of the Intraembryonic Coelom
1. coelomic spaces
3w end, small, isolated coelomic spaces in the lateral mesoderm & cardiogenic
2. horseshoe-shaped intraembryonic coelom
4w beginning, horseshoe-shaped intraembryonic coelom, communicated with
extraembryonic coelom
somatic mesoderm
lateral mesoderm
splanchnic mesoderm
3. partitioning of the intraembryonic coelom
4w, embryonic folding
pericardial cavity
intraembryonic coelom pericardioperitoneal canals(心包腔腹膜腔间管,胸膜管)
peritoneal cavity
10w, peritoneal cavity separated from extraembryonic coelom
II. Partitioning of the Coelom
due to growth of the bronchial buds
1. the pleuropericardial membranes (心胸隔膜)
1) 5w, the cranial ridges:the pleuropericardial fold
→ the pleuropericardial membranes (contain the common cardinal vein)
2) 7w, fuse with mesoderm ventral to the esophagus
the right opening closed earlier than the left one
3) primordial pleural cavity expand ventrally
thoracic wall
body wall
fibrous pericardium(心包纤维层)
2. the pleuroperitoneal membranes(胸腹隔膜)
1) 5w, the caudal ridges: the pleuroperitoneal folds
→ the pleuroperitoneal membranes
2) 6w end, fuse with the septum transversum & the dorsal mesentery of esophagus
right opening closed earlier than the left
III. Development of the Diaphragm
1. components
septum transversum → the central tendon
pleuroperitoneal membranes → small portion
dorsal mesentery of esophagus → the crura
lateral body walls (9-12w) → peripheral portion
2. position changes and innervation of the diaphragm
4 w 3-5 cervical somites
(5w, myoblasts migration, phrenic nerves)
6w thoracic somites
8w first lumbar vertebra
IV. Congenital Anomalies
1. congenital diaphragmatic hernia (CDH)
defective formation &/or fusion of the pleuroperitoneal membrane with other parts
2. eventration of the diaphragm (膈膨升)
failure of muscular tissue extend into the pleuroperitoneal membrane
I. Development of the Trachea, Bronchi and Lungs
1. respiratory primordium
laryngotracheal groove
4w end laryngotracheal diverticulum
tracheoesophageal →
laryngotracheal tube
(primordium of the lower R.S. )
lung bud
2. histology
endoderm: epithelium and glands
splanchnic mesoderm: CT, cartilage, smooth muscle, etc.
3. development of the trachea
4. development of the bronchi and lungs
lung bud (4w end) → bronchial buds → main bronchus (5w) → secondary
bronchi → segmental bronchi (7w) → 17 orders of branches, respiratory
bronchioles developed(24w) → additional 7 orders (after birth)
II. Maturation of the Lungs
1. the pseudoglandular period (5-17 w) (假腺期)
the bronchi and terminal bronchioles formed
columnar epithelium
2. the canalicular period (16-25 w) (小管期)
lumina of bronchi & bronchioles enlarged
respiratory bronchioles (24w) developed
terminal sacs (primordial alveoli) appeared
lung tissue highly vascularized
3. the terminal sac period (24 w - birth) (终末囊泡期)
terminal sacs developed
epithelium: cuboidal → squamous
type I alveolar cells
type II alveolar cell: pulmonary surfactant
alveolocapillary membrane(肺毛细血管膜)established
4. the alveolar period (late fetal period – childhood) (肺泡期)
respiratory bronchioles & primitive alveoli increase
primordial alveoli → mature alveoli
• lung fluid
III. Congenital Anomalies
1. tracheoesophageal fistula
defective tracheoesophageal septum
2. respiratory distress syndrome (RDS, hyaline membrane disease)
surfactant deficiency
3. lung hypoplasia
oligohydramnios, CDH, etc.
I. Primitive Gut Tube
1. formation
4w, embryonic folding
dorsal part of the yolk sac + splanchnic mesoderm → primordial gut
2. histology
endoderm → most of the epithelium & glands
splanchnic mesenchyme → CT, muscular, & other layers
ectoderm of stomodeum & proctodeum
oropharyngeal membrane, cloacal membrane
3. recanalization
epithelium: proliferated (4-5w) → degenerated
lumen : obliterated → vacuolation → recanalized (8w)
congenital anomalies:
4. mesenteries
5. blood supply
celiac A.
superior mesenteric A.
inferior mesenteric A.
II. The Foregut
1. esophagus
tracheoesophageal septum
congenital anomalies:
• esophageal atresia/ stenosis
2. stomach
1) stomach
growth: morphogenesis: fusiform(4w middle) → pouchlike
rotation: (6-12w):
around its longitudinal axis, 90, clockwise
around the ventrodorsal axis, 90, clockwise
2) mesogastrium
cavity in dorsal mesogastrium → the omental bursa
superior part: infracardiac bursa(心下囊) + superior recess
inferior recess, omental bursa
congenital anomalies:
• congenital hypertrophic pyloric stenosis
3. duodenum
derived from foregut & midgut
growth: C-shaped loop,
rotation: → retroperitoneal; → right
congenital anomalies:
• duodenal stenosis / atresia
4. liver & biliary apparatus:
4w early,hepatic diverticulum extended into the septum transversum
cranial part: liver primordium
caudal part: cystic primordium
1) liver primordium
endoderm: hepatic cords, intrahepatic portion of biliary apparatus
mesenchyme in septum transversum → C.T.
6w hematopoiesis ; 12 w bile begin formation
2) the ventral mesentery
inferior part of the septum transversum → the ventral mesentery
a. falciform ligament
b. the lesser omentum: hepatogastric ligament + hepatoduodenal ligament
c. visceral peritoneum of the liver
bare area
3) cystic primordium
→ gallbladder, cystic duct
4) common bile duct
the connecting stalk → common bile duct
the entrance: ventral → dorsal aspect of the duodenum
5) congenital anomalies:
• extrahepatic biliary atresia
5. pancreas
dorsal pancreatic bud
rotation & fusion → pancreas
ventral pancreatic bud
main pancreatic duct : ventral pancreatic duct + dorsal pancreatic duct
accessory pancreatic duct
congenital anomalies:
• anular pancreas
III. The Midgut
1. rotation of the midgut loop
blood supply: superior mesenteric artery
yolk stalk → midgut loop → cranial limb + caudal limb
6-10w, 270, counterclockwise, around the superior mesenteric A. (axis)
1) physiological umbilical herniation formation
6w, midgut loop: → umbilical coelom
rotation: around the superior mesenteric A, 90  counterclockwise
cranial limb: small intestinal loops
caudal limb: cecal diverticulum
yolk stalk obliterated
2) return of the midgut to abdomen 10w
first: the small intestine returns, posterior to the superior mesenteric A. , occupy
the central part of the abdomen
then: the large intestines returns, undergoes further 180 counterclockwise
last: the cecum, below liver → the right iliac fossa
ascending colon appears
3) fixation of the intestines
retroperitoneal: duodenum, pancreas, the ascending colon
mesentery: duodenojejunal junction to ileocecal junction
2. cecum & appendix
6w,cecal diverticulum
appendix: a small diverticulum of the cecum
3. congenital anomalies:
• congenital omphalocele(脐膨出)
• umbilical hernia(脐疝)
• gastroschisis (腹裂)
• anomalies of midgut rotation
• ileal (Meckel) diverticulum & other yolk stalk remnants
IV. The Hindgut
1. fixation of the hindgut
retroperitoneal: descending colon
2. the cloaca
1) partitioning of the cloaca (4-6w)
urorectal septum: a forklike extensions
ventral: urogenital sinus
dorsal: rectum & cranial part of the anal canal
7w, perineal body
anal membrane (8w end ruptured)
cloacal membrane
urogenital membrane
congenital anomalies:
• urorectal septum incomplete separation
2) the anal canal
superior 2/3 derived form the hindgut
inferior 1/3 derived from proctodeum
pectinate line
different in blood supply, nerve supply & lymphatic drainage
congenital anomalies:
• congenital aganglionical megacolon (Hirschsprung disease)
intermediate mesoderm → urogenital ridge
nephrogenic cord → the urinary system
genital ridge → the genital system
I. Urinary System
1. kidney & ureters
1) pronephros
rudimentary & nonfunctional
(1) pronephros
4W beginning
4W end
cervical region:nephrotomes (生肾节)→ pronephros → regress
(2) pronephric ducts
→ persist
2) mesonephros interim kidneys
(1) mesonephros
4W late
caudal region: nephrogenic cord(生肾索)→ mesonephric tubules → regress
(2) mesonephric (Wolffian) ducts
pronephric ducts → mesonephric ducts
fused with cloaca
3rd month end → degenerate
♂ a few persist → male genital system
3) metanephros permanent kidneys
(1) primordium 5th week
ureteric buds (metanephric diverticulum)
metanephric blastema (metanephric mass of intermediate mesoderm)
reciprocal induction
9w, produce urine
a. ureteric buds — collecting system
outgrowth from the mesonephric duct
bifurcate: ureters → collecting tubules
b. metanephric blastema - excretory units
derived from the nephrogenic cord
metanephric vesicles → metanephric tubules
proximal end: → Bowman's capsule
+ glomeruli → nephrons
distal end: contact with arched collecting tubule
congenital anomalies:
• bilateral renal agenesis
oligohydramnios; Potter’s syndrome
• unilateral renal agenesis
• renal dysplasias
• duplication of the ureter
• multicystic dysplastic kidney: urinary tract obstruction
• congenital polycystic kidney: autosomal recessive condition
(2) position change of the kidney
ascent of the kidney: pelvis → abdomen
rotation: 90°, ventrally → anteromedially
congenital anomalies:
• ectopic kidneys
• horseshoe kidney
(3) blood supply of the kidney
branches of the common lilac A. → disappear
distal end of the aorta → disappear
accessory renal A.
cranial arterial branches (from the abdominal aorta) → renal arteries
2. bladder & urethra
4-7W urorectal septum
cloaca → the urogenital sinus + the anal canal
1) urogenital sinus
vesical part → bladder
pelvic part + phallic part → urethra
2) bladder
vesical part of urogenital sinus enlarge
allantois → urachus → median umbilical ligament
distal portions of the mesonephric ducts → trigone
congenital anomalies:
• urachal fistula, cyst, sinus
3) urethra
pelvic part: ♂prostatic & membranous urethra;♀: membranous urethra
phallic part: ♂: penile urethra;♀: vestibule of vagina
congenital anomalies:
• exstrophy of the bladder
3. the suprarenal glands
mesoderm → fetal cortex → regresses (1yr)
neural crest cells → medulla
permanent cortex: →zona glomerulosa+ zona fasciculata + zona reticularis (3yr end)
II. Genital System
• sex determination
SRY gene (sex-determining region of the Y chromosome): testis-determining factor
• sex development
indifferent stage
different stage
1. indifferent stage --- primodium
1) gonads
• coelomic epithelium (posterior abdominal wall )
gonadal ridge
• underlying mesenchyme
• primordial germ cells
(1) primordial germ cells
endoderm cells in the wall of the yolk sac migration → gonadal ridge
(2) gonadal ridge
primitive sex cords
2) genital ducts
• mesonephric ducts (Wolffian ducts)
• paramesonephric ducts (Mullerian ducts): longitudinal invagination of the
coelomic epithelium
cranial end: opens into the body cavity
caudal ends: two fused → uterine canal
tip:  sinus tubercle
3) external genitalia
• genital tubercle → phallus
• urethral folds
• labioscrotal swellings
urethral groove
2. different stage
1) male
(1) testis
the primitive sex cords: → medullary cords → Sertoli cells (epithelium)
primordial germ cells: → spermatogonia
mesenchyme: → Leydig cells → testosterone
→ tunica albuginea
(2) genital ducts
• mesonephric ducts: ∵ testosterone ∴develop
mesonephric ducts → ductus epididymis + ductus deferens
mesonephric tubules → ductuli efferentes
• paramesonephric ducts: ∵antimullerian hormone (AMH) ∴regress
(3) external genitalia
testosterone → dihydrotestosterone
phallus → penis
urethral folds → corpus spongiosum
labioscrotal folds → scrotum
urethral groove → penile urethra
congenital anomalies:
• hypospadias
• epispadias
(4) descent of the testes
posterior abdominal wall → inguinal canal → scrotum
peritoneal sac → vaginal process →tunica vaginalis & proximal part obliterated
congenital anomalies:
• congenital inguinal hernia;hydrocele
failure of closure of the processus vaginalis
• cryptorchidism
• ectopic testes
2) female
(1) ovary
no Y chromosome, no SRY
primitive sex cords → regress
surface epithelium → secondary sex cords (cortical cords)+ oogonia → follicles
mesenchyme → stromal cells
(2) genital ducts
mesonephric duct: no testosterone → regress
paramesonephric duct: no AMH → develop
paramesonephric duct → uterine tube + uterovaginal primordium
uterovaginal primordium → corpus and cervix of the uterus
+ upper portion of vagina
sinus tubercle induced → sinovaginal bulbs (from urogenital sinus)
sinovaginal bulb → vaginal plate → vagina (lower 2/3)
congenital anomalies:
abnormal development of the uterus
absent of the vagina & uterus
vaginal atresia
imperforate hymen
(3) external genitalia
genital tubercle → clitoris
urethral folds
→ labia minora
labioscrotal swellings → labia majora
(4) descent of the ovaries
abdominal → pelvic
gubernaculums → ovarian ligament + round ligament of uterus
3) congenital anomalies in sex differentiation
phenotype ≠ Epi type; gonad ≠ external genitalia
(1) true hermaphroditism
ovary & testes / ovotestes; external genital is ambiguous
(2) pseudohermaphrodites
• female pseudohermaphroditism
46, XX; chromatin-positive nuclei (sex chromatin, Barr body)
external genitalia: masculinization
congenital adrenal hyperplasia (produced by suprarenal gland )
• male pseudohermaphrodites
46, XY chromatin- negative nuclei
internal and external genitalia variable
inadequate production of androgenic hormones & AMH
• androgen insensitivity syndrome (testicular feminization syndrome);
46, XY
external genitalia are female
virgina ends blindly; uterus & uterine tube absent
lack of androgen receptors
Three features:
• Developing early
• Mostly from mesoderm
• Obvious changes after birth
I. Development of primordial cardiovascular system
1. Development of Early Blood Vessels (angiogenesis) 3w
Extraembryonic mesoderm of the yolk sac, connecting stalk and chorion → blood
islands → canalized → vessels endothelia and primitive blood cells
13-15d: extraembryonic angiogenesis
2d later: intraembryonic angiogenesis
2. Development of Primitive Heart Tube
Primordium: Cardiogenic area
paired angioblastic cord → endocardial heart tubes
Intraembryonic coelom → pericardial coelom
Lateral fold: 2 heart tubes →single heart tube
Head fold: cranial → caudal & ventral
3. Primitive cardiaovascular system
Form: middle of 3w
Function: beginning of 4w
Three separate circulations: vitelline, chorionic, and intraembryonic.
II. Development of the heart
1. Primodium: Endocardial heart tube
1) Origin: splanchnic mesoderm and neural crest cells
Endothelium → endocardium
Cardiac jelly → subendocardial tissue
Primordial myocardium (Myoepicardial mentle) →myocardium, epicardium
2) Endocardial heart tube fusion
from cranial to caudal at 4w
Dorsal mesocardium → transverse pericardial sinus
2. Looping of the heart
Truncus arteriosus
Bulbus cordis Bulboventricular loop
(cephalic portion bends ventrally, caudally and slightly to the right)
Atrium → dorsocranially and bulges laterally on each side of bulbus
Sinus venosus
Congenital anomalies: Dextrocardia; Acardoa; Ectopic cordis
3. Partitioning of the heart
1) Division of atrioventricular canal
Subendocardial tissue → 2 endocardial cushions → fuse → right and left canals
2) Partitioning of the atria
Septum primum → endocardial cushions → foramen primum
Septum primum absorbed → foramen secundum → foramen primum closing
Septum secundum → cover the foramen secundum → foramen ovale
Congenital anomalies: Atrial septal defects (ASD)
3) Repositioning of the sinus venosus
Left to right shunts
Right horn enlarged ――――――――
Left horn diminished
Smooth part of right atrium
Coronary sinus
Primordial RA → rough part
Primordial LA → left auricle (primordial pulmonary vein → smooth part of LA)
4) Partitioning of the ventricles
Primordial interventricular septum (IVS) 5w → Muscular part of IVS
IV foramen 7w
Congenital anomalies:
Ventricular septal defects (VSD): most common, especially membranous part
5) Partitioning of the outflow tract of the heart
Right and Left Truncal ridges + Bulbar ridges
↓ fuse
aorticopulmonary septum
180o spiraling
pulmonary trunk → right ventricle
aorta → left ventricle
Bulbus cordis → Conus arteriosus of RV,Aortic vestibule of LV
Truncus swellings → semilunar valves
Congenital anomalies:
Truncus arteriosus:Accompanied by VSD
Transposition of the great arteries
Unequal division of the truncus ateriorsus
Tetralogy of Fallot:pulmonary stenosis,VSD,overriding aorta,AV hypertrophy
4. Conducting system of the heart
Right wall of sinus venosus → Sinuatrial node (5w)
Left wall of sinus venosus → AV node & bundle
III. Development of arteries
Vitelline artery
Aortic sac → Aortic arches → Dorsal arota →30 pairs intersegmental arteries
Umbilical artery
1. Vitelline artery
Celiac artery (truncus coeliacus), A. Mesenterica superior, A. Mesenterica inferior
2. Umbilical artery
Proximal parts → A. iliaca interna, A. vesicales superiores
Distal parts → Lig. Umbilica media
3. Intersegmental arteries
Neck → A. vertebralis (7th →A. subclavia)
Thorax → A. intercostalis
Abdomen → A. lumbar (5th → A. iliaca commnis)
Sacral region → A. sacrales laterals
4. Aortic arches
→ A. maxillary, A. carotis externa
2) 2
→ A. stapedia
3) 3
proximal → A. carotis communis
distal → A. carotis interna (along with dorsal aortae)
4) 4
left → arch of aorta
right → A. subclavia dextra (along with dorsal aorta & 7th IS artery)
left 7th IS artery → A. subclavia sinistra
5) 5 → degenerate
6) 6th
proximal → A. pulmonalis sinistra
→ ductus arteriosus (lig. Arteriosum)
right proximal → A.pulmonalis dextra
distal → degenerate
Congenital anomalies:
Coarctaton of the aorta (mostly Juxtaductal coarctation); Double aortic arch;
Right arch of aorta; Anomalous right subclavian artery
IV. Development of veins
Vitelline veins
Sinus venosus ←
Umbilical veins
Common cardinal veins (CCV) ←
anterior (ACV)
posterior (PCV)
1. Vitelline veins
Hepatic vein ←Cranial R.
Cranial L →
Middle R →
Hepatic sinusoids
← Middle L
Caudal R. → Anastomotic network ← Caudal L
Portal vein
2. Umbilical veins
Cranial R. ---------- Cranial L. → Regressed
Caudal R ----------- Caudal L. → Ductus venosus
Umbilical vein
3. Cardinal veins
L. brachiocephalic v.
Anastomotic shunt
Coronary sinus
← CCV L. → Sinus venosus ← CCV R.
← PCV L.
PCV R.→ Root of Azygos v.
Iliac Anastomosis
Common iliac v.
Subcardinal veins → L. Renal v., Superenal v., Gonadal v., IVC
Anastomosis → L. Renal v., IVC
Supracardinal veins → Azygos v., Hemiazygos v, IVC
4 segments of inferior vena cava
Hepatic segment ← Heptic vein
Prerenal segment ← R. subcardinal v.
Renal segment ← Anastomosis
Postrenal segment ← R. supracardinal v.
Anomalies: Double SVC; Left SVC
V. Fatal and neonatal circulation
1. Fetal circulation
Placental circulation with umbilical A. & V.
Ductus venosus
Foramen ovale
Ductus arteriosus
2. Neonatal circulation
Pulmanary circulation
Ductus venosus → Lig. venosus
Foramen ovale → Oval fossa
Ductus arteriosus → Lig. arteria
Congenital anomalies: Patent Ductus Arteriosus (PDA)
I. Origin of the nervous system
1. inducer: notochord and paraxial mesoderm
2. ectoderm cells (overnotochord)
neural plate
neural groove & neural fold closure neural tube → CNS
4th pair of somites
cranial 2/3 → brain
caudal 1/3 → spinal cord
 rostral (anterior) neuropore: closed by 25-26 days
 caudal (posterior) neuropore: closed by 27-28 days
1) lumen of the neural tube → ventricular cavities of the brain & central canal of
the spinal cord
2) wall of the neural tube (neuroepithelium) → nervous tissue
3) mesenchyme surrounding the neural tube → meninges
3. neural crest → PNS
II. Histological differentiation of cells in CNS
early neuroblasts (apolar ~ → bipolar ~ → unipolar ~ ) →
neuroepithelial cells
→ astroblasts → astrocytes
ependymal cells
late glioblasts → oligodendroblasts → oligodendrocytes
 ventricular zone (ependymal layer)
 intermediate zone (mantle layer)
axons & glial cells → marginal zone (layer)
III. Development of the spinal cord
1. the appearance of the spinal cord in adult
2. the development of the spinal cord
1) the development of the spinal cord
from caudal 1/3 of the neural tube
(1) lumen of the neural tube → central canal of the spinal cord
(2) mantle layer → gray matter of the spinal cord
proliferation and differentiation of the neuroepithelial cells in the mantle layer
causes the formation of:
a. alar plates (dorsal, sensory)→ dorsal gray columns (horns)
b. roof plates
sulcus limitans
c. basal plates (ventral, motor)→ ventral gray columns (horns) &
lateral (intermediate) columns (horns)
d. floor plates
(3) marginal layer → white matter of the spinal cord
2) development of spinal ganglia and nerves
(1) neural crest cells → bipolar neuroblasts → unipolar afferent neuron →
spinal ganglia
(2) the peripheral processes → spinal nerves
(3) the central processes → the dorsal roots of the spinal nerves
(4) neural crest cells → satellite cells & schwann cells
3) development of spinal meninges
mesenchyme surrounding the neural tube → meninges
(1) external mesenchyme → dura mater
(2) neural crest cells + internal mesenchyme → leptomeninges
(arachnoid mater + pia mater)
subarachnoid space & cerebrospinal fluid (CSF)
4) positional changes of the spinal cord and formation of the cauda equina
because the vertebral column and dura mater grow more rapidly than the spinal
cord, the caudal end of the spinal cord lies at the level of
(1) 1st sacral lumbar vertebra at 24 weeks prenatal
(2) 2nd to 3rd lumbar vertebra in the newborn
(3) the inferior border of 1st lumbar vertebra in the adult
(4) nerve roots inferior to the end of the spinal cord form a sheaf --- cauda equina
5) myelination of nerve fibers
4th months prenatal to 1st year postnatal
schwann cells & oligodendrocytes
6) congenital anomalies of the spinal cord
spina bifida: defective closure of the neural tube (NTD), meninges, vertebral
arches, muscles and skin
(1) spina bifida occulta (隐性脊柱裂)
(2) spina dermal sinus (脊皮窦)
(3) spina bifida cystica (囊性脊柱裂)
a. spina bifida with meningocele (脊柱裂合并脊膜膨出)
b. spina bifida with meningomyelocele (脊柱裂合并脊膜脊髓膨出)
sphincter paralysis (saddle anesthesia, lumbosacral meningomyelocele)
c. spina bifida with myeloschisis (脊柱裂合并脊髓裂)
IV. Development of the brain
1. The appearance of the brain in adult
2. The development of the brain
1) primary brain vesicles (4th week)
midbrain flexure & cervical flexure
(1) forebrain (prosencephalon) (前脑泡)
(2) midbrain (mesencephalon) (中脑泡)
(3) hindbrain (rhombencephalon) (菱脑泡)
2) secondary brain vesicles (5th week)
pontine flexure
(1) forebrain  telencephalon (端脑) + diencephalon (间脑)
(2) midbrain  mesencephalon (中脑)
(3) hindbrain  metencephalon (后脑) + myelencephalon (末脑)
3) the development of brain vesicles
(1) myelencephalons (末脑) → medulla oblongata
canal → central canal of the spinal cord
a. caudal part alar plate → gracile nuclei + cuneate nuclei
(close part) ventral area → pyramids
canal → lower part of 4th ventricle
b. rostral part alar plate → 4 sensory nuclei
(open part) basal plate → 3 motor nuclei
c. pia mater
→ tela choroidea → choroid plexus
roof plate
(2) metencephalon (后脑)
a. canal → upper part of 4th ventricle
b. alar plate → 3 sensory nuclei & pontine nuclei
c. dorsal part of alar plate → rhombic lip→ cerebellar plate (fuse)→ cerebellum
d. basal plate → 3 motor nuclei
e. ventral area → pons
(3) mesencephalon (中脑)
a. canal → cerebral aqueduct
b. alar plate → tectum (顶盖) → superior colliculi (上丘) + inferior colliculi
c. basal plate → tegmentum (被盖) → red nuclei etc
(4) diencephalon (间脑)
a. canal → posterior part of 3rd ventricle
b. roof plate → pineal body
c. alar plate →
hypothalamus → pituitary gland
d. the development of the pituitary gland
neuroectoderm floor of the diencephalons
ectodermal roof of the
neurohypophysial bud
hypophysial pouch (Rathke
pituitary gland
craniopharygioma (颅咽管瘤)
e. pia mater
→ tela choroidea → choroid plexus
roof plate
(5) telencephalon (端脑)
one median portion and two lateral diverticula
lamina terminalis (终板)
a. canal → anterior part of 3 ventricle, lateral ventricle
b. floor part → corpus striatum (纹状体)
c. pia mater
→ tela choroidea → choroid plexus
roof plate
d. CSF circulation
e. phylogeny (种系发生) of cerebrum
archeopallium (古皮质), palaeopallium (旧皮质), neopallium (新皮质)
4) congenital anomalies of the brain
(1) cranium bifidium (颅裂)
(2) cranial meningocele (脑膜膨出)
(3) meningoencephalocele (脑膜脑膨出)
(4) anencephaly (无脑畸形): defective closure of the neural tube (NTD),
(5) hydrocephalus (脑积水)
(6) hydranencephaly (积水性无脑畸形)
(7) microcephaly (小头畸形)
(8) holoprosencephaly (前脑无裂畸形)
V. Development of the PNS
originate from the neural crest
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