Download From Fertilization to Gastrulation

Lecture 1:
From Fertilization to
Gastrulation
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Why Embryology?
• Birth defects are the leading cause of infant mortality.
• Birth defects are a major contributor to morbidity,
including physical and mental handicaps.
• All women of childbearing age are at risk of having an
infant with a birth defect. The incidence rate is 6/100
births.
• Each of you will have contact with women of
childbearing age; either as a friend, as a companion,
or as a patient. Or you are one yourself.
• MANY BIRTH DEFECTS CAN BE PREVENTED!
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1st Prenatal Visit: 8 Weeks
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The First Week
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From the Morula Stage to Compaction
Morula (3 Days)
Compacted Embryo
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Formation of the Blastocyst and Implantation
Syncytiotrophoblast
Cytotrophoblast
Blastocyst (4-5 Days)
Implanting Blastocyst (6 Days)
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Hydatidiform Moles
• Formed from trophoblast
• Paternal genome (genomic imprinting)
• Secrete high levels of hCG
(syncytiotrophoblast)
• May become invasive (choriocarcinomas)
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First Week of Development
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Sites for Ectopic Pregnancies
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Tubal Pregnancy
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Ectopic Pregnancy in the Rectouterine (Douglas) Pouch
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Assisted Reproductive
Technologies (ART)
Fertility treatments in which both the eggs and
sperm are handled in the laboratory (i.e., in vitro
fertilization and related procedures). Eggs and
sperm are placed in a culture medium; fertilized
eggs are placed in the uterus.
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ART Cycles Performed, Live-Birth Deliveries, and
Live Babies Born Using ART—US, 1996-2002
115,392 procedures reported to CDC in 2002; 45,751 infants born after ART in US (1.1% of all births)
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Adverse Outcomes Potentially
Associated with ART
•
•
•
•
•
•
•
•
Embryo effects
Spontaneous abortions
Multiple births
Adverse perinatal outcomes: low birth weight,
preterm delivery (even among singleton births)
Birth defects
Developmental disabilities
Childhood malignancies
Longer term outcomes?
• Effects on puberty/future fertility
• Effects on chronic disease risk
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Percentage of Adverse Perinatal Outcomes
among ART Infants by Plurality -- US, 2002
% adverse perinatal outcomes
120
100
80
60
40
20
0
LBW
Singletons
VLBW
Twins
Preterm
Triplets +
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Percent LBW among ART singletons (1996-1997)
compared to all singleton births to
non-teen mothers in US (1997)
15
Percent
13.2
10
ART
5.7
US
Population
5
2.6
1
0
LBW
VLBW
Schieve et al., N Engl J Med 346:731-7, 2002
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Large Meta-Analysis Study
30-40% Increased Risk of Birth
Defects from ART
From: Hansen et al., Human Reproduction, 20: 328, 2005
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Implantation with Formation of Two Layers in the Embryoblast and the
Trophoblast
Implanting Blastocyst (6 Days)
Implanted Embryo (7.5 Days)
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Early Trophoblast (Placental) and Embryonic Development
Oropharyngeal
membrane
Yolk sac
cavity
9 Days
13 Days
12 Days
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Extraembryonic
mesoderm
(Visceral layer)
(Parietal layer)
15
15Days
days
2nd Week = Week of Two’s
Cytotrophoblast: Syncytiotrophoblast &
Cytotrophoblast
Extraembryonic Mesoderm: Visceral (splanchnic) &
Parietal (somatic) Layers
Embryonic Disc: Epiblast & Hypoblast
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Formation of the Primitive Streak and Establishment of the
Cranial-Caudal Axis
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Anterior Visceral Endoderm (AVE) Induces the Cranial Region
BMPs: Hatched area = ventral mesoderm
(kidneys and body wall) and ectoderm
BMPs (goosecoid, brachyurea T) = dorsal
mesoderm (somites) and neural ectoderm
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Overexpression of Goosecoid in Frogs Causes DoubleHeaded Tadpoles: Does It Cause This Defect in Humans?
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Genetic Regulation of Laterality
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Situs Inversus
Kartagener syndrome (20%)
Cilia malfunction with situs inversus
(bronchiectasis and sinusitis)
Laterality Sequences
Left or right sidedness
Asplenia (right)
Polysplenia (left)
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Gastrulation: Formation of the 3 Germ Layers
Oropharyngeal
membrane
Oropharyngeal membrane
14 Days
16 Days
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During Gastrulation, Epiblast Cells Move Toward the Primitive Streak,
Leave the Epiblast, and Create 2 New Layers
Oropharyngeal membrane
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Formation of the Prechordal Plate and Notochord
Oropharyngeal membrane
Oropharyngeal
membrane
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Formation of the Notochord
Cut lines for
C
B
Oropharyngeal
membrane
A
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The Three Germ Layers
Mesoderm
Ectoderm
Notochord Endoderm
(Part of the mesoderm)
• Ectoderm: skin, CNS, PNS, eyes, internal
ear, neural crest cells (bones and connective
tissue of the face and part of the skull)
• Mesoderm: bones, connective tissue,
urogenital system, cardiovascular system
• Endoderm: gut and gut derivatives (liver,
pancreas, lungs, etc.)
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