Prenatal Development
SSB February 2008
L. DiLalla
Prenatal development periods
• Zygote
• Embryo
• Fetus
The Germinal Period
(conception to week 2)
• Cell begins to split via mitosis
• By end of week there are more than 100 cells
clustered in hollow, ball-like structure with 2
layers:
• Inner = BLASTOCYST
• Later develops into the embryo
• Outer = TROPHOBLAST
• Later provides nutrition and support for the embryo
• Zygote is deeply implanted into wall of uterus
The Embryonic Period
(weeks 2 through 8)
• Once the blastocyst is implanted, it is
called an EMBRYO
• Cells now differentiate so that different
cells take over different functions
• ORGANOGENESIS - the genesis or
formation of the different organs
The Embryo's Life Support
System
• PLACENTA - mass of tissue,
supplies oxygen and
nutrients to the embryo and
carries away waste products
• Effectively filters out most
substances, such as bacteria,
which could be harmful to the
embryo
• However, certain substances,
such as some viruses, alcohol,
and many other drugs, can
pass through it
The Embryo's Life Support
System
• UMBILICAL CORD - leads from embryo
to placenta
• AMNIOTIC SAC - surrounds embryo and
provides protective environment
• Amniotic fluid protects embryo from being
bumped around
• Amniotic fluid also maintains fairly even
temperature in womb
• Three layers form by cells migrating toward
indentation and then inward
• ENDODERM - cells will become the digestive and
respiratory systems
• MESODERM - cells will become the circulatory
system, bones, muscles, excretory system, and
reproductive system
• ECTODERM - cells will become the nervous
system and sensory receptors (ears, nose, and
eyes, for example) and skin parts (hair and nails,
for example)
• The central nervous system alone
produces 60,000 neuronal connections
per hour
• By birth, 8 billion neuronal connections
exist in the baby's brain
• Most of the brain cells are produced by
birth
Now EMBRYONIC INDUCTIONS
take place
• These are tissue interactions - means
that cells in one set of tissues affect
cells in adjacent tissues
• This is how the environment of the cells
interacts with the genetic make-up
Embryonic Inductions
• e.g., cells of the mesoderm (muscles,
skeleton, and blood) induce surrounding
ectoderm cells (central nervous system,
sensory organs, and skin) to differentiate into
the brain and spinal cord
• Genes are prepared to cause tissue to
become brain and spinal cord, but they need
to be in the correct environment - i.e., next to
the mesoderm cells - in order for this to
happen
• ALSO, they must be at the right place AT THE
RIGHT TIME - CRITICAL PERIOD
The Fetal Period
(Week 8 to Birth)
• Major body parts are already formed by now
• This is when they grow and become refined in
structure
• Fetus now responds to environmental input by
moving itself, first whole trunk, then specific
body parts in response to touch
• Can now hear baby's heartbeat through a
stethoscope at around month 4 - mom can listen too
• At 7 months, fetus sucks its thumb and can open its
eyes
• By 8 months, fetus can hear some sounds
• There is evidence that babies are born already familiar with
mom's voice and with music heard during pregnancy
Sex development
• Critical period for sex development
• Gonads are histologically distinguishable by 6-8
weeks of gestation
• At this time, if there is a Y chromosome,
testosterone causes Wolffian ducts to degenerate
and disappear
• Anti-Müllerian hormone prevents Müllerian ducts
from developing into a uterus, fallopian tubes, and
upper vagina
• Otherwise, female
• At about 3 months genitals can be identified as
male or female
Twins
• Monozygotic (MZ) versus dizygotic (DZ)
• MZ – one fertilized egg
• Not related to heredity, maternal age, fertility
drugs
• DZ – two (or more) separately fertilized
eggs
• Related to heredity, maternal age, fertility drugs
MZ twin splitting
• If egg splits in first 4 days  get 2 amnions
(diamniotic ) and 2 placenta (dichorionic )
• If egg splits during days 4-8  get 2 amnions
(diamniotic ) and 1 placenta (monochorionic )
• If egg splits during days 8-12  get 1
amnion (monoamniotic ) and 1 placenta
(monochorionic )
• Conjoined twins
• Late splitting – after day 12 (fission hypothesis)
 results in physically conjoined twins
• We just don’t know why this happens
•
From Encyclopedia Britannica, 2006
Prenatal Brain Development
• Begins with the formation and closure of the
neural tube
• Neural tube forms from the neural plate
• which begins forming 16 days after conception
• Lengthens and starts folding up, forming a groove at
around 18 days, which then begins fusing shut into a
tube around 22 days post-conception
• By 27 days, the tube is fully closed and has begun
to transform into the brain and spinal cord
Neural tube forms –
Approximately days
20 - 27
Courtesy of Dr. Bill Wasserman, Loyola University Chicago
Neural Tube Defects (NTDs)
• Major sensitive period: when neural tube is
closing (4th week after conception)
• If tube fails to seal at head end:
• Anencephaly ("lack of a cerebral cortex“)
• Always fatal
• If tube fails to seal at lower end:
• Spina bifida – part of spinal cord develops outside of
the spine
• Severity varies from symptomless to highly disabling
• Can have paralysis, sensory loss, and loss of bladder or
bowel function
Prevention of NTDs
• FOLIC ACID
• Can prevent ~60% of spina bifida cases
• Women should take at least 400
microgram/day starting 1 month before
conception, through 1st trimester
Down Syndrome
• May also be related to
mother’s inability to
effectively metabolize
folates
• Trisomy of chromosome
21
• Main cause of mental
retardation
• 1/1000 births
• Related to maternal age
Features
• There are over 300
features, but the main
ones are:
•
•
•
•
Increased neck tissue
Muscle weakness
Speckled iris of eye
Open mouth and
protruding tongue
• Short head
• Upward outward
slanting palpebral
fissures (eye slits)
• Mental retardation and
short stature become
more noticeable as child
grows
Mental retardation and Down
syndrome
• Mental retardation is the primary problem
• Average IQ is 55 (low mild mentally retarded)
• Language skills at adolescence are about age 3 level
• If reach about age 45, begin to see dementia
• Small percent of dementia has been linked to chromosome
21
• This is how the Down trisomy was originally found
• Down syndrome is NOT inherited
• Very rare for a Down syndrome person to have a
child
• Due to nondisjunction
CNS Development
• 1st trimester:
• 6th week: synapses forming in spinal cord
permit movement
• By 10th week: see sucking, hiccupping,
stretching, grasping
CNS Development
• 2nd trimester:
• New critical reflexes appear
• Contractions of the diaphragm and chest
muscles
• Coordinated sucking and swallowing
• Moms don’t feel these until about 18
weeks
• These are controlled by brainstem
• Mature by end of 2nd trimester
CNS Development
• 3rd trimester:
• Cerebral cortex begins to function toward
end of pregnancy
• Premies show very basic electrical activity in
primary sensory regions of the cerebral
cortex (perceive touch, vision, and hearing)
and primary motor regions
• Simple learning occurs
• Habituation to sound (decreased startle)
• Recognition of odors and sounds from this period
after birth
What should mothers do for good
brain development?
• Good nutrition is critical
• Stay away from drugs and tobacco
• Beware of some chemicals
• Certain occupations pose threats: e.g.,
farms, factories, laboratories, hospitals
• Beware of infections
• Rubella, chicken pox, toxoplasmosis, some
STDs
• Practice strict hygiene!
Teratogens
Environmental Insults During
Pregnancy
Teratogens
• Most influential during critical periods
• Account for about 10% of all
malformations (25% genetic, 65%
unknown)
• Difficult during early pregnancy, a very
important period, because many women
don’t know they’re pregnant
• Not as true now as it used to be
Alcohol
A PREGNANT WOMEN NEVER
DRINKS ALONE.
HER UNBORN BABY DRINKS
WITH HER.
Fetal Alcohol Syndrome (FAS)
• About 1/3 of heavy
drinkers have children with
FAS
• Occurs in 1-3 infants per
1,000
• Mental retardation is
typical for these children
• One of the most common,
preventable causes of
mental retardation in the
world
•
•
•
•
•
Some of the most common and
more visibly recognizable effects
of Fetal Alcohol Syndrome are:
Enlarged forehead
A smaller space between the nose and top-lip
Droopy-like eyes
A smaller head
Mild to severe mental retardation resulting in
learning difficulties
• Low birth weight and height that persists
• Abnormalities of the heart and other organs
Stress
• Stress during pregnancy  increase in
ADHD, anxiety, language delay
• Independent of postnatal depression,
anxiety
• Relationship with partner is important
stressor
• We don’t know exactly what others are
most important
Why? How?
• Activity of the stress-responsive
hypothalamic-pituitary-adrenal (HPA) axis 
cortisol
• Stress changes mother’s hormone levels
• Mother and infant cortisol levels are highly
correlated
• Stress later in pregnancy  children have
increased levels of cortisol, even at age 10
• This may lead to elevated depression, anxiety
Drug or Alcohol Use During
Pregnancy
• Nine times out of ten when an infant is born
addicted to any substance it is because the
mother is not aware that she is pregnant until
after most of the damage has been done
• If even a small amount of drugs or alcohol is
consumed during the first trimester of
pregnancy, the risk of having a miscarriage
before the third month is raised
Ergo…
• We DO NOT KNOW what a safe amount
of alcohol is for a pregnant woman to
consume
• SO the safest advice is to drink NO
alcohol during pregnancy!
Drug and Alcohol Birth Defects
• Some major defects:
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Defective Joints
Major Heart defects
Mental Retardation
Hearing defects
• Some less severe effects:
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•
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An Uncontrollable Temper
Hyperactivity
Mentally challenged or slower
Shorter attention span
Drugs (Legal)
• Many are harmful, and many we just don’t
know
• So pregnant women should avoid them whenever
possible [sometimes they just can’t]
• E.g., Thalidomide
• Mild sedative, no longer available, for morning
sickness
• Especially serious problems during first 2 months,
when morning sickness is most common
Some Drugs and Complications
Antibiotics
yellowed teeth, soft tooth enamel,
Anticonvulsant
drugs
cleft palate, abnormal facial
development, deformed organs,
mental retardation
Benzodiazepines
difficulties in suckling, overall
(e.g., for anxiety)
limpness
NSAIDs
can bring on premature labor
(e.g., aspirin,
damage to the inner ear
ibuprofen)
Anti-cancer drugs
stunted growth, cleft palate, spinal
defects, mental retardation
Tobacco
• Increased likelihood of tubal pregnancy
– ovum implants in Fallopian tubes
• Increased prematurity, lower
birthweight
• Smoking causes less oxygen to get to
fetus
• Passive smoke after birth causes
continued problems
Tobacco-Related Defects in
Children
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•
•
•
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Decreased lung growth
Increased rates of respiratory tract infections
Increased otitis media
Increased childhood asthma
Increased risks of:
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Sudden infant death syndrome
Behavioral problems
Neurocognitive decrements
Rates of adolescent smoking
Drugs (Illegal)
• Many drugs pass through placenta to embryo
or fetus
• HEROIN
• Children may be born already addicted to the
drug and must go through withdrawal after birth
• After birth, often hypersensitive, difficult for mom
and child to form a good relationship - maybe
because of difficult baby, maybe mom is still on
drugs or irritable or stressed out
Drugs (Illegal)
• COCAINE
• Higher risk of miscarriage, stillbirth, and
prematurity
• Babies tend to be small and have small heads
• Somewhat higher reports of SIDS
• Birth defects:
• Most have none, but may see structural abnormalities
• Often more irritable, reactive, jittery for up to 10 weeks
• Significant CNS damage may not be known until child is
older – learning problems, cognitive deficits
Effects of Teratogens
• Effect depends on organism
• Thalidomide (morning sickness): human
fetus extremely sensitive; no effect on rats
and rabbits
• Effect depends on timing
• Zygote period: fluids do not mix with
mother’s
• Embryonic period: organs are forming and
especially vulnerable
• Fetal period: growth retardation and tissue
damage
For example…
• Rubella in mothers
affects children
differently depending
on when it occurs
prenatally
• Can lead to
nonaffective
psychosis
• Can lead to deafness,
heart problems,
cataracts of the eyes,
mental retardation
0.5
0.45
0.4
0.35
0.3
0.25
0.2
0.15
0.1
0.05
0
zygote
early
late embryo early fetal
embryo
(2nd
(1st month) month)