Development Of The Human Zygote Essay Research

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Development of the Human Zygote

November 16, 1995

Hundreds of thousands of times a year a single-celled zygote, smaller

than a grain of sand, transforms into an amazingly complex network of cells, a

newborn infant. Through cellular differentiation and growth, this process is

completed with precision time and time again, but very rarely a mistake in the

“blueprint” of growth and development does occur. Following is a description of

how the pathways of this intricate web are followed and the mistakes which

happen when they are not.

The impressive process of differentiation changes a single-cell into a

complicated system of cells as distinct as bold and bone. Although embryonic

development takes approximately nine months, the greatest amount of cellular

differentiation takes place during the first eight weeks of pregnancy. This

period is called embryogenesis.

During the first week after fertilization, which takes place in the

Fallopian tube, the embryo starts to cleave once every twenty-four hours (Fig.

1). Until the eight or sixteen cell stage, the individual cells, or blastomeres,

are thought to have the potential to form any part of the fetus (Leese, Conaghan,

Martin, and Hardy, April 1993). As the blastomeres continue to divide, a solid

ball of cells develops to form the morula (Fig. 1). The accumulation of fluid

inside the morula, transforms it into a hollow sphere called a blastula, which

implants itself into the inner lining of the uterus, the endometrium (Fig. 1).

The inner mass of the blastula will produce the embryo, while the outer layer of

cells will form the trophoblast, which eventually will provide nourishment to

the ovum (Pritchard, MacDonald, and Gant, 1985).

Figure 1:Implantation process and development during

embryogenesis (Pritchard, MacDonald and

Gant, 1985)

During the second week of development, gastrulation, the process by

which the germ layers are formed, begins to occur. The inner cell mass, now

called the embryonic disc, differentiates into a thick plate of ectoderm and an

underlying layer of endoderm. This cellular multiplication in the embryonic

disc marks the beginning of a thickening in the midline that is called the

primitive streak. Cells spread out laterally from the primitive streak between

the ectoderm and the endoderm to form the mesoderm. These three germ layers,

which are the origins of many structures as shown in Table 1, begin to develop.

Table 1: Normal Germ Layer Origin of Structures in Some or all Vertebrates

(Harrison, 1969)

Normal Germ Layer Origin of Structures in Some or All Vertebrates

EctodermMesodermEndoderm Skin epidermis

Hair Feathers Scales Beaks Nails Claws Sebaceous, sweat, and

mammary glands Oral and anal lining tooth enamel Nasal epithelium Lens of

the eye Inner earBrainSpinal cordRetina and other eye partsNerve cells and

gangliaPigment cellsCanal of external earmedulla of the adrenal glandPituitary

gland Dermis of the skinConnective tissueMusclesSkeletal componentsOuter

coverings of the eyeCardiovascular system Heart Blood cells Blood

vesselsKidneys and excretory ductsGonads and reproductive ductsCortex of the

adrenal glandSpleenLining of coelomic cavitiesMesenteries LiverGall

bladderPancreasThyroid glandThymus glandParathyroid glandsPalatine tonsilsMiddle

earEustachian tubeUrinary bladderPrimordial germ cellsLining of all organs of

digestive tract and respiratory tract

During the third week of development, the cephalic (head) and caudal

(tail) end of the embryo become distinguishable. Most of the substance of the

early embryo will enter into the formation of the head. Blood vessels begin to

develop in the mesoderm and a primitive heart may also be observed (Harrison,

1969). Cells rapidly spread away from the primitive streak to eventually form

the neural groove, which will form a tube to the gut. When the neural folds

develop on either side of the groove, the underlying mesoderm forms segmentally

arranged blocks of mesoderm called somite. These give rise to the dermis of the

skin, most skeletal muscles, and precursors of vertebral bodies. the otocyst,

which later becomes the inner ear, and the lens placodes, which later form the

lenses of the adult eyes, are derived from the ectoderm.

The strand of cardiovascular functioning is apparent during the fourth

week. The heart shows early signs of different chambers and begins to pump

blood through the embryo which simultaneously has well developed its kidneys,

thyroid gland, stomach, pancreas, lungs, esophagus, gall bladder, larynx, nd

trachea (Carlson, 1981).

Several new structures are observed, organs continue developing, and

some previously formed structures reorganize during the fifth week of

embryogenesis. The cranial and spinal nerves begin to form and the cerebral

hemispheres and the cerebellum are visible. The spleen, parathyroid glands,

thymus gland, retina, and gonads, all new structures, also begin to form. The

gastrointestimer tract undergoes considerable development as the middle part of

the primitive intestine becomes a loop larger than the abdominal cavity. Next,

it must then project into the umbilical cord until there is room for the entire

bowel. Finally, the heart develops walls or atrial and ventricular septa and

atriventricle cushion. These cushions thicken the junction of the atrium and

ventricle. the atrial and ventricular septa meanwhile divide their respective

chambers into right and left halves (Harrison, 1969).

The sixth week is characterized by the completion of most organ

formation. The embryo has a more identifiable human face with basic structure

of the eyes and ears now developed. Hard and soft palates appear, the salivary

glands begin to form, and there is an early differentiation of the cells that

later develop into the teeth. Division of the heart is essentially completed

and the valves begin to form. The primitive intestinal tract is divided into

the anterior and posterior chambers that will later develop into the urinary

bladder and the rectum, respectively. At the end of the week, the gonads are

histologically recognizable as either testes or ovaries (Pritchard, MacDonald,

and Gant, 1985).

The embryo looks similar to miniature human when it enters the seventh

week of embryogenesis. During this last week, the pituitary gland takes a

definitive structure, the eyelids become visible, the last group of muscles

begin to form, and bone marrow appears for the first time. the main concerns of

this period are the different developments taking place in the male and female.

This is first shown as the M?llerian ducts degenerate in males, but continues to

develop in females, where they will later differentiate to become the Fallopian

tubes, the uterus and the inner part of the vagina. The Wolffian ducts

degenerate in female embryos, but continue to develop into the ductus deferens

in the male. Although the external genitalia continue to grow and develop, they

are still unable to be visibly identified as male or female. By the end of this

week the placenta begins to take on definite characteristics, and for the first

time blood from the maternal circulation enters the placental circulation

(Carlson,1981).

After this period of embryogenesis the embryo is given the name fetus.

The remainder of pregnancy is primarily concerned with growth and cellular

differentiation, but during this period of growth, mistakes which can cause

birth defects are still highly effective, as they were in the first seven weeks

of development. What are some of these defects which begin during the first

trimester of pregnancy and how are they caused?

Obviously the process of a developing embryo and fetus is very

complicated and although most of the babies born each year are free from any

abnormalities, up to five percent of all newborn infants have congenital

anomalies, birth defects (Cunningham, MacDonald, and Gant, July/August 1989).

Seventy percent of birth defects are unknown spontaneous errors of development.

Of the thirty percent which are known, twenty-five percent are associated with

genetic factors that include major chromosomal defect and point mutations, three

percent with venereal diseases such as syphilis and rubella, and two percent

with teratogens, medications and drugs (Cunningham, MacDonald, and Gant,

Feb./March 1991).

Spontaneous errors in development, whose causes are unknown, can happen

in the central nervous system, face, gut, genitourinary system, and heart as

shown in Table 2. The time during pregnancy which these may occur is also is

also shown in Table 2 and ranges from twenty-three days to twelve weeks, all

which fall into the first trimester. How these anomalies are triggered in birth

defects is unknown. Neural Tube Defects, which causes are also unknown, are

some of the most common defects and result in infant mortality or serious

disability. These abnormalities include anencephaly, a malformation

characterized by cerebral hemispheres that are absent, and spina bifida, an

exposed , ruptured spine (Medicine, March 1993).

TABLE 2. Relative timing and development of pathology of certain birth defects

(Adapted from Cunningham, MacDonald and Gant, February/ March 1991).

Birth defects by area

Central Nervous System Closure of anterior neural tube Closure in a portion of

posterior neural tube26 days28 days Face Closure of lip Fusion of maxillary

palatal shelves resolution of branchial cleft36 days10 weeks8 weeks Gut

Lateral septation of foregut into trachea Lateral septation of cloaca into

rectum and urogenital sinus Recanalization of duodenum Rotation of

intestinal loop Return of midgut from yolk sac to abdomen Obliteration of

vitelline duct Closure of pleuroperitoneal canal30 days6 weeks7 to 8

weeks10 weeks10 weeks10 weeks6 weeks Genitourinary system Migration of

infraumbilical mesenchyme Fusion of lower portion of M?llerian ducts Fusion of

urethral folds (labia minora)30 days10 weeks12 weeks Heart Directional

development of bulbous cordis septum ventricular septum closure34 days6

weeks Limb Genesis of radial bone Separation of digital rays38 days6 weeks

Complex Prechordal mesoderm development Development of posterior axis

23 days23 days

On the other hand the effects and consequences of teratogens are known.

“A teratogen is any agent such as a medication or other systemically absorbed

chemical or factor like hyperthermia, that produces permanent abnormal embryonic

physical development or physiology (Cunningham, MacDonald, and Gant, Feb./March

1991). The embryonic period is most critical with respect to malformations

because it encompasses organogenesis. Drugs and chemicals such as alcohol and

organic mercury can cause mental retardation, while infection such as varicella,

the chicken pox, can cause limb defects, neurologic anomalies, and skin scars

(Baker, April 1990). A more complete list of drugs, chemicals and infections,

and their effects are listed in Table 3. These type of birth defects are unique

because abnormalities due to drugs and chemical exposure are potentially

preventable (Cunningham, MacDonald, and Gant, Feb./March 1991).

TABLE 3. Effects and comments of documented teratogens (ACOG Technical

Bulletin, Feb.1985)

AgentEffectsComments

Drugs and Chemicals

Alcohol Growth retardation, mental retardation, various major and minor

malformations Risk due to ingestion of one or two drinks per day (1-2 oz) may

cause a small reduction in average birth weight. AndrogensHermaphroditism

in female offspring, advanced genital development in males Effects are dose

dependent and related to stage of embryonic development. Depending on time of

exposure, clitoral enlargement or labioscrotal fusion can be produced.

AnticoagulantsHypoplastic nose, bony abnormalities, broad short hands with

shortened phalanges, intrauterine growth retardation, deformations of neck,

central nervous system defectsRisk for a seriously affected child is

considered to be 25% when anticoagulants that inhibit vitamin K are used in the

first trimester. Antithyroid drugsfetal goiterGoiter in fetus may lead

to malpresentation with hyperextended head. Diethylstilbestrol (DES)Vaginal

adenosis, abnormalities of cervix and uterus in females, possible infertility in

males and femalesVaginal adenosis is detected in over 50% of women whose

mothers took these drugs before the ninth week of pregnancy. Lead

Increased abortion rate and stillbirthsCentral nervous system

development of the fetus may be adversely affected. LithiumCongenital heart

diseaseHeart malfunctions due to first trimester exposure occur in

approximately 2%. Organic mercuryMental retardation, spasticity, seizures,

blindnessExposed individuals include consumers of contaminated grain and

fish. Contamination is usually with methyl mercury Isotrtinoin (Accutane)

Increased abortion rate, nervous system defects, cardiovascular effects,

craniofacial dysmorphism, cleft palateFirst trimester exposure may result in

approximately 25% anomaly rate ThalidomideBilateral limb deficiencies-days

27-40, anotia and microtia-days 21-27, other abnormalitiesOf children

whose mothers used thalidomide, 20% show the effect. TrimethadioneCleft

lip or cleft palate, cardiac defects, growth retardation, mental retardation

Risks for defects or spontaneous abortion is 60-80% with first trimester

exposure. Valproic acidNeural tube defectsExposure must be prior

to normal closure of neural tube during first trimester to get open defect.

Infections

RubellaCataracts, deafness, heart lesions, plus expanded syndrome

including effects on all organsMalformation rate is 50% if mother is

infected during first trimester. Varicellapossible effects on all organs

including skin scarring and muscle atrophyZoster immune globulin is

available for newborns exposed during last few days of gestation.

Chromosomal abnormalities, the leading cause of birth defects, develop

during meiotic division in the gonad, the organ which produces sex cells. A

chromosome may drop out of the dividing cell and thus be lost. Fertilization of

this type of gamete results in a zygote with a missing chromosome. If the

gamete fails to split equally at meiotic division and the cell with the extra

chromosome is fertilized, the zygote becomes trisomic (Pritchard, MacDonald, and

Gant, 1985). Down Syndrome, the most common chromosomal defect, results from an

extra chromosome (trisomy 21). Less common is chromosomal translocation defect.

Translocation is the transfer of a segment of one chromosome to a different site

on the same chromosome or to a different chromosome (Pritchard, MacDonald, and

Gant, 1985). Many other syndromes, their chromosomal complement, and signs of

these syndromes which are recognizable at birth are shown in Table 4.

TABLE 4. Findings in established chromosomal abnormalities in man

(Pritchard, MacDonald, and Gant, 1985)

SyndromeChromosomal ComplementSigns

Recognizable at Birth Turners45 / XLymphangiectatic edema of hands

and feet Klinefelters47 / XXYNone Triple X47 / XXXNone

YY47None Downs trisomy 2147Mongoloid facies, Simian line

Translocation46Same Trisomy 13 – 1547Cleft palate, Harelip,

Eye defects, Polydactyly Trisomy 16 – 1847Finger flexion, Lowest

ears, Digital arches Cat cry46 (Deletion B 5)Cat cry, Moon face

During the first trimester of prgnancy, an embryo must correctly make

its way through a complex matrix of differentiation and development to become a

normal infant. When something does go wrong, the embryo or fetus will

unfortunately have some type of defect. The amazing accuracy with which a

single cell can become something as complex as a newborn infant is a truley

incredible feat!

Works Cited

Baker, David A. “Danger of Varicella-Zoster Virus Infection.” Contemporary

OB/GYN April 1990: 52.

Carlson, Bruce M. Patten’s Foundations of Embryology. McGraw-Hill Inc. 1981.

Cunningham, MacDonald, and Gant. Williams Obstetrics, Supplement no. 10. 18th

ed, Prentice-Hall, Inc. Februay/March 1991: 2,3.

“Folic Acid for the Prevetion of Recurrent Neural Tube Defect.” Medicine March

1993.

Harrison, Ross G. Organization and Develpment of the Embryo. Yale University

Press. 1969.

Leese, Conaghan, Martin, and Hardy. “Early Human Embryo Metabolism.” Bio

Essays vol. 15, No. 4 April 1993: 259.

Pritchard, MacDonald, and Gant. Williams Obstetrics. 17th ed, Prentice-Hall,

Inc. 1985: 139-142, 800.

Pritchard, MacDonald, and Gant. Williams Obstetrics, Supplement no. 13. 17th

ed, Prentice-Hall, Inc. July/August 1987: 2.

“Teratology.” ACOG Technical Bulletin February 1985.