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

2. 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!

3. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 1 st Prenatal Visit: 8 Weeks

4. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins The First Week

5. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins From the Morula Stage to Compaction Morula (3 Days) Compacted Embryo

6. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Formation of the Blastocyst and Implantation Blastocyst (4-5 Days) Implanting Blastocyst (6 Days) Syncytiotrophoblast Cytotrophoblast

7. 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)

8. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins First Week of Development

9. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Sites for Ectopic Pregnancies

10. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Tubal Pregnancy

11. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Ectopic Pregnancy in the Rectouterine (Douglas) Pouch

12. 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.

13. 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)

14. 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

15. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

17. Large Meta-Analysis Study 30-40% Increased Risk of Birth Defects from ART From: Hansen et al., Human Reproduction, 20: 328, 2005

18. 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)

19. 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

20. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 15 days 15 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)

21. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Formation of the Primitive Streak and Establishment of the Cranial-Caudal Axis

22. 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

23. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Overexpression of Goosecoid in Frogs Causes Double- Headed Tadpoles: Does It Cause This Defect in Humans?

24. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Genetic Regulation of Laterality

25. 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)

26. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Gastrulation: Formation of the 3 Germ Layers 14 Days 16 Days Oropharyngeal membrane Oropharyngeal membrane

27. 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

28. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Formation of the Prechordal Plate and Notochord Oropharyngeal membrane Oropharyngeal membrane

29. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Formation of the Notochord A Cut lines for C B Oropharyngeal membrane

30. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 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.)