4. Introduction
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Human development is a continuous process that begins
when an oocyte (ovum) from a female is fertilized by a
sperm (spermatozoon) from a male
Cell division, cell migration, proliferation, invagination,
herniation, fusion, fission, programmed cell death,
induction, differentiation, growth, and cell rearrangement
transform the fertilized oocyte, a highly specialized,
totipotent cell (zygote) into a multicellular human being
Although most developmental changes occur during the
embryonic and fetal periods, important changes occur
during later periods of development (infancy, childhood,
adolescence, and early adulthood) such as eruption of
teeth and breast
5. Primordial Germ Cells
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Gametes are derived from Primordial Germ
Cells (PGS) that are formed in the epiblast
during the 2nd week and that move to the wall
of yolk sac
During 4th week, these cells begin to migrate
from the yolk sac to the developing gonads,
where they arrive by the end of 5th week
Mitosis
In preparation for fertilization, germ cells
undergo gametogenesis which includes
meiosis and cytodifferentiation to complete
their maturation
6. Mitosis
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Mitosis is the process whereby one cell
divides, giving rise to two daughter cells that
are genetically identical to the parent cell
Each daughter cell receives the complete
complement of 46 chromosomes
Before a cell enters mitosis, each
chromosome replicates its deoxyribonucleic
acid (DNA)
With the onset of mitosis, the chromosomes
begin to coil, contract, and condense
7.
8. Meiosis
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Meiosis is the cell division that takes place in the germ cells
to generate male and female gametes sperm and egg cells,
respectively
Meiosis requires two cell divisions, meiosis I and meiosis II,
to reduce the number of chromosomes to the haploid
number of 23
As in mitosis, male and female germ cells (spermatocytes
and primary oocytes) at the beginning of meiosis I replicate
their DNA so that each of the 46 chromosomes is duplicated
into sister chromatids
In contrast to mitosis, however, homologous chromosomes
then align themselves in pairs, a process called synapsis
39. How are abnormal gametes
produced?
ideal maternal age for reproduction is generally
considered to be from 18 to 35 years of age
Incidence of chromosomal abnormalities
significantly increases after 35years of age,
such as Turner syndrome (monosomy), Down
syndrome (trisomy) etc. because :
nondisjunction (error in cell division )-during
meiosis homologues chromosomes fail to
separate and move to opposite poles
fresh gene mutation (alterations) increase with
age
40.
41. 1. Down syndrome (Trisomy 21)
Gamete with extra copy of chromosome 21
Characterized by
children with:
Retarded growth
Mental retardation
Upward slanting
eyes (oblique
palpebral fissure)
Flat face with
small ears
Furrowed lower lip
Cardiac defect and
others
42. 2. Edward Syndrome: (Trisomy 18)
Characterized by child with:
Mental deficiency and
growth retardation
Short sternum
prominent occiput
One or more flexed fingers
Absence or hypoplasia of
radus and ulna
Low set ears
Micrognatia and small
mouth
43. 3. Patau syndrome (Trisomy 13)
Mental deficiency; severe
central nervous system
malformations;
sloping forehead;
malformed ears,
scalp defects;
microphthalmia;
bilateral cleft lip and/or
palate;
polydactyly;
posterior prominence of
the heels
44. Turner syndrome (45)
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Turner syndrome in a 14-year-old
girl
Note the classic features of the
syndrome:
short stature,
webbed neck,
absence of sexual
maturation,
broad shieldlike chest with
widely spaced nipples,
lymphedema of the hands
and feet
45. Fertilization
Fertilization is a complex sequence of coordinated
molecular events that begins with contact between
a sperm and an oocyte and ends with the
intermingling of maternal and paternal
chromosomes at metaphase of the first mitotic
division of the zygote
The fertilization process takes approximately 24
hours
Before spermatozoa can fertilize the oocyte, they
must undergo capacitation, during which time a
glycoprotein coat and seminal plasma proteins are
removed from the spermatozoon head in the female
reproductive tracts Fikre B. 45
46. Cont.…
Phase 2: Sperm binding and penetration of the zona
pellucida
Sperm binding occurs through interaction of sperm glycosyl
transferases and ZP3 receptors located on the zona
pellucida
Sperm binding triggers the acrosome reaction, which entails
the fusion of the outer acrosomal membrane and sperm cell
membrane, resulting in the release of acrosomal enzymes
Penetration of the zona pellucida is aided by acrosomal
enzymes, specifically acrosin and hyaluronidases
Sperm contact with the cell membrane of a secondary
oocyte triggers the cortical reaction, which entails the
release of cortical granules (lysosomes) from the oocyte
cytoplasm, which is impermeable to other sperm
Fikre B. 46
47. Cont.…
Phase 3:Fusion of sperm and oocyte cell membranes
occurs with subsequent breakdown of both
membranes at the fusion area
The entire sperm (except the cell membrane) enters
the cytoplasm of the secondary oocyte arrested in
metaphase of meiosis II
The sperm mitochondria and tail degenerate
The sperm nucleus is now called the male pronucleus
Since all sperm mitochondria degenerate, all
mitochondria within the zygote are of maternal origin
(i.e., all mitochondrial DNA are of maternal origin)
Fikre B. 47
48. Fikre B. 48
The secondary oocyte
completes meiosis II,
forming a mature ovum
and second polar body
The nucleus of the mature
ovum is now called the
female pronucleus
Male and female
pronuclei fuse, forming a
zygote(a new cell whose
genotype is an
intermingling of maternal
and paternal
chromosomes)
49. Functions of Fertilization
Stimulates the penetrated oocyte to
complete the second meiotic division.
Restores the normal diploid number of
chromosomes (46) in the zygote
Results in variation of the human species
through mingling of maternal and paternal
chromosomes
Determines chromosomal sex of the embryo (XX/
XY)
Causes metabolic activation of the ootid and
initiates cleavage (cell division) of the zygote
Fikre B. 49
61. Week 3: Gastrulation
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formation three of germ layers
Ectoderm: outside, surrounds other
layers later in development,
generates skin and nervous tissue
Mesoderm: middle layer, generates
most of the muscle, blood and
connective tissues of the body and
placenta
Endoderm: eventually most interior
of embryo, generates the epithelial
lining and associated glands of the
gut, lung, and urogenital tracts
Fikre B. 61
64. What happens if there is “not enough”
gastrulation?
Caudal agenesis (sirenomelia)
Premature regression of the primitive streak leads to widespread loss
of trunk and lower limb mesoderm.
VATeR association:
Vertebral defects
Anal atresia
Tracheo-esophageal
fistula
Renal defects
VACTeRL association:
those above plus…
Cardiovascular defects
Limb (upper) defects
Fikre B. 64
65. If the primitive streak fails to regress, multipotent primitive streak cells can
develop into multi-lineage tumors (containing ecto-, meso-, and endodermal
tissues).
What happens if there is “too much” gastrulation?
Sacrococcygeal teratoma
Fikre B. 65
66. Third to eight weeks: Organogenesis
During the fourth week a flat trilaminar
embryonic disc is folding with the formation of
a cylindrical shape (C) embryo
Folding of the ends of the embryo in the
median plane results in formation of cranial
and caudal regions moving ventrally as the
embryo elongates
Folding of the embryo in the horizontal plane
produces right and left lateral folds
It is due to rapid unproportional growth of
Fikre B. 66
67. Cont.…
By the end of eighth week all the main organ
systems have begin to develop, but function
of most organs is minimal
Because basic organs and systems develop
during this period, exposure to teratogens
(agents that cause abnormal development)
During this period may cause major
congenital malformations
It is the most critical period of development
Fikre B. 67
69. Ninth week to Birth (Fetal period)
Development during the fetal period is primarily concerned
with rapid growth of the body and differentiation of tissue
and organs that started to develop during the embryonic
period
There is a relative slowdown in the growth of the head
compared with that of the rest of the body
Fikre B. 69
70. 9-12th weeks
At the beginning of 9th week head constitute half of
the crown-ramp length of the fetus &the liver is the
major site of erytrhropoiesis
11th week, intestine have returned to the abdomen
Primary ossification centers appear in the skeleton in
the skull and long bones
External genitalia of males and females appear
similar until the end of ninth week, and distinguished
at 12 week and the upper limb reached their final
relative length
Fikre B. 70
71. 13-16th weeks
Growth is very rapid during this period & the
lower limbs have lengthened
In 13th week, slow eye movement occur
By 16 week, the ovaries are differentiated
and have many primordial follicles
containing oogonia
Mother can Feel muscular activity of Fetus
Fikre B. 71
72. 17-20th weeks
Growth slows down
Fetal movements ‘quickening’’ are commonly felt by
the mother
The skin is covered with a greasy cheese-like material
called vernix caseosa
It consists of fatty secretions from fetal sebaceous glands
and dead epidermal cells
It protects the delicate skin from abrasions and hardening
The body of 20-week fetus is usually completely
covered with fine downy hair called lanugo, which help
holding the vernix caseosa on the skin and eyebrows
and head hairs are also visible
Fikre B. 72
73. Cont.…
Brown fat forms during this period
By 18 weeks uterus of female fetus is
completely formed and canalization of
vagina has begun
By 20 weeks the testes of male fetus
begun their descent, but they are still
located on posterior abdominal wall
Fikre B. 73
74. 21-25th Weeks
There is a substantial weight gain
The skin usually wrinkled
At 21 week rapid eye movement begin and
blink-startle responses occur
By 24 week, the secretory epithelial cells or
types II pneumocytes in the inter alveolar
walls of the lung have begun to secrete
surfactant (a surface-active lipid that maintain
the patency of the developing alveoli of the lungs)
&finger nails are also present
Fikre B. 74
75. 26-29th weeks
A fetus may survive if born prematurely and
given intensive care because lungs are
capable of breathing air
Considerable subcutaneous fat has formed
The fetal spleen is now an important site of
hematopoiesis
Erythropoiesis in the spleen ends by 28
weeks, by which the time bone marrow has
become the major site of formation of
erythrocytes
Fikre B. 75
76. 30-34th weeks
Pupillary light reflex can be elicited by 30
weeks
Skin -Pink and smooth & UL &LL have
chubby appearance
Fat in the body is about 8% of the body
weight
32 weeks and above usually survive
Fikre B. 76
77. 35-38th weeks
35 weeks have a firm grasp & exhibit a
spontaneous orientation to light
Fingernails and Toenails are present
fat = 16% of body weight
full term(38 weeks after fertilization or 40 weeks
after LNMP)
skin - white or bluish – pink
chest - prominent
testes - in the scrotum(male)
Fikre B. 77
78. CHILDBIRTH
About 9 Months (about 270 Days) after
Fertilization, at the end of a Full Term
Pregnancy, the Fetus is ready for Birth. By
this time, it has usually moved so that its
Head is against the Cervix
When it is time, A Hormone known as
OXYTOCIN is released from the Pituitary
Gland, that affects a group of large
Involuntary Muscles that surrounds the
Uterus Fikre B. 78
79. Cont.…
WEAK, Irregular Contractions may occur for Several Weeks
before birth (False Labor)
As these Muscles are stimulated, they begin a series of
Rhythmic Contractions knows as LABOR that Expands the
opening of the CERVIX so that it will be large enough (about
10 cm) to allow the baby to pass through it
As contractions continue, they become more Powerful
(PAINFUL) and more Frequent, occurring once every minute
or two
Little by little, in a process (LABOR) that last from 2 to 20
hours, the baby is FORCED toward the Vagina as labor
continues
The Amniotic Sac Breaks (“Breaking Water”), and the fluid it
contains rushes out of the Vagina
Fikre B. 79
80. Cont.…
The baby is finally Forced out of the Uterus and the
Vagina, Head First, still attached to its mother by the
Umbilical Cord
The Baby will begin to cough or cry in order to rid its
lungs of the fluid with which they have been filled
Breathing starts almost immediately
The Umbilical Cord is clamped and cut, leaving a Scar
known as Navel or Belly Button
In the final contractions the Placenta, Amniotic Sac
and the Uterine Lining, collectively called AFTER
BIRTH are expelled from the mother's body about 10
minutes after the baby is born
Fikre B. 80
82. Placenta
The placenta (or afterbirth) is a temporary
fetomaternal organ developed specifically for the
growth and maintenance of a fetus during gestation
At full term, the placenta is discoid with a diameter
of 15 to 25 cm, is approximately 3 cm thick, and
weighs about 500 to 600 g
At birth, it is torn from the uterine wall and,
approximately 30 minutes after birth of the child, is
expelled from the uterine cavity
After birth, when the placenta is viewed from the
maternal side, 15 to 20 slightly bulging areas, the
cotyledons, covered by a thin layer of decidua
basalis, are clearly recognizable
Fikre B. 82
83. Functions of
placenta
1.
2.
3.
4.
5.
6.
Respiratory function
Excretory function
Nutritional function:- placenta transfer nutrients from maternal
circulation to fetus, are Glucose, Lipids, Amino acid and
minerals (fe, ca), Vitamins (folic acid, vit. C), Water and
electrolytes
Endocrine function:- placenta acts as endocrine gland and
secrets:- oestrogen, progesterone, human chorionic
gonadotrophin (HCG), Human placental lactogen (HPL),
thyroid stimulating hormone (TSH), Hormone resembling
adreno-corticotrophine, Relaxin
Barrier function:- prevents transfer of maternal infection. But
some organism can cross like:- mump, measles, rubella, HIV,
syphilis, chicken pox etc.
Enzymatic action- (diamine oxidase that inactivates
circulatory pressue, oxytocinase which neutralizes oxytocin,
Phospholipase A2 which synthesize AA)
Fikre B.
83
85. Multiple pregnancies
In other mammals and man, there is
usually one offspring at a time, however,
multiple births are known
Triplets, quadruplets and other multiple
births may be monozygotic or dizygotic or
both.
Two types of twins:
1. Identical twins (monozygotic twins)
2. Binovular twins (dizygotic twins)
Fikre B. 85
86. 1. Identical twins (monozygotic twins)
During segmentation and the formation of
two cells from a single fertilized ovum,
these two cells may separate and develop in
to two exactly identical twins
They have the same genetic characters;
therefore, they are called “true twins” and
are of the same sex
They have one placenta and a single
chorion
Fikre B. 86
88. 2. Binovular twins (dizygotic twins)
Here two ova are shed during one
ovarian cycle
They become fertilized by two deferent
sperm cells
They may or may not be of the same
sex
They only have family characteristics;
therefore, they are called fraternal twins
Each has its own placenta and chorion
Fikre B. 88
90. Clinical point
Abnormalities may occur
during twinning
Always in monozygotic
twins
These are united twins or
incompletely separated
monozygotic twins
They may be united in
thoracic region
(thoracopagus) or in the
head region (craniopagus)
or through the dorsal or
ventral body surface Fikre B. 90
91. Teratology
Teratology is the science that studies the
causes, mechanisms, and patterns of
abnormal development
Developmental disorders present at birth are
called congenital anomalies, birth defect or
congenital malformation
Fikre B. 91
92. Birth defects
3% of all live-born infants have a major anomaly
Additional anomalies are detected during
postnatal live – about 6% at 2 year-olds, 8% in
5year-olds, other 2% later
Single minor anomalies are present in about
14% of newborns
Major anomalies are more common in early
embryos (up to 15%) than they are in newborns
(3%)
Most severely malformed embryos are
spontaneously aborted during first 6 to 8 weeks
Fikre B. 92
93. Causes of congenital anomalies
1-Genetic factors such as
chromosomal abnormalities and
mutant genes
2-Environmental factors e.g.: the
mother had German measles in early
pregnancy will cause abnormality in
the embryo
3-Combined genetic and
environmental factors
Fikre B. 93
95. Gene mutation: achondroplasia
A boy with achondroplasia
showing:
short stature,
short limbs and fingers,
normal length of trunk,
bowed legs,
a relatively large head,
prominent forehead, and
depressed nasal bridge
Fikre B. 95
96. Adolescent male with
Klinefelter syndrome
(XXY trisomy)
Note the presence of breasts;
approximately 40% of males
with this syndrome have
gynecomastia (development of
mammary glands) and small
testes
(Courtesy of Children's Hospital,
Winnipeg, Manitoba, Canada.)
Fikre B. 96
97. Fetal alcohol
syndrome
in an infant
Note : the thin upper lip,
elongated and poorly
formed philtrum
(vertical groove in
medial part of upper lip)
, short palpebral
fissures, flat nasal
bridge, and short nose
(Courtesy of A.E. Chudley, MD,
Section of Genetics and
Metabolism, Department of
Pediatrics and Child Health,
Children's Hospital, Winnipeg,
Manitoba, Canada.)
Fikre B. 97
98. Prevention of Birth defects
Many birth defects can be prevented
supplementation of salt or water supplied with iodine
eliminates mental retardation and bone deformities
Placing women with diabetes under strict metabolic
control prior to conception reduces the incidence of
birth defects in their offspring
Folate supplementation lowers the incidence of neural
tube defects, such as spina bifida and anencephaly,
and also reduces the risk for hyperthermia-induced
abnormalities
Avoidance of alcohol and other drugs during all stages
of pregnancy reduces the incidence of birth defects
Fikre B. 98
99. Cont.…
A common denominator for all prevention strategies is to
initiate interventions prior to conception. Such an approach
also helps prevent low–birth-weight babies
It is important for physicians prescribing drugs to women of
childbearing age to consider the possibility of pregnancy and
the potential teratogenicity of the compounds
Recently, hundreds of children have been born with severe
craniofacial, cardiac, and neural tube defects produced by
retinoids (vitamin A embryopathy)
These compounds are used for the treatment of cystic acne
(isotretinoin, 13-cis-retinoic acid) but are also effective
topically [tretinoin (Retin-A)] for common acne and reducing
wrinkles
Oral preparations are highly teratogenic, and recent evidence
suggests that topical applications may also cause
abnormalities
Since patients with acne are usually young and may be
Fikre B. 99
