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Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

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Page 1: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Lecture 1:From Fertilization to

Gastrulation

Page 2: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

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!

Page 3: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

1st Prenatal Visit: 8 Weeks

Page 4: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The First Week

Page 5: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

From the Morula Stage to Compaction

Morula (3 Days) Compacted Embryo

Page 6: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Formation of the Blastocyst and Implantation

Blastocyst (4-5 Days) Implanting Blastocyst (6 Days)

Syncytiotrophoblast

Cytotrophoblast

Page 7: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Hydatidiform Moles

• Formed from trophoblast

• Paternal genome (genomic imprinting)

• Secrete high levels of hCG (syncytiotrophoblast)

• May become invasive (choriocarcinomas)

Page 8: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

First Week of Development

Page 9: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sites for Ectopic Pregnancies

Page 10: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Tubal Pregnancy

Page 11: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Ectopic Pregnancy in the Rectouterine (Douglas) Pouch

Page 12: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

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.

Page 13: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

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)

Page 14: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

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

Page 15: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

0

20

40

60

80

100

120

LBW VLBW Preterm

% a

dv

ers

e p

eri

na

talo

utc

om

es

Singletons Twins Triplets +

Percentage of Adverse Perinatal Outcomes among ART Infants by Plurality -- US, 2002

Page 16: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Percent LBW among ART singletons (1996-1997) compared to all singleton births to

non-teen mothers in US (1997)

13.2

2.6

5.7

1

0

5

10

15

LBW VLBW

Per

cen

t

ART

USPopulation

Schieve et al., N Engl J Med 346:731-7, 2002

Page 17: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Large Meta-Analysis Study

30-40% Increased Risk of Birth Defects from ART

From: Hansen et al., Human Reproduction, 20: 328, 2005

Page 18: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Implantation with Formation of Two Layers in the Embryoblast and the Trophoblast

Implanting Blastocyst (6 Days) Implanted Embryo (7.5 Days)

Page 19: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Early Trophoblast (Placental) and Embryonic Development

9 Days

12 Days

13 Days

Yolk sac cavity

Oropharyngeal

membrane

Page 20: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

15 days15 Days

2nd Week = Week of Two’s

Cytotrophoblast: Syncytiotrophoblast & Cytotrophoblast

Extraembryonic Mesoderm: Visceral (splanchnic) & Parietal (somatic) Layers

Embryonic Disc: Epiblast & Hypoblast

(Parietal layer)

Extraembryonic

mesoderm (Visceral layer)

Page 21: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Formation of the Primitive Streak and Establishment of the Cranial-Caudal Axis

Page 22: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

BMPs: Hatched area = ventral mesoderm (kidneys and body wall) and ectoderm

BMPs (goosecoid, brachyurea T) = dorsal mesoderm (somites) and neural ectoderm

Anterior Visceral Endoderm (AVE) Induces the Cranial Region

Page 23: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Overexpression of Goosecoid in Frogs Causes Double-Headed Tadpoles: Does It Cause This Defect in Humans?

Page 24: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Genetic Regulation of Laterality

Page 25: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Situs Inversus Kartagener syndrome (20%) Cilia malfunction with situs inversus (bronchiectasis and sinusitis)

Laterality Sequences Left or right sidedness Asplenia (right) Polysplenia (left)

Page 26: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Gastrulation: Formation of the 3 Germ Layers

14 Days 16 Days

Oropharyngeal membraneOropharyngeal

membrane

Page 27: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

During Gastrulation, Epiblast Cells Move Toward the Primitive Streak, Leave the Epiblast, and Create 2 New Layers

Oropharyngeal membrane

Page 28: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Formation of the Prechordal Plate and Notochord

Oropharyngeal membrane

Oropharyngealmembrane

Page 29: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Formation of the Notochord

A

Cut lines for C B

Oropharyngeal membrane

Page 30: Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lecture 1: From Fertilization to Gastrulation

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Three Germ Layers

Mesoderm

EndodermNotochord (Part of the mesoderm)

Ectoderm

• 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.)