Introduction to Human 1 Development
DEVELOPMENTAL PERIODS, 1 Embryology in the Middle Ages, 4 Stages of Embryonic Development, 1 The Renaissance, 5 Postnatal Period, 1 GENETICS AND HUMAN DEVELOPMENT, 6 Infancy, 1 MOLECULAR BIOLOGY OF HUMAN Childhood, 1 DEVELOPMENT, 7 Puberty, 1 DESCRIPTIVE TERMS IN EMBRYOLOGY, 7 Adulthood, 2 CLINICALLY ORIENTED PROBLEMS, 9 SIGNIFICANCE OF EMBRYOLOGY, 2 HISTORICAL GLEANINGS, 4 Ancient Views of Human Embryology, 4
Human development is a continuous process that begins weeks), when embryonic and early fetal development is when an oocyte (ovum) from a female is fertilized by a sperm occurring. (spermatozoon) from a male to form a single-celled zygote (Fig. 1.1). Cell division, cell migration, programmed cell POSTNATAL PERIOD death (apoptosis), differentiation, growth, and cell rearrange- ment transform the fertilized oocyte, a highly specialized, This is the period occurring after birth. Explanations of totipotent cell, the zygote, into a multicellular human being. frequently used postnatal developmental terms and periods Most developmental changes occur during the embryonic follow. and fetal periods; however, important changes occur during later periods of development: the neonatal period (first 4 INFANCY weeks), infancy (first year), childhood (2 years to puberty), and adolescence (11 to 19 years). Infancy is the period of extrauterine life, roughly the first year after birth. An infant age 1 month or younger is called a neonate (newborn). The transition from intrauterine to DEVELOPMENTAL PERIODS extrauterine existence requires many critical changes, especially in the cardiovascular and respiratory systems. If It is customary to divide human development into prenatal neonates survive the first crucial hours after birth, their (before birth) and postnatal (after birth) periods. The devel- chances of living are usually good. The body grows rapidly opment of a human from a zygote to birth is divided into two during infancy; total length increases by approximately one main periods, embryonic and fetal. The main changes that half, and weight is usually tripled. By 1 year of age, most occur prenatally are illustrated in the Timetable of Human infants have six to eight teeth. Prenatal Development (see Fig. 1.1). Examination of the timetable reveals that the most visible advances occur during CHILDHOOD the third to eighth weeks—the embryonic period. During the fetal period, differentiation and growth of tissues and This is the period between infancy and puberty. The primary organs occur, and the rate of body growth increases. (deciduous) teeth continue to appear and are later replaced by the secondary (permanent) teeth. During early childhood, STAGES OF EMBRYONIC DEVELOPMENT there is active ossification (formation of bone), but as the child becomes older, the rate of body growth slows down. Early development is described in stages because of the Just before puberty, however, growth accelerates—the pre- variable period it takes for embryos to develop certain pubertal growth spurt. morphologic characteristics. Stage 1 begins at fertilization, and embryonic development ends at stage 23, which occurs PUBERTY 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 Puberty is the period when humans become functionally stages of development occur during the first trimester (13 capable of procreation (reproduction). In females, the first
1 2 THE DEVELOPING HUMAN signs of puberty may be after age 8; in males, puberty com- with abnormal development (birth defects). This branch of monly begins at age 9. embryology is concerned with various genetic and/or envi- ronmental factors that disturb normal development and ADULTHOOD produce birth defects (see Chapter 20). Clinically oriented embryology: Attainment of full growth and maturity is generally reached between the ages of 18 and 21 years. Ossification and growth • Bridges the gap between prenatal development and are virtually completed during early adulthood (21 to 25 obstetrics, perinatal medicine, pediatrics, and clinical years). Brain development continues into early adulthood, anatomy including changes in gray-matter volume. • Develops knowledge concerning the beginnings of life and the changes occurring during prenatal development • Builds an understanding of the causes of variations in SIGNIFICANCE OF EMBRYOLOGY human structure • Illuminates clinically oriented anatomy and explains how Clinically oriented embryology refers to the study of embryos; normal and abnormal relations develop the term generally means the prenatal development of • Supports the research and application of stem cells for embryos, fetuses, and neonates (infants aged 1 month and the treatment of certain chronic diseases younger). Developmental anatomy refers to the structural changes of a human from fertilization to adulthood; it includes The knowledge that physicians have of normal development embryology, fetology, and postnatal development. Teratology and the causes of birth defects is necessary for giving the is the division of embryology and pathology that deals embryo and fetus the best possible chance of developing
TIMETABLE OF HUMAN PRENATAL DEVELOPMENT 1 TO 10 WEEKS DAYS
Primary follicles Oocyte
EARLY DEVELOPMENT OF OVARIAN FOLLICLE −2
MENSTRUAL PHASE PROLIFERATIVE PHASE Day 1 of last normal menstrual cycle Antrum Mature Oocyte follicle Ovulation
−1 COMPLETION OF DEVELOPMENT OF FOLLICLE
Oocyte Oocyte Ovary CONTINUATION OF PROLIFERATIVE PHASE OF MENSTRUAL CYCLE AGE 1Stage 1 2Stage 2 begins 34Stage 3 begins 56Stage 4 7Stage 5 begins (weeks) Trophoblast Zona pellucida Implantation begins
1
Fertilization Zygote divides MorulaEarly blastocyst Late blastocyst Embryoblast SECRETORY PHASE OF MENSTRUAL CYCLE
8 9 10 Cytotrophoblast 11 Maternal blood 12 Extraembryonic 13 Stage 6 begins 14 Lacunar Connecting stalk Lacunae appear in Amnion Eroded mesoderm syncytiotrophoblast gland network Primary villi Amnion Amniotic cavity 2
Embryonic disc Bilaminar embryonic Primary umbilical disc vesicle Closing plug Embryonic disc Coelom Prechordal plate Fig. 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. CHAPTER 1 — Introduction to Human Development 3
15 16 Stage 7 begins 17 Trilaminar embryo 18 Stage 8 begins 19 20 Stage 9 begins 21 Neural First missed groove menstrual period Amnion Neural plate Neural plate Brain First pairs Neural of somites Primitive groove Neural groove 3 streak Primitive Somite Somite Cut edge streak Arrows indicate of amnion Primitive node migration of Migration of cells from Thyroid gland begins Primitive streak mesenchymal cells primitive streak Length: 1.5 mm Primitive streak to develop 22 Stage 10 begins 23 24 Stage 11 begins 25 26 Stage 12 begins 27 Site of otic pit 28 Stage 13 begins Rostral neuropore Otic (ear) pit 2 pairs of Fore- pharyngeal brain Heart arches Primordia Upper begins of eye limb bud Pharyngeal 4 to beat and ear Heart bulge arches Primitive present Circulatory Rostral Caudal neuropore System Indicates neuropore closes 3 pairs of CRL = crown− Neural folds fusing pharyngeal arches actual size rump length CRL: 5.0 mm 29 30 31 32 Stage 14 begins 33 Stage 15 begins 34 Cerebral vesicles 35 Eye distinct Developing eye Eye Upper limb bud
5 Nasal Hand pit Heart plate Cord Lower Foot Lens pits, optic cups, limb plate CRL: 5.5 mm nasal pits forming Primordial mouth bud CRL: 7.0 mm present CRL: 8.5 mm 36 37 Stage 16 begins 38 39 40 External acoustic 41 Stage 17 begins 42 Large head meatus Ear Eye Digital Ear rays Eye 6 Eye Digital rays Foot- Oral and nasal plate Upper lip and Foot plate cavities confluent nose formed CRL: 9.5 mm CRL: 10.5 mm Ventral view CRL: 12.5 mm AGE (weeks) 43 Actual size 44 Stage 18 begins 45 46 47 Genital tubercle 48 Stage 19 begins 49 Actual size Amniotic sac Wall of uterus Head large but chin Eyelid Urogenital poorly formed. Uterine membrane Grooves between cavity External ear 7 digital rays Anal indicate fingers. membrane Wrist, Eyelids fingers CRL: 13.0 mm forming Smooth and fused CRL: 18 mm chorion 50 Stage 20 begins551 52 Stage 21 begins 3554 Stage 22 begins 556 Stage 23 Genital Ear Upper limbs Eye tubercle Eye Ear longer and bent External genitalia Urethral at elbows. groove Wrist Nose have begun 8 to differentiate. Fingers distinct Fingers Knee but webbed. Anus Elbow Toes Large forehead and Toes CRL: 30 mm 57 58 59 Placenta 60 Genitalia 61 62 Genitalia 63 Phallus Phallus Eye Ear Urogenital Urogenital Beginning fold fold of Wrist 9 fetal Labioscrotal Knee Labioscrotal fold period fold Perineum Perineum Toes Elbow CRL: 45 mm CRL: 50 mm 64 65 66 67 68 69 70 Clitoris Glans of penis Face has a Labium Genitalia have more developed minus or Urethral profile. 10 Urogenital characteristics groove groove but still not Note growth fully formed. of chin Labium Scrotum compared majus to day 44. Ears still positioned lower. CRL: 61 mm Fig. 1.1, cont’d 4 THE DEVELOPING HUMAN normally. Much of the modern practice of obstetrics involves the Hindus, called Garbha Upanishad, describes ancient views applied embryology. Embryologic topics of special interest concerning the embryo. It states: to obstetricians are oocyte and sperm transport, ovulation, fertilization, implantation, fetal-maternal relations, fetal From the conjugation of blood and semen [seed], the embryo circulation, critical periods of development, and causes of comes into existence. During the period favorable for conception, birth defects. after the sexual intercourse, [it] becomes a Kalada [one-day-old In addition to caring for the mother, physicians guard the embryo]. After remaining seven nights, it becomes a vesicle. After health of the embryo and fetus. The significance of embryol- a fortnight it becomes a spherical mass. After a month it becomes ogy is readily apparent to pediatricians because some of their a firm mass. After two months the head is formed. After three patients have birth defects resulting from maldevelopment, months the limb regions appear. such as diaphragmatic hernia, spina bifida cystica, and congenital heart disease. Greek scholars made many important contributions to Birth defects cause most deaths during infancy. Knowledge the science of embryology. The first recorded embryologic of the development of structure and function is essential for studies are in the books of Hippocrates of Cos, the famous understanding the physiologic changes that occur during the Greek physician (circa 460–377 BC), who is regarded as the neonatal period (first 4 weeks) and for helping fetuses and father of medicine. To understand how the human embryo neonates in distress. Progress in surgery, especially in the fetal, develops, he recommended: perinatal, and pediatric age groups, has made knowledge of human development even more clinically significant.Surgi - Take twenty or more eggs and let them be incubated by two or cal treatment of fetuses is now possible in some situations. The more hens. Then each day from the second to that of hatching, understanding and correction of most defects depend on remove an egg, break it, and examine it. You will find exactly as knowledge of normal development and the deviations that I say, for the nature of the bird can be likened to that of man. may occur. An understanding of common congenital birth defects and their causes also enables physicians, nurses, and Aristotle of Stagira (circa 384–322 BC), a Greek philosopher other health-care providers to explain the developmental basis and scientist, wrote a treatise on embryology in which he of birth defects, often dispelling parental feelings of guilt. described the development of the chick and other embryos. Health-care professionals who are aware of common birth Aristotle promoted the idea that the embryo developed from defects and their embryologic basis approach unusual situ- a formless mass, which he described as a “less fully concocted ations with confidence rather than surprise. For example, seed with a nutritive soul and all bodily parts.” This embryo, when it is realized that the renal artery represents only one he thought, arose from menstrual blood after activation by of several vessels originally supplying the embryonic kidney, male semen. the frequent variations in the number and arrangement of Claudius Galen (circa 130–201 AD), a Greek physician renal vessels are understandable and not unexpected. and medical scientist in Rome, wrote a book, On the Formation of the Foetus, in which he described the development and nutrition of fetuses and the structures that we now call the HISTORICAL GLEANINGS allantois, amnion, and placenta. The Talmud contains references to the formation of the If I have seen further, it is by standing on the shoulders of giants. embryo. The Jewish physician Samuel-el-Yehudi, who lived —SIR ISAAC NEWTON, ENGLISH MATHEMATICIAN, 1643–1727 during the second century AD, described six stages in the formation of the embryo, from a “formless, rolled-up thing” This statement, made more than 300 years ago, emphasizes to a “child whose months have been completed.” Talmud that each new study of a problem rests on a base of knowledge scholars believed that the bones and tendons, the nails, the established by earlier investigators. The theories of every age marrow in the head, and the white of the eyes were derived offer explanations based on the knowledge and experience from the father, “who sows the white,” but the skin, flesh, of investigators of the period. Although we should not consider blood, and hair were derived from the mother, “who sows them final, we should appreciate rather than scorn their the red.” These views were according to the teachings of ideas. People have always been interested in knowing how both Aristotle and Galen. they developed and were born and why some embryos and fetuses develop abnormally. Ancient people developed many EMBRYOLOGY IN THE MIDDLE AGES answers to the reasons for these birth defects. The growth of science was slow during the medieval period, ANCIENT VIEWS OF HUMAN EMBRYOLOGY but a few high points of embryologic investigation undertaken during this time are known to us. It is cited in the Quran Egyptians of the Old Kingdom, approximately 3000 BC, knew (seventh century AD), the holy book of Islam, that human of methods for incubating birds’ eggs. Akhnaton (Amenophis beings are produced from a mixture of secretions from the IV) praised the sun god Aton as the creator of the germ in male and female. Several references are made to the creation a woman, maker of the seed in man, and giver of life to of a human being from a nutfa (“small drop”). Reference is the son in the body of his mother. The ancient Egyptians made to the leech-like appearance of the early embryo. Later believed that the soul entered the infant at birth through the embryo is said to resemble a “chewed substance.” the placenta. Constantinus Africanus of Salerno (circa 1020–1087 AD) A brief Sanskrit treatise on ancient Indian embryology is wrote a concise treatise entitled De Humana Natura. Africanus thought to have been written in 1416 BC. This scripture of described the composition and sequential development of CHAPTER 1 — Introduction to Human Development 5 the embryo in relation to the planets and each month during many new observations. He also studied the development of pregnancy, a concept unknown in antiquity. Medieval scholars the fallow deer; however, when unable to observe early hardly deviated from the theory of Aristotle, which stated developmental stages, he concluded that embryos were that the embryo was derived from menstrual blood and semen. secreted by the uterus. Girolamo Fabricius (1537–1619) wrote Because of a lack of knowledge, drawings of the fetus in the two major embryologic treatises, including one entitled De uterus often showed a fully developed infant frolicking in Formato Foetu (The Formed Fetus), which contained many the womb (Fig. 1.2). illustrations of embryos and fetuses at different stages of development. THE RENAISSANCE Early microscopes were simple, but they opened an exciting new field of observation. In 1672, Regnier de Graaf observed Leonardo da Vinci (1452–1519) made accurate drawings of small chambers in the rabbit’s uterus and concluded that dissections of pregnant uteri containing fetuses (Fig. 1.3). they could not have been secreted by the uterus. He stated He introduced the quantitative approach to embryology by that they must have come from organs that he called ovaries. making measurements of prenatal growth. Undoubtedly, the small chambers that de Graaf described It has been stated that the embryologic revolution began were blastocysts (see Fig. 1.1). He also described follicles, with the publication of William Harvey’s book De Generatione which were called graafian follicles; they are now called Animalium in 1651. Harvey believed that the male seed or vesicular ovarian follicles. sperm, after entering the womb or uterus, became metamor- Marcello Malpighi, studying what he believed were unfertil- phosed into an egg-like substance from which the embryo ized hen’s eggs in 1675, observed early chick embryos. As a developed. Harvey (1578–1657) was greatly influenced by result, he thought the egg contained a miniature chick. A one of his professors at the University of Padua, Fabricius young medical student in Leiden, Johan Ham van Arnhem, of Acquapendente, an Italian anatomist and embryologist and his countryman Anton van Leeuwenhoek, using an who was the first to study embryos from different species of animals. improved microscope in 1677, first observed human sperm. Harvey examined chick embryos with simple lenses and made However, they misunderstood the sperm’s role in fertilization. They thought the sperm contained a miniature preformed human being that enlarged when it was deposited in the female genital tract (Fig. 1.4). Caspar Friedrich Wolff refuted both versions of the pre- formation theory in 1759, after observing that parts of the embryo develop from “globules” (small spherical bodies). He examined unincubated eggs but could not see the embryos described by Malpighi. He proposed the layer concept, whereby division of what we call the zygote produces layers of cells (now called the embryonic disc) from which the AB embryo develops. His ideas formed the basis of the theory of epigenesis, which states that “development results from growth and differentiation of specialized cells.” These
CDE
FG
Fig. 1.2 A–G, Illustrations from Jacob Rueff’s De Conceptu et Generatione Hominis (1554) showing the fetus developing from a coagulum of blood and semen in the uterus. This theory was based on the teachings of Aristotle, and it survived until the late 18th century. (From Needham J: A history of embryology, ed 2, Cambridge, United Fig. 1.3 Reproduction of Leonardo da Vinci’s drawing made in the Kingdom, 1934, Cambridge University Press; with permission of Cambridge 15th century showing a fetus in a uterus that has been incised and University Press, England.) opened. 6 THE DEVELOPING HUMAN
body is composed of cells and cell products. The cell theory soon led to the realization that the embryo developed from a single cell, the zygote, which underwent many cell divisions as the tissues and organs formed. Wilhelm His (1831–1904), a Swiss anatomist and embryolo- gist, developed improved techniques for fixation, sectioning, and staining of tissues and for reconstruction of embryos. His method of graphic reconstruction paved the way for the current production of three-dimensional, stereoscopic, and computer-generated images of embryos. Franklin P. Mall (1862–1917), inspired by the work of Wilhelm His, began to collect human embryos for scientific study. Mall’s collection forms a part of the Carnegie Collection of embryos that is known throughout the world. It is now in the National Museum of Health and Medicine in the Armed Forces Institute of Pathology in Washington, DC. Wilhelm Roux (1850–1924) pioneered analytic experimen- tal studies on the physiology of development in amphibia, which was pursued further by Hans Spemann (1869–1941). For his discovery of the phenomenon of primary induction— how one tissue determines the fate of another—Spemann Fig. 1.4 Copy of a 17th-century drawing of a sperm by Hartsoeker. received the Nobel Prize in 1935. Over the decades, scientists The miniature human being within it was thought to enlarge after the have been isolating the substances that are transmitted from sperm entered an ovum. Other embryologists at this time thought the one tissue to another, causing induction. oocyte contained a miniature human being that enlarged when it was Robert G. Edwards (1925–2013) and Patrick Steptoe stimulated by a sperm. (1913–1988) pioneered one of the most revolutionary develop- ments in the history of human reproduction: the technique of in vitro fertilization. These studies resulted in the birth important discoveries first appeared in Wolff’s doctoral dis- of Louise Brown, the first test“ tube baby,” in 1978. Since sertation Theoria Generationis. He also observed embryonic then, many millions of couples throughout the world, who masses of tissue that partly contribute to the development were considered infertile, have experienced the birth of their of the urinary and genital systems—wolffian bodies and children because of this new reproductive technology. Edwards wolffian ducts—now called the mesonephros and mesonephric was awarded the 2010 Nobel Prize in Physiology and Medicine ducts, respectively (see Chapter 12). for the development of in vitro fertilization. The preformation controversy ended in 1775 when Lazzaro John Gurdon (1933–)and Shinya Yamanaka (1962–) were Spallanzani showed that both the oocyte and sperm were awarded the 2012 Nobel Prize in Physiology and Medicine necessary for initiating the development of a new individual. for the discovery that mature cells can be reprogrammed to From his experiments, including artificial insemination in become pluripotent. Gurdon and Yamanaka showed that dogs, he concluded that the sperm was the fertilizing agent the genome can be conserved during differentiation and that initiated the developmental processes. Heinrich Christian can be reprogrammed to an immature stage. Their discovery Pander discovered the three germ layers of the embryo, which led to a better understanding of development and paved the he named the blastoderm. He reported this discovery in way for therapeutic cloning and the use of stem cells in 1817 in his doctoral dissertation. treating specific clinical conditions. Etienne Saint Hilaire and his son, Isidore Saint Hilaire, made the first significant studies of abnormal development in 1818. They performed experiments in animals that were GENETICS AND HUMAN DEVELOPMENT designed to produce birth defects, initiating what we now know as the science of teratology. In 1859, Charles Darwin (1809–1882), an English biologist Karl Ernst von Baer described the oocyte in the ovarian and evolutionist, published his book On the Origin of Species, follicle of a dog in 1827, approximately 150 years after the in which he emphasized the hereditary nature of variability discovery of sperm. He also observed cleaving zygotes in the among members of a species as an important factor in evolu- uterine tube and blastocysts in the uterus. He contributed tion. Gregor Mendel, an Austrian monk, developed the new knowledge about the origin of tissues and organs from principles of heredity in 1865, but medical scientists and the layers described earlier by Malpighi and Pander. Von biologists did not understand the significance of these Baer formulated two important embryologic concepts, namely, principles in the study of mammalian development for many that there are distinct stages of embryonic development and years. that general characteristics precede specific ones. His sig- Walter Flemming observed chromosomes in 1878 and nificant and far-reaching contributions resulted in his being suggested their probable role in fertilization. In 1883, Edouard regarded as the father of modern embryology. van Beneden observed that mature germ cells have a reduced Matthias Schleiden and Theodor Schwann were responsible number of chromosomes. He also described some features for great advances being made in embryology when they of meiosis, the process whereby the chromosome number formulated the cell theory in 1839. This concept stated that the is reduced in germ cells. CHAPTER 1 — Introduction to Human Development 7
Walter Sutton (1877–1916) and Theodor Boveri (1862–1915) declared independently in 1902 that the behavior of chro- MOLECULAR BIOLOGY OF HUMAN mosomes during germ cell formation and fertilization agreed DEVELOPMENT with Mendel’s principles of inheritance. In the same year, Garrod reported alcaptonuria (a genetic disorder of Rapid advances in the field of molecular biology have led phenylalanine-tyrosine metabolism) as the first example of to the application of sophisticated techniques (e.g., recom- mendelian inheritance in human beings. Many geneticists binant DNA technology, genomic sequencing, RNA genomic consider Sir Archibald Garrod (1857–1936) the father of medical hybridization, chimeric models, transgenic mice, stem cell genetics. It was soon realized that the zygote contains all the manipulation, and gene therapy). These techniques are now genetic information necessary for directing the development widely used in research laboratories to address such diverse of a new human being. problems as the genetic regulation of morphogenesis, the Felix von Winiwarter reported the first observations on temporal and regional expression of specific genes, and how human chromosomes in 1912, stating that there were 47 cells are committed to form the various parts of the embryo. chromosomes in body cells. Theophilus Shickel Painter For the first time, we are beginning to understand how, when, concluded in 1923 that 48 was the correct number, a conclu- and where selected genes are activated and expressed in the sion that was widely accepted until 1956, when Joe Hin Tjio embryo during normal and abnormal development (see and Albert Levan reported finding only 46 chromosomes in Chapter 21). embryonic cells. The first mammal, a sheep namedDolly , was cloned in James Watson and Francis Crick deciphered the molecular 1997 by Ian Wilmut and his colleagues using the technique structure of DNA in 1953, and in 2000, the human genome of somatic cell nuclear transfer. Since then, other animals was sequenced. The biochemical nature of the genes on the have been successfully cloned from cultured differentiated 46 human chromosomes has been decoded. Chromosome adult cells. Interest in human cloning has generated consider- studies were soon used in medicine in a number of ways, able debate because of its social, ethical, and legal implica- including clinical diagnosis, chromosome mapping, and tions. Moreover, there is concern that cloning may result in prenatal diagnosis. neonates with birth defects and serious diseases. Once the normal chromosomal pattern was firmly estab- Human embryonic stem cells are pluripotential, capable of lished, it soon became evident that some persons with self-renewal and able to differentiate into specialized cell congenital birth defects had an abnormal number of chro- types, including artificial gametes. The isolation and repro- mosomes. A new era in medical genetics resulted from the grammed culture of human embryonic stem cells hold great demonstration by Jérôme Jean Louis Marie Lejeune and potential for the treatment of chronic diseases, including associates in 1959 that infants with Down syndrome (trisomy spinal cord injuries, age-related macular degeneration, 21) have 47 chromosomes instead of the usual 46 in their amyotrophic lateral sclerosis, Alzheimer disease, and Parkinson body cells. It is now known that chromosomal aberrations disease as well as other degenerative, malignant, and genetic are a significant cause of birth defects and embryonic death disorders (see the National Institutes of Health web page (see Chapter 20). “Stem Cell Information” [2016]). In 1941, Sir Norman Gregg reported an “unusual number of cases of cataracts” and other birth defects in infants whose mothers had contracted rubella (caused by the rubella virus) DESCRIPTIVE TERMS IN EMBRYOLOGY in early pregnancy. For the first time, concrete evidence was presented showing that the development of the human The English equivalents of the standard Latin forms of terms embryo could be adversely affected by an environmental are given in some cases, such as sperm (spermatozoon). The factor. Twenty years later, Widukind Lenz and William McBride Federative International Committee on Anatomical Terminol- reported rare limb deficiencies and other severe birth defects, ogy does not recommend the use of eponyms (words derived induced by the sedative thalidomide, in the infants of mothers from someone’s name), but they are commonly used clinically; who had ingested the drug. The thalidomide tragedy alerted hence, they appear in parentheses, such as uterine tube (fallopian the public and health-care providers to the potential hazards tube). In anatomy and embryology, several terms relating to of drugs, chemicals, and other environmental factors during position and direction are used, and reference is made to pregnancy (see Chapter 20). various planes of the body. All descriptions of the adult are Sex chromatin was discovered in 1949 by Dr. Murray Barr based on the assumption that the body is erect, with the and his graduate student Ewart (Mike) Bertram at Western upper limbs by the sides and the palms directed anteriorly University in London, Ontario, Canada. Their research (Fig. 1.5A). This is the anatomical position. revealed that the nuclei of nerve cells of female cats had The terms anterior or ventral and posterior or dorsal are used sex chromatin and that male cats did not. The next step to describe the front or back of the body or limbs and the was to determine whether a similar phenomenon existed relations of structures within the body to one another. When in human neurons. Keith L. Moore, who joined Dr. Barr’s describing embryos, the terms ventral and dorsal are used research group in 1950, discovered that sex chromatin (see Fig. 1.5B). Superior and inferior are used to indicate the patterns existed in the somatic cells of humans and many relative levels of different structures (see Fig. 1.5A). For representatives of the animal kingdom. He also developed embryos, the terms cranial (or rostral) and caudal are used a buccal smear sex chromatin test. This research forms the to denote relationships to the head and caudal eminence basis of several modern techniques currently used world- (tail), respectively (see Fig. 1.5B). Distances from the center wide for the screening and diagnosis of human genetic of the body or the source or attachment of a structure are conditions. designated as proximal (nearest) or distal (farthest). In the 8 THE DEVELOPING HUMAN
Superior
Cranial
Dorsal Anterior Posterior
Ventral
Caudal Inferior A B
Sagittal plane
Lateral
CDE Median section Transverse section Frontal (coronal) section Fig. 1.5 Drawings illustrating descriptive terms of position, direction, and planes of the body. A, Lateral view of an adult in the anatomical position. B, Lateral view of a 5-week embryo. C and D, Ventral views of a 6-week embryo. E, Lateral view of a 7-week embryo. In describing development, it is necessary to use words denoting the position of one part to another or to the body as a whole. For example, the vertebral column (spine) develops in the dorsal part of the embryo, and the sternum (breastbone) develops in the ventral part of the embryo.
lower limb, for example, the knee is proximal to the ankle sagittal plane is any vertical plane passing through the body and distal to the hip. that is parallel to the median plane (see Fig. 1.5C). A frontal The median plane is an imaginary vertical plane of section (coronal) plane is any vertical plane that intersects the median that passes longitudinally through the body. Median sections plane at a right angle (see Fig. 1.5E) and divides the body into divide the body into right and left halves (see Fig. 1.5C). The anterior or ventral and posterior or dorsal parts. A transverse terms lateral and medial refer to structures that are, respectively, (axial) plane refers to any plane that is at right angles to both farther from or nearer to the median plane of the body. A the median and coronal planes (see Fig. 1.5D). CHAPTER 1 — Introduction to Human Development 9
Horder TJ, Witkowski JA, Wylie CC, editors: A history of embryology, CLINICALLY ORIENTED PROBLEMS Cambridge, United Kingdom, 1986, Cambridge University Press. Jaenisch R: Nuclear cloning and direct reprogramming: the long and the short path to Stockholm, Cell Stem Cell 11:744, 2012. 1. What sequence of events occurs during puberty? Are the Kohl F, von Baer KE: 1792–1876. Zum 200. Geburtstag des “Vaters der events the same in males and females? At what age does Embryologie,” Dtsch Med Wochenschr 117:1976, 1992. presumptive puberty occur in males and females? Meyer AW: The rise of embryology, Stanford, Calif, 1939, Stanford University 2. How do the terms embryology and teratology differ? Press. Moore KL, Persaud TVN, Shiota K: Color atlas of clinical embryology, ed 3. What is the difference between the terms egg, ovum, ovule, 2, Philadelphia, 2000, Saunders. gamete, and oocyte? Murillo-Gonzalés J: Evolution of embryology: a synthesis of classical, experimental, and molecular perspectives, Clin Anat 14:158, 2001. Discussion of these problems appears in the Appendix at Neaves W: The status of the human embryo in various religions, Develop- ment 144:2541, 2017. the back of the book. Needham J: A history of embryology, ed 2, Cambridge, United Kingdom, 1959, Cambridge University Press. Nusslein-Volhard C: Coming to life: how genes drive development, Carlsbad, BIBLIOGRAPHY AND SUGGESTED READING Calif, 2006, Kales Press. Allen GE: Inducers and “organizers”: Hans Spemann and experimental O’Rahilly R: One hundred years of human embryology. In Kalter H, editor: embryology, Hist Philos Life Sci 15:229, 1993. Issues and reviews in teratology, vol 4, New York, 1988, Plenum Press. Blechschmidt E, Gasser RF: Biokinetics and biodynamics of human differ- O’Rahilly R, Müller F: Developmental stages in human embryos, Washington, entiation: principles and applications, Springfield, Ill, 1978, Charles C. DC, 1987, Carnegie Institution of Washington. Thomas. (Republished Berkeley, Calif, 2012, North Atlantic Books.). Persaud TVN, Tubbs RS, Loukas M: A history of human anatomy, ed 2, Churchill FB: The rise of classical descriptive embryology, Dev Biol (N Springfield, Ill, 2014, Charles C. Thomas. Y) 7:1, 1991. Pinto-Correia C: The ovary of Eve: egg and sperm and preformation, Chicago, Craft AM, Johnson M: From stem cells to human development: a distinctly 1997, University of Chicago Press. human perspective on early embryology, cellular differentiation and Slack JMW: Essential developmental biology, ed 3, Hoboken, NJ, 2012, translational research, Development 144:12, 2017. Wiley-Blackwell. Damdimopoulu P, Rodin S, Stenfelt S, et al: Human embryonic stem Smith A: Cell biology: potency unchained, Nature 505:622, 2014. cells, Best Prac Res Clin Obstet Gynaecol 31:2, 2016. Streeter GL: Developmental horizons in human embryos: description of Dunstan GR, editor: The human embryo: Aristotle and the Arabic and European age group XI, 13 to 20 somites, and age group XII, 21 to 29 somites, traditions, Exeter, United Kingdom, 1990, University of Exeter Press. Contrib Embryol Carnegie Inst 30:211, 1942. Gasser R: Atlas of human embryos, Hagerstown, Md, 1975, Harper & Row. Hopwood N: A history of normal plates, tables and stages in vertebrate embryology, Int J Dev Biol 51:1, 2007. CHAPTER 1 — Introduction to Human Development 9.e1
Discussion of Chapter 1 Clinically Oriented Problems