Ruling Emancipated Slaves and Indigenous Subjects: The Divergent Legacies of Forced Settlement and Colonial Occupation in the Global South Olukunle P. Owolabi
Recipient of the inaugural Henry Gray/Elsevier Distinguished Educator Award in 2007—the American Association of Anatomists’ highest award for excellence in human anatomy education at the medical/dental, graduate, and undergraduate levels of teaching; the Honored Member Award of the American Association of Clinical Anatomists (1994) for significant contributions to the field of clinically relevant anatomy; and the J.C.B. Grant Award of the Canadian Association of Anatomists (1984) “in recognition of meritorious service and outstanding scholarly accomplishments in the field of anatomical sciences.” In 2008 Professor Moore was inducted as a Fellow of the American Association of Anatomists. The rank of Fellow honors distinguished AAA members who have demonstrated excellence in science and in their overall contributions to the medical sciences. In 2012 Dr. Moore received an Honorary Doctor of Science degree from The Ohio State University; The Queen Elizabeth II Diamond Jubilee Medal honoring significant contributions and achievements by Canadians; and the Benton Adkins Jr. Distinguished Service Award for an outstanding record of service to the American Association of Clinical Anatomists.
T.V.N. (VID) PERSAUD
Recipient of the Henry Gray/Elsevier Distinguished Educator Award in 2010—the American Association of Anatomists’ highest award for excellence in human anatomy education at the medical/dental, graduate, and undergraduate levels of teaching; the Honored Member Award of the American Association of Clinical Anatomists (2008) for significant contributions to the field of clinically relevant anatomy; and the J.C.B. Grant Award of the Canadian Association of Anatomists (1991) “in recognition of meritorious service and outstanding scholarly accomplishments in the field of anatomical sciences.” In 2010 Professor Persaud was inducted as a Fellow of the American Association of Anatomists. The rank of Fellow honors distinguished AAA members who have demonstrated excellence in science and in their overall contributions to the medical sciences. In 2003 Dr. Persaud was a recipient of the Queen Elizabeth II Golden Jubilee Medal, presented by the Government of Canada for “significant contribution to the nation, the community, and fellow Canadians.”
MARK G. TORCHIA
Recipient of the Norman and Marion Bright Memorial Medal and Award and the Silver Medal of the Chemical Institute of Canada in 1990 for outstanding contributions. In 1993 he was awarded the TIMEC Medical Device Champion Award. In 2008 and in 2014 Dr. Torchia was a nominee for the Manning Innovation Awards, for innovation talent. Dr. Torchia’s most cherished award has been the Award for Teaching Excellence in 2011 from the Faculty of Medicine, University of Manitoba, and being asked to address the graduating class of 2014.
THE DEVELOPING HUMAN
CLINICALLY ORIENTED EMBRYOLOGY
10th Edition
Keith L. Moore, BA, MSc, PhD, DSc, FIAC, FRSM, FAAA
Professor Emeritus, Division of Anatomy, Department of Surgery
Former Professor and Chair, Department of Anatomy and Associate Dean for Basic Medical Sciences Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Former Professor and Head of Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Professor Emeritus and Former Head, Department of Human Anatomy and Cell Science Professor of Pediatrics and Child Health
Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Professor of Anatomy, St. George’s University, Grenada, West Indies
Mark G. Torchia, MSc, PhD
Associate Professor and Director of Development, Department of Surgery
Associate Professor, Department of Human Anatomy and Cell Sciences Director, Centre for the Advancement of Teaching and Learning, University of Manitoba, Winnipeg, Manitoba, Canada
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
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Library of Congress Cataloging-in-Publication Data Moore, Keith L., author.
The developing human : clinically oriented embryology / Keith L. Moore, T.V.N. (Vid) Persaud, Mark G. Torchia.—10th edition. p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-323-31338-4 (pbk. : alk. paper)—ISBN 978-0-323-31347-6 (international edition : alk. paper)
I. Persaud, T. V. N., author. II. Torchia, Mark G., author. III. Title.
[DNLM: 1. Embryology. QS 604]
QM601
612.6′4018—dc23
Content Strategist: Meghan Ziegler
Senior Content Development Specialist: Jennifer Ehlers
Publishing Services Manager: Patricia Tannian
Senior Project Manager: Kristine Feeherty
Design Direction: Margaret Reid
The cover images show a magnetic resonance image of a 27-week-old fetus in the uterus (Courtesy Dr. Deborah Levine, Beth Israel Deaconess Medical Center, Boston, Massachusetts). The photograph of the baby (Kennedy Jackson) was taken 7 days after her birthday. She is wrapped in a knitted cocoon that symbolizes the uterus.
Printed in the United States of America
2015001490
In Loving Memory of Marion
My best friend, wife, colleague, mother of our five children and grandmother of our nine grandchildren, for her love, unconditional support, and understanding. Wonderful memories keep you ever near our hearts. —KLM and family
For Pam and Ron
I should like to thank my eldest daughter, Pam, who assumed the office duties previously carried out by her mother, Marion. She has also been helpful in so many other ways (e.g., reviewing the text). I am also grateful to my son-in-law, Ron Crowe, whose technical skills have helped me utilize the new technology when I was improving this book.
For Gisela
My lovely wife and best friend, for her endless support and patience; our three children—Indrani, Sunita, and Rainer (Ren)—and grandchildren (Brian, Amy, and Lucas).
For Barbara, Muriel, and Erik
Nothing could ever mean more to me than each of you. Thank you for your support and your love.
For Our Students and Their Teachers
To our students: We hope you will enjoy reading this book, increase your understanding of human embryology, pass all of your exams, and be excited and well prepared for your careers in patient care, research, and teaching. You will remember some of what you hear, much of what you read, more of what you see, and almost all of what you experience.
To their teachers: May this book be a helpful resource to you and your students. We appreciate the numerous constructive comments we have received over the years from both students and teachers. Your remarks have been invaluable to us in improving this book.
Contributors
CONTRIBUTORS
David D. Eisenstat, MD, MA, FRCPC
Professor, Departments of Pediatrics, Medical Genetics and Oncology, Faculty of Medicine and Dentistry, University of Alberta; Director, Division of Pediatric Immunology, Hematology, Oncology, Palliative Care, and Environmental Health, Department of Pediatrics, Stollery Children’s Hospital and the University of Alberta; Inaugural Chair, Muriel and Ada Hole Kids with Cancer Society Chair in Pediatric Oncology, Edmonton, Alberta, Canada
Jeffrey T. Wigle, PhD
Principal Investigator, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre; Associate Professor, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
CLINICAL REVIEWERS
Albert E. Chudley, MD, FRCPC, FCCMG
Professor, Department of Pediatrics and Child Health; Professor, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
Michael Narvey, MD, FRCPC, FAAP
Section Head, Neonatal Medicine, Health Sciences Centre and St. Boniface Hospital; Associate Professor of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
FIGURES AND IMAGES (SOURCES)
We are grateful to the following colleagues for the clinical images they have given us for this book and also for granting us permission to use figures from their published works:
Steve Ahing, DDS
Faculty of Dentistry, University of Manitoba, Winnipeg, Manitoba, Canada
Figure 19-20F
Franco Antoniazzi, MD
Department of Pediatrics, University of Verona, Verona, Italy
Figure 20-4
Dean Barringer and Marnie Danzinger
Figure 6-7
†Volker Becker, MD
Pathologisches Institut der Universität, Erlangen, Germany
Figures 7-18 and 7-21
J.V. Been, MD
Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands
Figure 10-7C
Beryl Benacerraf, MD
Diagnostic Ultrasound Associates, P.C., Boston, Massachusetts, USA
Figures 13-29A, 13-35A, and 13-37A
Kunwar Bhatnagar, MD
Department of Anatomical Sciences and Neurobiology, School of Medicine University of Louisville, Louisville, Kentucky, USA
Figures 9-33, 9-34, and 19-10
†Deceased.
David Bolender, MD
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Figure 14-14BC
Dr. Mario João Branco Ferreira
Servico de Dermatologia, Hospital de Desterro, Lisbon, Portugal
Figure 19-5A
Albert E. Chudley, MD, FRCPC, FCCMG
Department of Pediatrics and Child Health, Section of Genetics and Metabolism, Children’s Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
Manitoba Institute of Cell Biology, Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Figure 17-2
Vassilios Fanos, MD Department of Pediatrics, University of Verona, Verona, Italy
Figure 20-4
João Carlos Fernandes Rodrigues, MD Servico de Dermatologia, Hospital de Desterro, Lisbon, Portugal
Figure 19-5B
Frank Gaillard, MB, BS, MMed Department of Radiology, Royal Melbourne Hospital, Australia
Figures 4-15 and 9-19B
Gary Geddes, MD
Lake Oswego, Oregon, USA
Figure 14-14A
Barry H. Grayson, MD, and Bruno L. Vendittelli, MD
New York University Medical Center, Institute of Reconstructive Plastic Surgery, New York, New York, USA
Figure 9-40
Christopher R. Harman, MD, FRCSC, FACOG Department of Obstetrics, Gynecology, and Reproductive Sciences, Women’s Hospital and University of Maryland, Baltimore, Maryland, USA
Figures 7-17 and 12-23
†Jean Hay, MSc Department of Anatomy, University of Manitoba, Winnipeg, Manitoba, Canada
Figure 17-25
Blair Henderson, MD Department of Radiology, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada
Figure 13-6
Lyndon M. Hill, MD
Magee-Women’s Hospital, Pittsburgh, Pennsylvania, USA
Figures 11-7 and 12-14
†Klaus V. Hinrichsen, MD
Medizinische Fakultät, Institut für Anatomie, Ruhr-Universität Bochum, Bochum, Germany
Figures 5-12A, 9-2, and 9-26
Dr. Jon and Mrs. Margaret Jackson
Figure 6-9B
†Deceased.
Evelyn Jain, MD, FCFP
Breastfeeding Clinic, Calgary, Alberta, Canada
Figure 9-24
John A. Jane, Sr., MD
David D. Weaver Professor of Neurosurgery, Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
Figure 14-12
Robert Jordan, MD
St. George’s University Medical School, True Blue, Grenada
Figures 6-6B and 7-25
Linda J. Juretschke, MD
Ronald McDonald Children’s Hospital, Loyola University Medical Center, Maywood, Illinois, USA
Figure 7-31
Dagmar K. Kalousek, MD
Department of Pathology, University of British Columbia, Children’s Hospital, Vancouver, British Columbia, Canada
Figures 8-11AB, 11-14A, 12-12C, 12-16, and 20-6AB
E.C. Klatt, MD
Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, Georgia, USA
Figure 7-16
Wesley Lee, MD
Division of Fetal Imaging, William Beaumont Hospital, Royal Oak, Michigan, USA
Figures 13-20 and 13-30A
Deborah Levine, MD, FACR
Departments of Radiology and Obstetric & Gynecologic Ultrasound, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Figures 6-8, 6-15, 8-10, 9-43CD, 17-35B, and cover image (magnetic resonance image of 27-week fetus)
E.A. (Ted) Lyons, OC, MD, FRCPC, FACR
Departments of Radiology, Obstetrics & Gynecology, and Human Anatomy & Cell Science, Division of Ultrasound, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada
In Vitro Fertilization Program, Toronto Hospital, Toronto, Ontario, Canada
Figure 2-17A
Preface
We have entered an era of achievement in the fields of molecular biology, genetics, and clinical embryology, perhaps like no other. The sequencing of the human genome has been achieved and several mammalian species, as well as the human embryo, have been cloned. Scientists have created and isolated human embryonic stem cells, and their use in treating certain intractable diseases continues to generate widespread debate. These remarkable scientific developments have already provided promising directions for research in human embryology, which will have an impact on medical practice in the future.
The 10th edition of The Developing Human has been thoroughly revised to reflect current understanding of some of the molecular events that guide development of the embryo. This book also contains more clinically oriented material than previous editions; these sections are set as blue boxes to differentiate them from the rest of the text. In addition to focusing on clinically relevant aspects of embryology, we have revised the Clinically Oriented Problems with brief answers and added more case studies online that emphasize the importance of embryology in modern medical practice.
This edition follows the official international list of embryologic terms (Terminologia Embryologica, Georg Thieme Verlag, 2013). It is important that physicians and scientists throughout the world use the same name for each structure.
This edition includes numerous new color photographs of embryos (normal and abnormal). Many of the illustrations have been improved using three-dimensional renderings and more effective use of colors. There are also many new diagnostic images (ultrasound and magnetic resonance image) of embryos and fetuses to illustrate their three-dimensional aspects. An innovative set of 18 animations that will help students understand the complexities of embryologic development now comes with this book. When one of the animations is especially relevant to a passage in the text, the icon has been added in the margin. Maximized animations are available to teachers who have adopted The Developing Human for their lectures (consult your Elsevier representative).
The coverage of teratology (studies concerned with birth defects) has been increased because the study of abnormal development of embryos and fetuses is helpful in understanding risk estimation, the causes of birth defects, and how malformations may be prevented. Recent advances in the molecular aspects of developmental biology have been highlighted (in italics) throughout the book, especially in those areas that appear promising for clinical medicine or have the potential for making a significant impact on the direction of future research.
We have continued our attempts to provide an easy-to-read account of human development before birth and during the neonatal period (1 to 28 days). Every chapter has been thoroughly reviewed and revised to reflect new findings in research and their clinical significance.
The chapters are organized to present a systematic and logical approach to embryo development. The first chapter introduces readers to the scope and importance of embryology,
the historical background of the discipline, and the terms used to describe the stages of development. The next four chapters cover embryonic development, beginning with the formation of gametes and ending with the formation of basic organs and systems. The development of specific organs and systems is then described in a systematic manner, followed by chapters dealing with the highlights of the fetal period, the placenta and fetal membranes, the causes of human birth defects, and common signaling pathways used during development. At the end of each chapter there are summaries of key features, which provide a convenient means of ongoing review. There are also references that contain both classic works and recent research publications.
Keith L. Moore
T.V.N. (Vid) Persaud
Mark G. Torchia
Acknowledgments
The Developing Human is widely used by medical, dental, and many other students in the health sciences. The suggestions, constructive criticisms, and comments we received from instructors and students around the world have helped us improve this 10th edition.
When learning embryology, the illustrations are an essential feature to facilitate both understanding of the subject and retention of the material. Many figures have been improved, and newer clinical images replace older ones.
We are indebted to the following colleagues (listed alphabetically) for either critical reviewing of chapters, making suggestions for improvement of this book, or providing some of the new figures: Dr. Steve Ahing, Faculty of Dentistry, University of Manitoba, Winnipeg; Dr. Albert Chudley, Departments of Pediatrics & Child Health and Biochemistry & Medical Genetics, University of Manitoba, Winnipeg; Dr. Blaine M. Cleghorn, Faculty of Dentistry, Dalhousie University, Halifax, Nova Scotia; Dr. Frank Gaillard, Radiopaedia.org, Toronto, Ontario; Dr. Ray Gasser, Faculty of Medicine, Louisiana State University Medical Center, New Orleans; Dr. Boris Kablar, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia; Dr. Sylvia Kogan, Department of Ophthalmology, University of Manitoba, Winnipeg, Manitoba; Dr. Peeyush Lala, Faculty of Medicine, Western University, Ontario, London, Ontario; Dr. Deborah Levine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Dr. Marios Loukas, St. George’s University, Grenada; Dr. Stuart Morrison, Department of Radiology, Cleveland Clinic, Cleveland, Ohio; Professor Bernard J. Moxham, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales; Dr. Michael Narvey, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba; Dr. Drew Noden, Department of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, New York; Dr. Shannon Perry, School of Nursing, San Francisco State University, California; Dr. Gregory Reid, Department of Obstetrics, Gynecology,
and Reproductive Sciences, University of Manitoba, Winnipeg; Dr. L. Ross, Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas; Dr. J. Elliott Scott, Departments of Oral Biology and Human Anatomy & Cell Science, University of Manitoba, Winnipeg; Dr. Brad Smith, University of Michigan, Ann Arbor, Michigan; Dr. Gerald S. Smyser, formerly of the Altru Health System, Grand Forks, North Dakota; Dr. Richard Shane Tubbs, Children’s Hospital, Birmingham, Alabama; Dr. Ed Uthman, Clinical Pathologist, Houston/Richmond, Texas; and Dr. Michael Wiley, Division of Anatomy, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario. The new illustrations were prepared by Hans Neuhart, President of the Electronic Illustrators Group in Fountain Hills, Arizona.
The stunning collection of animations of developing embryos was produced in collaboration with Dr. David L. Bolender, Associate Professor, Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin. We would like to thank him for his efforts in design and in-depth review, as well as his invaluable advice. Our special thanks go to Ms. Carol Emery for skillfully coordinating the project.
At Elsevier, we are indebted to Ms. Meghan K. Ziegler, Content Strategist, for her continued interest and encouragement, and we are especially thankful to Ms. Kelly McGowan, Content Development Specialist, for her invaluable insights and many helpful suggestions. Their unstinting support during the preparation of this new edition was greatly appreciated. Finally, we should also like to thank Ms. Kristine Feeherty, Project Manager; Ms. Maggie Reid, Designer; Ms. Amy Naylor, Art Buyer; and Ms. Thapasya Ramkumar, Multimedia Producer, at Elsevier for nurturing this book to completion. This new edition of The Developing Human is the result of their dedication and technical expertise.
Keith L. Moore
T.V.N. (Vid) Persaud
Mark G. Torchia
1 Introduction to Human Development 1
Developmental Periods 1
Stages of Emb ryonic Dev elopment 2
Postnatal Per iod 2
Infancy 2
Childhood 2
Puberty 2
Adulthood 4
Significance of Embryology 4
Historical Gleanings 4
Ancient Views of Hum an Emb ryology 4
Embryology in the Mid dle Age s 5
The Renaissance 5
Genetics and Human Development 7
Molecular Biology of Human Development 7
Human Biokinetic Embryology 8
Descriptive Terms in Embryology 8
Clinically Oriented Problems 8
2 First Week of Human Development 11
Gametogenesis 11
Meiosis 12
Spermatogenesis 12
Oogenesis 17
Prenatal Mat uration of Ooc ytes 17
Postnatal Mat uration of Ooc ytes 17
Comparison of Gametes 17
Uterus, Uterine Tubes, and Ovaries 18
Uterus 18
Uterine Tubes 18
Ovaries 18
Female Reproductive Cycles 20
Ovarian Cycle 20
Follicular Dev elopment 21
Ovulation 22
Corpus Luteum 22
Menstrual Cycle 23
Phases of Men strual Cyc le 24
Transportation of Gametes 25
Oocyte Transport 25
Sperm Transport 25
Maturation of Sperms 26
Viability of Gametes 26
Sequence of Fertilization 27
Phases of Fer tilization 29
Fertilization 29
Cleavage of Zygote 30
Formation of Blastocyst 33
Summary of First Week 35
Clinically Oriented Problems 36
3 Second Week of Human Development 39
Completion of Implantation of Blastocyst 39
Formation of Amniotic Cavity, Embryonic Disc, and Umbilical Vesicle 41
Development of Chorionic Sac 42
Implantation Sites of Blastocysts 46
Summary of Implantation 46
Summary of Second Week 48
Clinically Oriented Problems 49
4 Third Week of Human Development 51
Gastrulation: Formation of Germ Layers 51
Primitive Streak 52
Fate of Primitive Str eak 54
Notochordal Process and Notochord 54
Allantois 58
Neurulation: Formation of Neural Tube 58
Neural Plate and Neu ral Tub e 59
Neural Crest For mation 59
Development of Somites 61
Development of Intraembryonic Coelom 62
Early Development of Cardiovascular System 62
Vasculogenesis and Ang iogenesis 62
Primordial Car diovascular Sys tem 62
Development of Chorionic Villi 63
Summary of Third Week 64
Clinically Oriented Problems 67
5 Fourth to Eighth Weeks of Human Development 69
Phases of Embryonic Development 69
Folding of Embryo 70
Folding of Emb ryo in the Med ian Plane 70
Folding of Emb ryo in the Hor izontal Plane 70
Germ Layer Derivatives 70
Control of Embryonic Development 72
Highlights of Fourth to Eighth Weeks 74
Fourth Week 74
Fifth Week 75
Sixth Week 78
Seventh Wee k 78
Eighth Week 84
Estimation of Embryonic Age 85
Summary of Fourth to Eighth Weeks 87
Clinically Oriented Problems 88
6 Fetal Period: Ninth Week to Birth 91
Estimation of Fetal Age 93
Trimesters of Pre gnancy 93
Measurements and Cha racteristics of Fetuses 93
Highlights of Fetal Period 94
Nine to Twelve Wee ks 94
Thirteen to Six teen Wee ks 95
Seventeen to Twe nty Wee ks 95
Twenty-One to Twe nty-Five Wee ks 96
Twenty-Six to Twe nty-Nine Wee ks 97
Thirty to Thirty-Four Wee ks 97
Thirty-Five to Thi rty-Eight Wee ks 97
Expected Date of Delivery 99
Factors Influencing Fetal Growth 99
Cigarette Smo king 99
Multiple Pregnancy 99
Alcohol and Ill icit Dru gs 99
Impaired Ute roplacental and Fetoplacental Blo od Flo w 99
Genetic Factors and Gro wth Retardation 100
Procedures for Assessing Fetal Status 100
Ultrasonography 100
Diagnostic Amn iocentesis 100
Alpha-Fetoprotein Ass ay 101
Spectrophotometric Stu dies 101
Chorionic Vil lus Sam pling 101
Cell Cultures and Chr omosomal Analysis 102
Noninvasive Pre natal Dia gnosis 102
Fetal Transfusion 103
Fetoscopy 103
Percutaneous Umb ilical Cor d Blo od Sampling 103
Magnetic Res onance Ima ging 103
Fetal Monitoring 103
Summary of Fetal Period 103
Clinically Oriented Problems 104
7 Placenta and Fetal Membranes 107
Placenta 107
Decidua 109
Development of Pla centa 109
Placental Cir culation 111
Placental Mem brane 113
Functions of Pla centa 114
Placental End ocrine Syn thesis and Secretion 117
The Placenta as an All ograft 117
The Placenta as an Inv asive Tum or-like
Structure 118
Uterine Growth dur ing Pre gnancy 118
Parturition 119
Stages of Lab or 119
Placenta and Fet al Mem branes aft er Birth 121
Maternal Sur face of Pla centa 121
Fetal Surface of Pla centa 121
Umbilical Cor d 124
Amnion and Amn iotic Flu id 126
Umbilical Vesicle 129
Significance of Umb ilical Ves icle 130
Fate of Umbilical Ves icle 130
Allantois 130
Multiple Pregnancies 130
Twins and Fet al Mem branes 130
Dizygotic Twi ns 131
Monozygotic Twi ns 132
Other Types of Mul tiple Bir ths 133
Summary of Placenta and Fetal
Membranes 135
Neonatal Period 138
Clinically Oriented Problems 138
8 Body Cavities, Mesenteries, and Diaphragm 141
Embryonic Body Cavity 141
Mesenteries 144
Division of Emb ryonic Bod y Cav ity 144
Development of Diaphragm 146
Septum Transversum 147
Pleuroperitoneal Mem branes 147
Dorsal Mesentery of Eso phagus 147
Muscular Ingrowth fro m Lat eral Bod y Walls 148
Positional Cha nges and Inn ervation of Diaphragm 148
Summary of Development of Body Cavities, Mesenteries, and Diaphragm 151
Clinically Oriented Problems 153
9
Pharyngeal Apparatus, Face, and Neck 155
Pharyngeal Arches 155
Pharyngeal Arc h Com ponents 157
Pharyngeal Pouches 161
Derivatives of Pha ryngeal Pouches 161
Pharyngeal Grooves 164
Pharyngeal Membranes 164
Development of Thyroid Gland 168
Histogenesis of Thy roid Gla nd 169
Development of Tongue 172
Lingual Papillae and Tas te Bud s 172
Nerve Supply of Ton gue 173
Development of Salivary Glands 174
Development of Face 174
Development of Nasal Cavities 181
Paranasal Sin uses 181
Development of Palate 182
Primary Palate 182
Secondary Pal ate 182
Summary of Pharyngeal Apparatus, Face, and Neck 191
Clinically Oriented Problems 191
10 Respiratory System 195
Respiratory Primordium 195
Development of Larynx 196
Development of Trachea 198
Development of Bronchi and Lungs 200
Maturation of Lun gs 201
Summary of Respiratory System 206
Clinically Oriented Problems 207
11 Alimentary System 209
Foregut 210
Development of Eso phagus 210
Development of Sto mach 211
Omental Bur sa 211
Development of Duo denum 214
Development of Liv er and Bil iary Apparatus 217
Development of Pan creas 219
Development of Spl een 221
Midgut 221
Herniation of Mid gut Loo p 223
Rotation of Mid gut Loo p 224
Retraction of Int estinal Loo ps 224
Cecum and App endix 225
Hindgut 233
Cloaca 233
Anal Canal 233
Summary of Alimentary System 234
Clinically Oriented Problems 239
12 Urogenital System 241
Development of Urinary System 243
Development of Kid neys and Ureters 243
Development of Uri nary Bla dder 255
Development of Ure thra 258
Development of Suprarenal Glands 259
Development of Genital System 260
Development of Gon ads 260
Development of Gen ital Duc ts 262
Development of Mal e Gen ital Duc ts and Glands 264
Development of Fem ale Gen ital Duc ts and Glands 264
Development of Vag ina 266
Development of External
Genitalia 267
Development of Mal e Ext ernal
Genitalia 267
Development of Fem ale Ext ernal
Genitalia 268
Development of Inguinal Canals 276
Relocation of Testes and Ovaries 278
Testicular Des cent 278
Ovarian Descent 278
Summary of Urogenital System 278
Clinically Oriented Problems 280
13 Cardiovascular System
283
Early Development of Heart and Blood Vessels 284
Development of Vei ns Ass ociated wit h
Embryonic Hea rt 285
Fate of Vitelline and Umb ilical
Arteries 288
Later Development of Heart 289
Circulation thr ough Pri mordial Heart 291
Partitioning of Pri mordial Hea rt 293
Changes in Sin us Ven osus 294
Conducting Sys tem of Hea rt 301
Birth Defects of Heart and Great Vessels 301
Derivatives of Pharyngeal Arch
Arteries 317
Derivatives of Fir st Pai r of Pha ryngeal
Arch Arteries 317
Derivatives of Sec ond Pai r of Pha ryngeal
Arch Arteries 317
Derivatives of Thi rd Pai r of Pha ryngeal
Arch Arteries 318
Derivatives of Fou rth Pai r of Pha ryngeal
Arch Arteries 318
Fate of Fifth Pai r of Pha ryngeal Arc h
Arteries 320
Derivatives of Six th Pai r of Pha ryngeal
Arch Arteries 320
Pharyngeal Arc h Art erial Bir th
Defects 320
Fetal and Neonatal Circulation 325
Fetal Circulation 325
Transitional Neo natal Cir culation 325
Derivatives of Fet al Ves sels and Structures 329
Development of Lymphatic System 331
Development of Lym ph Sac s and Lymphatic Duc ts 331
Development of Tho racic Duc t 331
Development of Lym ph Nod es 331
Development of Lym phocytes 331
Development of Spl een and Tonsils 332
Summary of Cardiovascular System 332
Clinically Oriented Problems 334
14 Skeletal System 337
Development of Bone and Cartilage 337
Histogenesis of Car tilage 339
Histogenesis of Bon e 339
Intramembranous Oss ification 339
Endochondral Oss ification 340
Development of Joints 341
Fibrous Joints 342
Cartilaginous Joi nts 342
Synovial Joints 342
Development of Axial Skeleton 342
Development of Ver tebral Column 342
Development of Rib s 344
Development of Ste rnum 344
Development of Cra nium 344
Cranium of Neo nate 346
Postnatal Gro wth of Cra nium 347
Development of Appendicular Skeleton 349
Summary of Skeletal System 353
Clinically Oriented Problems 353
15 Muscular System 355
Development of Skeletal Muscle 355
Myotomes 357
Pharyngeal Arc h Mus cles 358
Ocular Muscles 358
Tongue Muscles 358
Limb Muscles 358
16
Development of Smooth Muscle 358
Development of Cardiac Muscle 359
Summary of Muscular System 361
Clinically Oriented Problems 361
Development of Limbs 363
Early Stages of Limb Development 363
Final Stages of Limb Development 367
Cutaneous Inn ervation of Lim bs 367
Blood Supply of Lim bs 371
Birth Defects of Limbs 372
Summary of Limb Development 377
Clinically Oriented Problems 377
17 Nervous System 379
Development of Nervous System 379
Development of Spinal Cord 382
Development of Spi nal Gan glia 384
Development of Spi nal Men inges 385
Positional Cha nges of Spi nal
Cord 387
Myelination of Ner ve Fib ers 387
Development of Brain 392
Brain Flexures 392
Hindbrain 392
Choroid Plexuses and Cer ebrospinal
Fluid 396
Midbrain 396
Forebrain 396
Birth Defects of Brain 403
Development of Peripheral Nervous System 412
Spinal Nerves 412
Cranial Nerves 412
Development of Autonomic Nervous System 414
Sympathetic Ner vous Sys tem 414
Parasympathetic Ner vous Sys tem 414
Summary of Nervous System 414
Clinically Oriented Problems 415
18 Development of Eyes and Ears 417
Development of Eyes and Related
Structures 417
Retina 419
Ciliary Body 423
Iris 423
Lens 425
Aqueous Cha mbers 426
Cornea 427
Choroid and Scl era 427
Eyelids 427
Lacrimal Gla nds 428
Development of Ears 428
Internal Ears 428
Middle Ears 430
External Ears 431
Summary of Eye Development 434
Summary of Ear Development 435
Clinically Oriented Problems 435
19 Integumentary System 437
Development of Skin and Appendages 437
Epidermis 437
Dermis 439
Glands 440
Hairs 445
Nails 446
Teeth 446
Summary of Integumentary System 454
Clinically Oriented Problems 454
20 Human Birth Defects 457
Classification of Birth Defects 457
Teratology: Study of Abnormal Development 458
Birth Defects Caused by Genetic Factors 458
Numeric Chr omosomal Abnormalities 459
Structural Chr omosomal Abnormalities 466
Birth Defects Cau sed by Mut ant Genes 469
Developmental Sig naling Pathways 471
Birth Defects Caused by Environmental Factors 472
Principles of Ter atogenesis 472
Critical Periods of Hum an Development 472
Human Teratogens 475
Birth Defects Caused by Multifactorial Inheritance 484
Summary of Birth Defects 484
Clinically Oriented Problems 485
21 Common Signaling Pathways Used
During Development 487
Intercellular Communication 488
Gap Junctions 488
Cell Adhesion Mol ecules 489
Morphogens 490
Retinoic Acid 490
Transforming Gro wth Fac tor- β and Bone
Morphogenetic Pro teins 490
Hedgehog 491
WNT/ β -Catenin Pathway 492
Protein Kinases 493
Receptor Tyr osine Kin ases 493
Hippo Signaling Pat hway 494
Notch-Delta Pathway 494
Transcription Factors 496
HOX Proteins 496
PAX Genes 496
Basic Helix-Loop-Helix Tra nscription Factors 497
Epigenetics 497
Histones 498
Histone Methylation 498
DNA Methylation 498
MicroRNAs 499
Stem Cells: Differentiation versus Pluripotency 499
Summary of Common Signaling Pathways
Used During Development 500
Appendix 503
Index 513
CHAPTER
1
Introduction to Human Development
Developmental Periods 1
Stages of Embryonic Development 2
Postnatal Period 2
Infancy 2
Childhood 2
Puberty 2
Adulthood 4
Significance of Embryology 4
Historical Gleanings 4
Ancient Views of Human Embryology 4
Embryology in the Middle Ages 5
The Renaissance 5
Genetics and Human Development 7 Molecular Biology of Human Development 7
Human Biokinetic Embryology 8
Descriptive Terms in Embryology 8
Clinically Oriented Problems 8
uman development is a continuous process that begins when an oocyte (ovum) from a female is fertilized by a sperm (spermatozoon) from a male (Fig. 1-1). Cell division, cell migration, programmed cell death (apoptosis), differentiation, growth, and cell rearrangement transform the fertilized oocyte, a highly specialized, totipotent cell, a zygote, into a multicellular human being. Most changes occur during the embryonic and fetal periods; however, important changes occur during later periods of development: neonatal period (first 4 weeks), infancy (first year), childhood (2 years to puberty), and adolescence (11 to 19 years). Development does not stop at birth; other changes, in addition to growth, occur after birth (e.g., development of teeth and female breasts).
DEVELOPMENTAL PERIODS
It is customary to divide human development into prenatal (before birth) and postnatal (after birth) periods. The development of a human from fertilization of an oocyte to birth is divided into two main periods, embryonic and fetal. The main changes that occur prenatally are illustrated in the Timetable of Human Prenatal Development (see Fig. 1-1). Examination of the timetable reveals that the most visible advances occur during the third to eighth weeks— the embryonic period. During the fetal period, differentiation and growth of tissues and organs occur and the rate of body growth increases.
Stages of Embryonic Development
Early development is described in stages because of the variable period it takes for embryos to develop certain morphologic characteristics. Stage 1 begins at fertilization and embryonic development ends at stage 23, which occurs on day 56 (see Fig. 1-1). A trimester is a period of 3 months, one third of the 9-month period of gestation. The most critical stages of development occur during the first trimester (13 weeks), when embryonic and early fetal development is occurring.
Postnatal Period
This is the period occurring after birth. Explanations of frequently used developmental terms and periods follow.
Infancy
This is the period of extrauterine life, roughly the first year after birth. An infant age 1 month or younger is called a neonate. Transition from intrauterine to
extrauterine existence requires many critical changes, especially in the cardiovascular and respiratory systems. If neonates survive the first crucial hours after birth, their chances of living are usually good. The body grows rapidly during infancy; total length increases by approximately one half and weight is usually tripled. By 1 year of age, most infants have six to eight teeth.
Childhood
This is the period between infancy and puberty. The primary (deciduous) teeth continue to appear and are later replaced by the secondary (permanent) teeth. During early childhood, there is active ossification (formation of bone), but as the child becomes older, the rate of body growth slows down. Just before puberty, however, growth accelerates—the prepubertal growth spurt.
Puberty
This is the period when humans become functionally capable of procreation (reproduction). Reproduction is
FIGURE 1–1
Early stages of development. Development of an ovarian follicle containing an oocyte, ovulation, and the phases of the menstrual cycle are illustrated. Human development begins at fertilization, approximately 14 days after the onset of the last normal menstrual period. Cleavage of the zygote in the uterine tube, implantation of the blastocyst in the endometrium (lining) of the uterus, and early development of the embryo are also shown. The alternative term for the umbilical vesicle is the yolk sac; this is an inappropriate term because the human vesicle does not contain yolk.
Neural
Scrotum
the process by which organisms produce children. In females, the first signs of puberty may be after age 8; in males, puberty commonly begins at age 9.
Adulthood
Attainment of full growth and maturity is generally reached between the ages of 18 and 21 years. Ossification and growth are virtually completed during early adulthood (21 to 25 years).
SIGNIFICANCE OF EMBRYOLOGY
Clinically oriented embryology refers to the study of embryos; the term generally means prenatal development of embryos, fetuses, and neonates (infants aged 1 month and younger). Developmental anatomy refers to the structural changes of a human from fertilization to adulthood; it includes embryology, fetology, and postnatal development. Teratology is the division of embryology and pathology that deals with abnormal development (birth defects). This branch of embryology is concerned with various genetic and/or environmental factors that disturb normal development and produce birth defects (see Chapter 20).
Clinically oriented embryology:
● Bridges the gap between prenatal development and obstetrics, perinatal medicine, pediatrics, and clinical anatomy
● Develops knowledge concerning the beginnings of life and the changes occurring during prenatal development
● Builds an understanding of the causes of variations in human structure
● Illuminates clinically oriented anatomy and explains how normal and abnormal relations develop
● Supports the research and application of stem cells for treatment of certain chronic diseases
Knowledge that physicians have of normal development and the causes of birth defects is necessary for giving the embryo and fetus the best possible chance of developing normally. Much of the modern practice of obstetrics involves applied embryology. Embryologic topics of special interest to obstetricians are oocyte and sperm transport, ovulation, fertilization, implantation, fetal-maternal relations, fetal circulation, critical periods of development, and causes of birth defects.
In addition to caring for the mother, physicians guard the health of the embryo and fetus. The significance of embryology is readily apparent to pediatricians because some of their patients have birth defects resulting from maldevelopment, such as diaphragmatic hernia, spina bifida cystica, and congenital heart disease.
Birth defects cause most deaths during infancy. Knowledge of the development of structure and function is essential for understanding the physiologic changes that occur during the neonatal period (first 4 weeks) and for helping fetuses and neonates in distress. Progress in surgery, especially in the fetal, perinatal, and pediatric age groups, has made knowledge of human development even more clinically significant. Surgical treatment of fetuses is
now possible in some situations. The understanding and correction of most defects depend on knowledge of normal development and the deviations that may occur. An understanding of common congenital birth defects and their causes also enables physicians, nurses, and other health-care providers to explain the developmental basis of birth defects, often dispelling parental guilt feelings. Health-care professionals who are aware of common birth defects and their embryologic basis approach unusual situations with confidence rather than surprise. For example, when it is realized that the renal artery represents only one of several vessels originally supplying the embryonic kidney, the frequent variations in the number and arrangement of renal vessels are understandable and not unexpected.
HISTORICAL GLEANINGS
If I have seen further, it is by standing on the shoulders of giants.
– Sir Isaac Newton, English mathematician, 1643–1727
This statement, made more than 300 years ago, emphasizes that each new study of a problem rests on a base of knowledge established by earlier investigators. The theories of every age offer explanations based on the knowledge and experience of investigators of the period. Although we should not consider them final, we should appreciate rather than scorn their ideas. People have always been interested in knowing how they developed and were born and why some embryos and fetuses develop abnormally. Ancient people developed many answers to the reasons for these birth defects.
Ancient Views of Human Embryology
Egyptians of the Old Kingdom, approximately 3000 BC, knew of methods for incubating birds’ eggs, but they left no records. Akhnaton (Amenophis IV) praised the sun god Aton as the creator of the germ in a woman, maker of the seed in man, and giver of life to the son in the body of his mother. The ancient Egyptians believed that the soul entered the infant at birth through the placenta.
A brief Sanskrit treatise on ancient Indian embryology is thought to have been written in 1416 BC. This scripture of the Hindus, called Garbha Upanishad, describes ancient views concerning the embryo. It states:
From the conjugation of blood and semen (seed), the embryo comes into existence. During the period favorable for conception, after the sexual intercourse, (it) becomes a Kalada (one-day-old embryo). After remaining seven nights, it becomes a vesicle. After a fortnight it becomes a spherical mass. After a month it becomes a firm mass. After two months the head is formed. After three months the limb regions appear.
Greek scholars made many important contributions to the science of embryology. The first recorded embryologic studies are in the books of Hippocrates of Cos, the famous Greek physician (circa 460–377 BC), who is regarded as the father of medicine. In order to understand how the human embryo develops, he recommended:
