Lecture 1: From Fertilization to Gastrulation
Copyright © 2019 Wolters Kluwer • All Rights Reserved 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! Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved 1st Prenatal Visit: 8 Weeks Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved The First Week Copyright © 2019 Wolters Kluwer • All Rights Reserved
From the Morula Stage to Compaction Morula (3 Days) Compacted Embryo Copyright © 2019 Wolters Kluwer • All Rights Reserved
Formation of the Blastocyst and Implantation Syncytiotrophoblast Cytotrophoblast Blastocyst (4-5 Days) Implanting Blastocyst (6 Days) Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Hydatidiform Moles Formed from trophoblast Paternal genome (genomic imprinting) Secrete high levels of hCG (syncytiotrophoblast) May become invasive (choriocarcinomas) Copyright © 2019 Wolters Kluwer • All Rights Reserved
First Week of Development Copyright © 2019 Wolters Kluwer • All Rights Reserved
Sites for Ectopic Pregnancies Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Tubal Pregnancy Uterine tube Ampullary region Copyright © 2019 Wolters Kluwer • All Rights Reserved
Ectopic Pregnancy in the Rectouterine (Douglas) Pouch Copyright © 2019 Wolters Kluwer • All Rights Reserved
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. Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved 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) Copyright © 2019 Wolters Kluwer • All Rights Reserved
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 Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved
Large Meta-Analysis Study 30-40% Increased Risk of Birth Defects from ART From: Hansen et al., Human Reproduction, 20: 328, 2005 Copyright © 2019 Wolters Kluwer • All Rights Reserved
Implantation with Formation of Two Layers in the Embryoblast and the Trophoblast Implanting Blastocyst (6 Days) Implanted Embryo (7.5 Days) Copyright © 2019 Wolters Kluwer • All Rights Reserved
Early Trophoblast (Placental) and Embryonic Development 9 Days 13 Days 12 Days Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Extraembryonic mesoderm (Visceral layer) (Parietal layer) 15 Days 2nd Week = Week of Two’s Cytotrophoblast: Syncytiotrophoblast & Cytotrophoblast Extraembryonic Mesoderm: Visceral (splanchnic) & Parietal (somatic) Layers Embryonic Disc: Epiblast & Hypoblast Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Formation of the Primitive Streak and Establishment of the Cranial-Caudal Axis Copyright © 2019 Wolters Kluwer • All Rights Reserved
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 Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Overexpression of Goosecoid in Frogs Causes Double-Headed Tadpoles: Does It Cause This Defect in Humans? Copyright © 2019 Wolters Kluwer • All Rights Reserved
Genetic Regulation of Laterality Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved Situs Inversus Kartagener syndrome (20%) Cilia malfunction with situs inversus (bronchiectasis and sinusitis) Laterality Sequences Left or right sidedness Asplenia (right) Polysplenia (left) Copyright © 2019 Wolters Kluwer • All Rights Reserved
Gastrulation: Formation of the 3 Germ Layers 14 Days 16 Days Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved During Gastrulation, Epiblast Cells Move Toward the Primitive Streak, Leave the Epiblast, and Create 2 New Layers Copyright © 2019 Wolters Kluwer • All Rights Reserved
Formation of the Prechordal Plate and Notochord Cranial Caudal Copyright © 2019 Wolters Kluwer • All Rights Reserved
Formation of the Notochord Copyright © 2019 Wolters Kluwer • All Rights Reserved
Copyright © 2019 Wolters Kluwer • All Rights Reserved The Three Germ Layers Mesoderm Endoderm Notochord (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.) Copyright © 2019 Wolters Kluwer • All Rights Reserved