Transcript Malformation

EMBRYOLOGY 4
2009
Prenatal period
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Gametogenesis
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Preimplantation period and implantation (till the
end of second week)
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Embryonic period
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Fetal period
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(Birth
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Perinatal period)
Estimation of fetal age
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Last menstrual period
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Fertilization
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Ultrasound examination
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Estimation according to the morphologic characteristics
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Length - 3th – 4th week – only distance
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Later: crown-rump length (CRL)
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Fetal period : Biparietal diameter, head circumference,
abdominal circumference, femur length, foot length
Carnegie stages
Organogenesis: 3.-8. week
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Formation of all basic organ systems:
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Cardiovascular and nervous - 3.week
External genitalia – later than 8.week
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Changes in outer shape
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Most critical period
Formation of 3D shape
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Head fold
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Tail fold
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Lateral folds
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Head fold - growth of brain and spinal cord – folding (septum
transversum and heart are pushed ventrally)
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Changes in shape of intraembryonic coelomic cavity
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Tail fold – cloacal membrane is also pushed ventrally
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Lateral folds – gut closure, formation of umbilical cord
Derivatives of the three germ
layers
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Ectoderm – CNS, PNS, retina, epidermis, mammary gland,
enamel
Cells of neural crest -– ganglia, Schwann cells, melanocytes,
medulla of suprarenal gland, meninx, muscle, connective
tissue and cartilages/bones of pharyngeal arches
Mesoderm – connective tissue, cartilage, bone, muscle,
vessels, kidney, ovary, testes spleen, cortex of suprarenal
gland, mesothel
Endoderm – digestive and respiratory system, thyroid gland,
parathyroid gland, thymus, pancreas, liver, urinary bladder
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4
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week
Closure of rostral and caudal neuroporus (24th and 26th
day)
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Somites (4.-12.)
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Pharyngeal arches visible by 26th day
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Heart prominence
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Upper limb buds 26th- 27th day
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Otic pits and lens placodes
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Lower limb buds – by the end of week
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5
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week
Head growth – brain and pharyngeal arches
Pharyngeal arches – development of face and
neck
Ectodermal grooves and endodermal pouches,
pharyngeal membranes
Aortic arches – vessels in pharyngeal arches
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6
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week
Development of limbs – future fingers – digital
rays are visible
Development of ear: external acustic meatus (first
pharyngeal groove), swelling around it fuse to
form auricle
Head is larger than body
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7
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week
Development of limbs – digits in upper limbs
Umbilical herniation– intestine enters the
extraembryonic coelom in the proximal region of
umbilical cord.
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8
week
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Digits also in lower limbs
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Tail disappears at the end of 8th week
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Embryo has distinct human characteristics – head
constitutes almost ½ of embryo
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Eyes - lids fuse by end of 8th week
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External genitalia - indifferent
Fetal period
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By 9th week till birth
Biparietal distance, head circumference,body
circumference, femur length,
Disorder – IUGR – intrauterinne growth
retardation – reduction of vascular supply,
placental insufficiency
Sclerotome development
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Notochord and neural tube induce development of
sclerotome – vertebrae – split and recombine to form
intersegmental vertebral rudiment – vertebrae and
interververtebral discs – signal molecule - Shh
Neural tube and superficial ectoderm – induce
development of dermomyotome - Wnt
Development of vertebrae
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Vertebrae develop from sclerotome
Mesenchymal tissue from sclerotom surrounds
notochord (nucleus pulposus)
Vertebral body forms from the cranial and caudal
halves of two succesive sclerotomes
Development of limbs
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Limb buds – interaction between
mesenchyme and ectoderm – hox
Apical ectodermal ridge (TGFβ and BMF, retinoic
acid) – gradient of morphogens concentration
Formation of paddlelike hand or foot plate – digital
rays + notches – membrane webbing digits apoptosis
Mesenchyme in the middle od limb anlage –
chondrogenic blastema
Limb bud
Development of limbs
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Vascular supply – intersegmental artery - primary
axial artery – marginal sinus
Motoric inervation – from relevant segment,
fibres (axons) are pulled by migrating myoblasts
Sensoric fibres growth along motoric fibres to
rich cells from dermatome
Development of limbs
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Joints – apoptosis - synovial tissue – formation of knee/elbow
Rotation of limbs – upper limbs rotates laterally, lower limbs
rotate medially
Muscles from hypaxial portio of myotomes – dorsal muscles
– extensors, supinators and abductors, ventral – flexors,
pronators and adductors
Aggregation of cells in the middle of limb – chondrogenic
blastema
Primary osiffication centers in the long bones - 7th week
Malformations
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Critical period is 24- 36 day after fertilization
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Syndaktyly, polydaktyly
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Amelia, meromelia
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Inborn defect of radius
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Brachydactyly
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Inborn talipes
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Hip dysplasia
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Causes: genetic, oligohydramion, teratogens
Teratology
Teratology is the science that studies the causes,
mechanisms, and patterns of abnormal
development.
 Developmental disorders present at birth are called
congenital anomalies, birth defect or congenital
malformation.
 Congenital anomalies are of four clinically significant
types: malformation, disruption, deformation and
dysplasia.
Teratology - terms
 Malformation is a primary structural defect resulting from
a localized error of morphogenesis
 Disruption is specific abnormality that results from
disruption of normal developmental processes It depends on
time not on agent
 Deformation is an alteration in shape / structure of
previously normally formed part
 Syndrome is a recognized pattern of malformations
with a given ethiology.
Malformation incidence
 3% of all live-born infants have an major anomaly
 Additional anomalies are detected during postnatal live
– about 6% at 2 year, 8% in 5year, other 2% later
 Single minor anomalies are present in about 14% of
newborns 3%
 Major malformation are more frequent in early embryos
(15%) than in newborns. They are lost during
first 6 to 8 weeks.
Genetic factors
 Chromosomal aberrations are common and are present in
6 to 7% of zygotes – (result =abort)
 Numerical chromosomal abnormalities – usually nondisjunction- error in cell division
Down syndrome (21) Edwards (18) Patau (13) Turner
(X0), Klinenfelter (XXY)
 Structural chromosomal abnormalities – chromosome
breaks = translocation, deletion (cri du chat syndrome),
duplication, inversion.
 Mutant genes – achondroplasia, fragile-X syndrome
Anomalies caused by environmental
factors
 Teratogens are exogenous agents that may cause developmental
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defects:
Drugs (warfarin, valproic acid, phenytoin, vitamine A, thalidomide,
cytostatic drugs /cyclophosphamide/, lithium carbonate)
Chemicals (PCBs, methylmercury, alcohols)
Infections (rubella, cytomegalovirus, herpes virus, toxoplasma,
syphilis)
Ionizing radiation (X-rays)
Maternal factors (diabetes mellitus, hyperthermia, phenylketonuria,
hyper-/hypo-thyreosis)
Basic principles in teratogenesis
 Critical period of development
 Sensitive period
 Dosage of the drug or chemical
 Genotype (genetic constitution) of the embryo and
mother
Consequences of exposure to
teratogens
 Death – abortion or
miscarriage
 Malformation
 IUGR – intrauterine
growth retardation
 Functional defects in
the newborn
 Normal newborn
Drugs with prooved effect on embryo or
fetus
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Thalidomide
Cytostatics
Warfarin and other coumadine derivatives
Antiepileptic drugs
Retinoids and vit. A
Alcohols
Androgens
Diethistilbestrol
Antagonists of folic acid (aminopterin)
Lithium
Ribavirin
ACE inhibitors
NSAIDs