1

Introduction to Human Development

1 Human development begins at fertilization when an oocyte (ovum) from a female is fertilized by a sperm (spermatozoon) from a male and becomes a single-celled zygote. Development involves many changes that transform the zygote into a multicellular human being. Embryology is concerned with the origin and development of a human being from a zygote to birth. The stages of development before birth are shown in Fig. 1.1.

IMPORTANCE OF AND ADVANCES IN EMBRYOLOGY

The study of prenatal stages and mechanisms of human development helps us understand the normal relationships of adult body structures and the causes of birth defects (congenital anomalies). Much of the modern practice of obstetrics involves applied or clinical embryology. Because some children have birth defects, such as spina bifida or congenital heart disease, the significance of embryology is readily apparent to pediatricians. Advances in surgery, especially in procedures involving the prenatal and pediatric age groups, have made knowledge of human development more clinically significant. In addition, as we discover new information about the development processes, we in turn have a better understanding of many diseases and their process, as well as their treatment.

Rapid advances in molecular biology have led to the use of sophisticated techniques (e.g., genomic technology, chimeric models, transgenics, and stem cell manipulation) in research laboratories to explore such diverse issues as the genetic regulation of morphogenesis, the temporal and regional expression of specific genes, and the mechanisms by which cells are committed or differentiate to form the various parts of the embryo. Researchers continue to learn how, when, and where selected genes are activated and expressed in the embryo during normal and abnormal development.

Development begins at fertilization (see Fig. 1.1, first week). The embryonic period covers the first 8 weeks of development of an embryo. The fetal period begins in the ninth week. Examination of the timetable shows that the most externally visible advances occur during the third to eighth weeks.

The critical role of genes, signaling molecules, receptors, and other molecular factors in regulating early embryonic development is rapidly being delineated. In 1995 Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric F. Wieschaus were awarded the Nobel Prize in Physiology or Medicine for their discovery of genes that control embryonic development. Such discoveries are contributing to a better understanding of the causes of spontaneous abortion and birth defects.

Robert G. Edwards (1925–2013) and Patrick Steptoe (1913–1988) pioneered one of the most revolutionary develop-ments in the history of human reproduction: the technique of in vitro fertilization. Their studies resulted in the birth of Louise Brown, the first “test tube baby,” in 1978. Edwards was awarded the Nobel Prize in 2010.

In 1997 Ian Wilmut and colleagues were the first to produce a mammal (a sheep dubbed Dolly) by cloning using the technique of somatic cell nuclear transfer. Since then, other animals have been cloned successfully from cultured differenti-ated adult cells. Interest in human cloning has generated considerable debate because of social, ethical, and legal implications. Moreover, there is concern that cloning may result in an increase in the number of neonates (newborns) with birth defects and serious diseases.

Human embryonic stem cells are pluripotential and capable of developing into diverse cell types. The isolation and culture of human embryonic and other stem cells may hold great promise for the development of molecular therapies.

DESCRIPTIVE TERMS

In anatomy and embryology, specific terms of position, direction, and various planes of the body are used. Descrip-tions of the adult are based on the anatomical position; the body is erect, the upper limbs are at the sides, and the palms are directed anteriorly (Fig. 1.2A). The descriptive terms of position, direction, and planes used for embryos are shown in Fig. 1.2B to E. In describing development, it is necessary to use words denoting the position of one part relative to another or to the body as a whole. For example, the vertebral column develops in the dorsal part of the embryo and the sternum is in the ventral part of the embryo.

2 BEFOREWEAREBORN

Day 1 of last normalmenstrual cycle

Antrum

Oocyte

Primary follicles

Oocyte

OvulationMaturefollicle

Oocyte

Ovary

Oocyte

1 Stage 1

Fertilization Zygote divides Morula Early blastocyst

Zona pellucida

Late blastocyst

Trophoblast

Embryoblast

8

Amniotic cavity

Bilaminar embryonicdisc

Primary umbilicalvesicle

9Lacunae appear insyncytiotrophoblast

10

Closing plug

AmnionCytotrophoblast 11

Eroded gland

Lacunarnetwork

Maternal blood

Embryonic disc Coelom

12 Extraembryonicmesoderm

13 Stage 6 begins

Primary villi

Prechordal plate

Connecting stalk

Embryonic disc

Amnion

14

2 Stage 2 begins 3 4 Stage 3 begins 5 6 Stage 4

Implantation begins

7 Stage 5 begins

EARLY DEVELOPMENT OF OVARIAN FOLLICLE

TIMETABLE OF HUMAN PRENATAL DEVELOPMENT1 TO 10 WEEKS

MENSTRUAL PHASE

AGE(weeks)

1

2

COMPLETION OF DEVELOPMENT OF FOLLICLE

CONTINUATION OF PROLIFERATIVE PHASE OF MENSTRUAL CYCLE

SECRETORY PHASE OF MENSTRUAL CYCLE

PROLIFERATIVE PHASE

DAYS

−1

−2

Fig. 1.1 Early stages of human development. An ovarian follicle containing an oocyte, ovulation, and phases of the menstrual cycle are shown.

CHAPTER1—INTROduCTIONTOHumANdEvElOPmENT 3

7

AGE(weeks)

Head large but chinpoorly formed.

Grooves betweendigital rays

indicate fingers.

Upper limbslonger and bent

at elbows.

Fingers distinctbut webbed.

Beginning of

fetal period

Face has amore developed

profile.

Note growthof chin

comparedto day 44.

External genitaliahave begun

to differentiate.8

9

10

43 44 Stage 18 begins

CRL: 13.0 mm

Actual size

Eyelids forming

Ear

Large forehead

Eye

Nose

Fingers

Toes

50

57

64

58

65

59

66

60

Phallus

Genitalia

Perineum

Clitoris

Labiumminus

Labiummajus

Urogenitalgroove

Ears stillpositioned lower

Labioscrotalfold

Urogenital fold

67

61

68

62

69

63

70

51 52 Stage 21 beginsStage 20 begins 53 55 56 Stage 23

Eye Ear

Elbow

Wrist

Knee

Toes

Eye Ear

Placenta

Elbow

Wrist

Knee

Toes

CRL: 18 mm

Actual size

CRL: 30 mm

CRL: 50 mmCRL: 45 mm

CRL: 61 mm

Amniotic sacGenital tubercle

Urogenitalmembrane

Eyelid

Wrist, fingersfused

External earAnalmembrane

and

Wall of uterus

Uterinecavity

Smoothchorion

45 46 47 Stage 19 begins48 49

orGenitalia have

characteristicsbut still not

fully formed.

Stage 22 begins54

Genitaltubercle

Urethralgroove

Anus

Phallus

Genitalia

Perineum

Labioscrotalfold

Urogenital fold

Glans of penis

Scrotum

Urethralgroove

and

3

4

5

6

Primitive streak

15 16 Stage 7 begins

22 Stage 10 begins

29

36

30

37 Stage 16 begins

Oral and nasalcavities confluent

31

38

32 Stage 14 begins

39

33 Stage 15 begins

40

34

41

35

Cord

42

Eye

Eye

Ear

Stage 17 begins

23 24 Stage 11 begins 25 Stage 12 begins 27 28 Stage 13 begins

Stage 8 begins17 18 19 Stage 9 begins20 21First missed

menstrual period

Arrows indicate migration of mesenchymal cells

Migration of cells fromprimitive streak

Trilaminar embryo

AmnionNeural plate

Primitive streak

Length: 1.5 mm

Neural groove

Neural plate

Somite

Primitive node

Primitive streak

Brain

Neural groove

Somite

Thyroid gland begins to develop

Neural groove

First pairsof somites

Primitivestreak

Heart begins to beat

Neural folds fusing

Rostral neuropore

Primordia of eye and ear present

Caudal neuropore

Heart bulge

Rostral neuropore closes

2 pairs ofpharyngealarches

Otic pit

3 pairs of pharyngeal arches

Upperlimb bud

Indicates actual size

Fore- brain

Pharyngealarches

Site of otic (ear) pit

CRL = crown-rump length CRL: 5.0 mm

CRL: 8.5 mmCRL: 7.0 mm

CRL: 10.5 mm CRL: 12.5 mm

26

CRL: 5.5 mm

CRL: 9.5 mm

Upper lip and nose formed

Eye

Footplate

Digitalrays

Digitalrays

Ventral view

External acousticmeatus

Foot-plate

Eye

Ear

Lens pits, optic cups,nasal pits forming

Developing eye Upper limb bud

Lower limb bud

Heart

Eye

Hand- plate

Cerebral vesiclesdistinct

Foot- platepresent

Nasal pit

Primordial mouth

Large head

Cut edgeof amnion

PrimitiveCirculatorySystem

Fig. 1.1, cont’d

4 BEFOREWEAREBORN

Superior

Inferior

Sagittal plane

Median section Transverse section

Lateral

Anterior

A

C D E

B

Posterior

Cranial

Ventral

Dorsal

Caudal

Frontal (coronal) section

Fig. 1.2 Illustrations of 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. The median plane is an imaginary vertical plane of section that passes longitudinally through the body, dividing it into right and left halves. A sagittal plane refers to any plane parallel to the median plane. A transverse plane refers to any plane that is at right angles to both the median and frontal planes. E, Lateral view of a 7-week embryo. A frontal (coronal) plane is any vertical plane that intersects the median plane at a right angle and divides the body into front (anterior or ventral) and back (posterior or dorsal) parts.

CLINICALLY ORIENTED QUESTIONS

1. Why do we study human embryology? Does it have any practical value in medicine and other health sciences?

2. Physicians date a pregnancy from the first day of the last normal menstrual period, but the embryo does not start

to develop until approximately 2 weeks later (see Fig. 1.1). Why do physicians use this method?

The answers to these questions are at the back of this book.

CHAPTER1—INTROduCTIONTOHumANdEvElOPmENT 4.e1

Answers to Chapter 1 Clinically Oriented Questions