Prenatal Development

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Prenatal Development

• SSB February 2008
• L. DiLalla

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Prenatal development periods

• Zygote
• Embryo
• Fetus

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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

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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

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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

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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

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• 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)

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• 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

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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

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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

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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

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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

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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

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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 dont know why this happens

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• From Encyclopedia Britannica, 2006

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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

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Neural tube forms Approximately days 20 - 27
Courtesy of Dr. Bill Wasserman, Loyola University
Chicago
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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

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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

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Down Syndrome

• May also be related to mothers inability to
  effectively metabolize folates
• Trisomy of chromosome 21
• Main cause of mental retardation
• 1/1000 births
• Related to maternal age

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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

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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

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CNS Development

• 1st trimester
• 6th week synapses forming in spinal cord permit
  movement
• By 10th week see sucking, hiccupping,
  stretching, grasping

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CNS Development

• 2nd trimester
• New critical reflexes appear
• Contractions of the diaphragm and chest muscles
• Coordinated sucking and swallowing
• Moms dont feel these until about 18 weeks
• These are controlled by brainstem
• Mature by end of 2nd trimester

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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

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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!

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Teratogens

• Environmental Insults During Pregnancy

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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 dont know
  theyre pregnant
• Not as true now as it used to be

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Alcohol

• A PREGNANT WOMEN NEVER DRINKS ALONE. HER UNBORN
  BABY DRINKS WITH HER.

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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

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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

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Stress

• Stress during pregnancy ? increase in ADHD,
  anxiety, language delay
• Independent of postnatal depression, anxiety
• Relationship with partner is important stressor
• We dont know exactly what others are most
  important

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Why? How?

• Activity of the stress-responsive
  hypothalamic-pituitary-adrenal (HPA) axis ?
  cortisol
• Stress changes mothers 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

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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

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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!

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Drug and Alcohol Birth Defects

• Some major defects
• Defective Joints
• Major Heart defects
• Mental Retardation
• Hearing defects
• Some less severe effects
• An Uncontrollable Temper
• Hyperactivity
• Mentally challenged or slower
• Shorter attention span

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Drugs (Legal)

• Many are harmful, and many we just dont know
• So pregnant women should avoid them whenever
  possible sometimes they just cant
• E.g., Thalidomide
• Mild sedative, no longer available, for morning
  sickness
• Especially serious problems during first 2
  months, when morning sickness is most common

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Some Drugs and Complications
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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

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Tobacco-Related Defects in Children

• Decreased lung growth
• Increased rates of respiratory tract infections
• Increased otitis media
• Increased childhood asthma
• Increased risks of
• Sudden infant death syndrome
• Behavioral problems
• Neurocognitive decrements
• Rates of adolescent smoking

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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

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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

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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 mothers
• Embryonic period organs are forming and
  especially vulnerable
• Fetal period growth retardation and tissue
  damage

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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