Lecture 1 From Fertilization to Gastrulation

From Fertilization to Gastrulation: 

From Fertilization to Gastrulation

Why Embryology?: 

Why Embryology? Birth defects are a major contributor to mortality and 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 3-6/100 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! And physicians play a major role and women say they will do what doctors tell them.

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1 st 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 Blastocyst (4-5 Days) Implanting Blastocyst (6 Days) Syncytiotrophoblast Cytotrophoblast

Hydatidiform moles: 

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 Uterine tube Uterine tube: Most common site (95%) Rectouterine pouch (Douglas’ pouch): Most common site in the peritoneal cavity

Assisted Reproductive Technologies (ART): 

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

ART Cycles Performed, Live-Birth Deliveries, and Live Babies Born Using ART -- US, 1996-2002: 

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 USA (1.1% of all births)

Adverse Outcomes Potentially Associated With ART: 

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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Low birth weight (LBW) in ART pregnancies is partly due to an increase in multiple births (twins, triplets, etc)… …but even singleton births in ART pregnancies have a higher incidence of LBW

Large Meta-analysis Study (an analysis of existing studies in the literature): 

Large Meta-analysis Study (an analysis of existing studies in the literature) 30-40% Increased Risk of Birth Defects from ART From: Hansen et al., Human Reproduction, 20: 328, 2005

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

Implantation with Formation of Two Layers in the Embryoblast and the Trophoblast Implanting Blastocyst (6Days) Implanted Embryo (7.5 Days)

Early Trophoblast (Placental) and Embryonic Development: 

Early Trophoblast (Placental) and Embryonic Development 9 Days 12 Days 13 Days Yolk sac cavity Oropharyngeal membrane

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15 days 15 Days 2 ND 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)

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15 Days Oropharyngeal membrane Primitive node Formation of the Primitive Streak and establishment of the Cranial-Caudal Axis (The “Organizer”)

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Overexpression of Goosecoid in frogs causes double headed tadpoles: Does it cause this defect in humans?

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BMPs: Hatched Area = ventral mesoderm (kidneys & body wall) & ectoderm BMPs (Goosecoid, Brachyurea T) = dorsal mesoderm (somites) & neural ectoderm Anterior Visceral Endoderm (AVE) Induces the Cranial Region (OTX1, LIM1, HESX1)

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Genetic Regulation of Laterality Oropharyngeal membrane 5HT

Situs Inversus Kartagener Syndrome(20%) Cilia malfunction with situs inversus (Bronchiectasis & Sinusitis) Laterality Sequences Left or Right Sidedness Asplenia(right) Polysplenia(left): 

Situs Inversus Kartagener Syndrome(20%) Cilia malfunction with situs inversus (Bronchiectasis & Sinusitis) Laterality Sequences Left or Right Sidedness Asplenia(right) Polysplenia(left) Antidepressants like S elective S erotonin (5HT) R euptake I nhibitors ( SSRI s) may cause laterality defects, including heart abnormalities, by altering the establishment of laterality during the 3 rd week of development .

Gastrulation: Formation of the 3 Germ Layers: 

Gastrulation: Formation of the 3 Germ Layers 14 Days 16 Days Oropharyngeal membrane Oropharyngeal membrane

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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 A Cut lines for C B Oropharyngeal membrane

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Mesoderm Endoderm Notochord (Part of the mesoderm) Ectoderm The Three Germ Layers Ectoderm: skin, CNS, PNS, eyes, internal ear, neural crest cells(bones & 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.)