Embryo to Fetus

Question 1

PRENATAL PERIODS

Answer 1

PRE-IMPLANTATION
1-5 DAYS
EMBRYONIC
DAY 6 TO WEEK 8
FETAL
9 WEEKS - BIRTH

PRE-IMPLANTATION PERIOD FIRST WEEK OF LIFE
EMBRYONIC PERIOD/ WEEKS 2-8
A. FETAL MEMBRANES ARE ESTABLISHED
B. GERM LAYERS LAID DOWN IN EMBRYONIC DISC
C. RAPID GROWTH
D. BEGINNING OF ALL INTERNAL AND EXTERNAL STRUCTURES DEVELOP
E. ORGANOGENESIS: ALL ORGAN SYSTEMS HAVE BEGUN FORMING BY END OF WK 8
D. MAJOR EXTERNAL FEATURES ARE RECOGNIZABLE
E. CRITICAL PERIOD OF DEVEOPMENT
FETAL PERIOD/ 9 WEEKS TO BIRTH
A. SYSTEMS DEVELOP FURTHER
B. DEVELOPMENTAL CHANGES ARE NOT SO DRAMATIC
C. RATE OF BODY GROWTH IS REMARKABLE

During the embryonic period, all organ development begins. Also, during this time, the human is most sensitive to teratogens.

Hensen’s node helps set up left-right axis

Question 2

LEFT RIGHT AXIS FORMATION

Answer 2

Question 3

How Does the Embryo Know Its Left From Its Right?

Answer 3

THIS SLIDE SHOWS THE NODE – AN AREA IMPORTANT IN BREAKING SYMMETRY AND DEFINING THE L-R AXIS

Question 4

Nodal Cilia Beat in a Right to Left Direction

Answer 4

Circular power stroke right-left

motors: kinesin (red) and dynein (pink)

KO mouse, no cilia-no left-right axis

Question 5

Primary Cilia in The Node are Needed for Left Right Asymmetry

Answer 5

Question 6

Nodal Flow Generates Left Right Asymmetry

Answer 6

A = time lapse image showing nodal vesicular parcel (NVP) at 2 second intervals moving left to right

B= Time lapse images showing release through smash phase for NVP

C= diagram of nodal flow

Question 7

Nodal Flow Generates Left Right Asymmetry models

Answer 7

PKD1L1 Polycystic kidney disease like protein

SHH = sonic hedgehog . signaling molecule (protein) instagates reactions.

Question 8

SOME OF THE MOLECULAR PLAYERS IN NODAL FLOW

Answer 8

Nodal turns on Pitx2 (transcription factor) left side

Lefty inhibits snail

snail (transcription factors) right side

Question 9

What Happens When Nodal Flow Does Not Occur??

Answer 9

Situs inversus (organs not in normal place)

Question 10

Embryonic Folding

Answer 10

Longitudinal Folding
Transverse Folding

THE PURPOSE OF FOLDING IS TO TRANSFORM THE FLAT THREE ALYERED EMBRYONIC DISK INTO A CYLINDER (WHICH IS WHAT ARE BODIES ARE)

Question 11

Longitudinal Folding – From Langman

Answer 11

Question 12

TRANSVERSE FOLDING- from Langman

Answer 12

Question 13

FOLDING REVIEW

Answer 13

Question 14

CARNEGIE STAGES FOR HUMAN EMBRYOS

Answer 14

Question 15

MRI Imaging of Human Embryos

Answer 15

EXAMPLES OF HUMAN EMBRYOS MADE WITH MRI MICROSCOPE

CAN SEE THEM IN 3D

CAN BE ROTATED

CAN LOOK AT SECTIONS THRU EMBRYOS
NOTICE DETAIL IN IMAGES - CAN YOU ID STRUCTURES?
MUCH BETTER QUALITY THAN ULTRASOUND

Question 16

FETAL PERIOD

Answer 16

WEEKS 9-38

FIGS SHOW SECOND AND THIRD TRIMESTER

PHENOMENAL WEIGHT GAIN ESPECIALLY IN LAST FEW WEEKS OF PREGNANCY

ORGAN SYSTEMS NOT ONLY DEVELOP BUT ALSO BEGIN TO FUNCTION DURING FETAL PERIOD

Characterized by rapid growth

Week 9: head=1/3 total length of fetus.

Organ systems begin to function prenatally.

By the end of gestation, the fetus drinks about a pint of amniotic fluid every day.

Sense of taste: depending on what’s in the amniotic fluid, fetus may drink more or less

Kidneys make about 450 mL of “urine” every day. The urine excretes into the amniotic cavity and recycles again and again. Much more dilute than adult urine.

If the kidneys don’t produce enough urine, there’s oligohydramnios (not enough amniotic fluid which can lead to abnormal limb development)

Endocrine glands functine prenatally. Fetus decides when to be born.

Respiratory system is the last to finish development.

Dipalmitoyl lecithin spreads water in the lungs which leads to proper functioning. hyaline membrane disease (infanant cannot breathe) without dipalmitoyl lecithin

Question 17

Fetal Growth Curve

Answer 17

Question 18

Fetal body scale changes over time

Answer 18

Question 19

Changes in Relative Size of the Head

Answer 19

Question 20

FETAL PHYSIOLOGY

Answer 20

INTESTINE

KIDNEYS

ENDROCRINE GLANDS

RESPIRATORY SYSTEM
DIPALMITOYL LECITHIN
HYALINE MEMBRANE DISEASE

INTESTINE:

1. 500 ML AMNIOTIC FLUID SWALLOWED/DAY AT END OF PREGNANCY 2. MOST ELECTROLYTES, WATER, GLUCOSE, UREA, STEROID HORMONES ARE ABSORBED BY SMALL INTESTINE
2. REPLACES WATER LOST THROUGH URINATION
3. CONTROLS VOLUME OF AMNIOTIC FLUID
4. SENSE OF TASTE DEVELOPS PRENATALLY

KIDNEY:

1. PLACENTA = EXCRETORY ORGAN DURING PREGNANCY
2. KIDNEY PRODUCES URINE - RELEASED INTO AMNIOTIC FLUID - ABOUT 450 ML A DAY AT END
3. IF NO KIDNEY - AMOUNT OF AMNIOTIC FLUID IS LOW = OLIGOHYDRAMNIOS

ENDROCRINE GLANDS

1. FUNCTION BY 9-10 WEEKS
2. GENERAL SAME FUNCTIONS AS IN ADULT
3. MAY INITIATE LABOR

RESPIRATORY SYSTEM:

1. RHYTHMIC BREATHING BEFORE BIRTH - PRACTICE MOVEMENTS
2. SURFACTANT NEEDED FOR PROPER INFLATION OF LUNGS AT BIRTH

Question 21

METHODS TO STUDY FETUS

Answer 21

1. PLACENTAL FUNCTION - HCG CAN BE MONITORED EASILY - IF LOW COULD BE A THREATENED PREGNANCY
2. AMINO - DONE AFTER 14 WEEKS -LATE IN PREGNANCY - ENOUGH AMNIOTIC FLUID
   THEN CELLS MUST BE GROWN - SEVERAL WEEKS TO GET RESULT
3. A-FETOPROTEIN IN FLUID CAN INDICATE OPEN NEURAL TUBE DEFECT
4. SEX CAN BE DETERMINED
5. RECOMBINANT PROBES - MUSC DYSTROPHY, HEMOPHILA, HUNTINGTON’
6. CVB CAN BE DONE EARLY IN FIRST TRIMESTER
7. TAKE PLUG OF CELLS FROM CHORION
8. DO NOT NEED TO CULTURE SO CAN GET RESULT FAST
9. CAN NOT DETECT NTD W/ CVB
10. CAN DO OTHER DNA TESTS
11. MAY BE SLIGHTLY MORE RISK OF SPON ABORTION FOLLOWING CVB
12. BLASTOCYST ANALYSIS BEFORE IMPLANTATION
13. SETS PRENATAL TESTING CLOCK BACK TO 8CELL STAGE
14. FERTILIZE EGGS IN VITRO AND REMOVE A BLASTOMERE BY PIPETTE
15. EXAMINE DNA FOR MUTANT GENES
16. USED PROBES FOR CYSTIC FIBROSIS
17. PUT ONLY GOOD EMBRYOS BACK IN MOTHER’S UTERUS
18. COST = $2000 FOR BABI, BUT LESS THAN CARE OF CHILD WITH SERIOUS DISEASE
19. ULTRASOUND VALUABLE - CAN DIAGNOSE A LOT OF PROBLEMS
20. SIMPLE, RAPID, NO HARM, NO DISCOMFORT TO MOTHER

Placenta function: take blood or amniotic fluid sample, look for biomarkers

hCG goes up during pregnancy, if it’s too high, it can indicate a hydatidaform mole

Amniocentesis (about 30 mL taken from uterus)

1. take the fluid and analyze it. If alpha fetaprotein is too high, the neural tube isn’t closed
2. culture cells, check DNA. can check for trisomy 21, huntington’s disease, etc.

Cannot perform until about 14 weeks. There’s also a danger that the needle may induce spontaneous abortion

Chorionic Villus Biopsy: some cells are taken from the placenta. May be done in embryonic stage, much earlier than fetus. disadvantates: needle may induce spontaneous abortion.

Question 22

METHODS TO STUDY FETUS CONTINUED

Answer 22

IVF labs

BABI–> take out one blastomere

the tests are expensive. anywhere from 20,000 to 100,000

Question 23

2 vs 3-Dimensional Ultrasound

Answer 23

3D high res render surface of fetus

4D adds time (video)

Question 24

Birth Statistics

Answer 24

OCCURS 266 DAYS OR
38 WEEKS AFTER
FERTILIZATION
LENGHT = 360mm
WEIGHT = 3400g

LOW BIRTH WEIGHT BABIES
SMALL FOR DATES
PREMATURE

Premature birth: before 37 weeks of gestation.

PB accounts for 35% of deaths in first year of life.
Costs exceed $26 billion/year
Risk factors include multiple pregnancies – twins, triplets etc, gentialurinary infection, smoking, extreme body weight;
Also depression, stress, poor diet, periodontal disease..
Short cervical length consistent predictor of premature birth – sometimes can suture around cervix

If newborn weighs under 2,500 grams, low birth weight

Question 25

INTRAUTERINE GROWTH RETARDATION

Answer 25

PLACENTAL FACTORS:

1. REDUCED BLOOD FLOW - HYPOTENSION, RENAL DISEASE, KNOT IN CORD
2. DYSFUNCTION - NOT NORMAL PLACENTA, SMALL, BRUISED, UNDER DEVELOPED, RETARDS GROWTH
3. MULTIPLE PREGNANCY

GENETIC:
1. SMALL MOTHERS HAVE SMALL BABIES
2. SMALL BABIES RUN IN SOME FAMILIES
3. CHROMOSOMAL ABERRATIONS - DOWN’S SYNDROME, TRISOMY 18
ENVIRONMENTAL:
1. MALNUTRITION - FAMINES, POOR DIET
2. CIGARETTE SMOKING - FETAL TOBACCO SYNDROME
3. DRUGS - LSD, HEROINE, MORPHINE, AMPHETAMINES, ETOH

SMALL BABIES WHETHER PREMATURE OR SFD ARE MORE VULNERABLE AND LESS LIKELY TO SURVIVE!!

Placental factors: underdeveloped, twins/triplets, bruised, knots in cord

Genetic factors: small women–>small babies

Environmental factors: smoking–>small babies (active or passive smoking), alcohol is toxic to neural crest cells. recreational drugs, etc.

Question 26

FETAL SURGERY

Answer 26

Fetal surgeries have been done for more 20 year – but dangerous

May be used to treat spina bifida or diaphragmatic hernias (improperly formed diaphragm-guts in thoracic cavity…fatal condition normally)

But risky for both mother and fetus

Because this is very dangerous- is only done in rare case

For example – has been used to treat diaphragmatic hernia, but dangerous and may not be very effective

Also may be used to treat spina bifida but again controversial

Best use is when fetal surgery accompanies delivery.

E.g. fetus has tumor in thorax that will prevent breathing
remove tumor using fetal surgery just before delivery, then baby can breath when born
Called exit surgery.

Likely fetal surgery will become obsolete
Replaced by stem cell and gene therapy.

E.g. stem cells could be used to treat sickle cell anemia.

Question 27

Fetal Origins of Adult Health and Disease– a new science

Answer 27

New branch of medicine
Recognizes that what we are as adults and our adult health can be linked to the conditions we were exposed to in utero
Recognized only recently
Intensively researched during last 10 years
Heart disease – early onset associated with birth weight – smaller babies tend to have increased risk for heart disease

Obesity – If mothers are obese during pregnancy, their children will tend to be obese. If mothers fat is surgical removed to restore normal weight- he subsequent children are more likely to also have normal weight

Diabetes – diabetic mother – has high glucose- this disrupts fetal metabolism- predisposes her children to type II diabetes

Air- cord blood is loaded with the air pollutants a mother breathes. New borns have PAH (polycyclic aromatic hydrocarbons) in blood. Evidence they have already affected DNA even before birth

Stress- If mothers are stressed during pregnancy – they are more likely to have anxious children and children with schizophrenia

What happens in utero affects the rest of life. some adult diseases originate in utero

Barker Theory-makes conditions come on sooner than they otherwise would.

IF metabolism is set slower in utero, it stays slow the rest of life–>tendency towards obesity

Question 28

The Barker Theory

Answer 28

Reduced fetal growth is strongly associated with a number of chronic conditions later in life. These chronic conditions include coronary heart disease, stroke, diabetes, and hypertension.

Also called Thrifty phenotype.

This increased susceptibility results from adaptations made by the fetus in an environment limited in its supply of nutrients.

Like between fetal birth weight and later early onset of adult disease first made by David Barker 20 years ago

Poorest areas in England and Wales had highest rates of heart disease. Found birth weights lower in poorer regions. Strong correlation between birth weight and later heart disease.

Not taken seriously at first but now many studies have been done confirming his observations. Why- if resources are limited in utero, fetus may not be able to develop all organs fully, may also put resources in to brain at expense of the heart and other organs. Later in life, the deficiencies may take their toll.

Question 29

Developmental Origins of Adult Health and Disease

Answer 29

The DOHaD hypothesis states that exposure to an unfavorable environment during development (either in utero or in the early postnatal period) programs changes in fetal or neonatal development such that the individual is then at greater risk of developing adulthood disease.

Flip side of this hypothesis

Exposure to a good environment in utero will favor development of a healthy adult

Could be very important in public health – an improvement of quality of life

Pregnant women may make simple adjustments during pregnancies and help their fetus develop in a way that helps them remain healthy longer in adulthood.

Question 30

DOHaD hypothesis

Answer 30

Question 31

Specific Example - Possible relationship between uterine environment and development of type II diabetes

Answer 31

Question 32

How could a fetus reset its metabolism (or anything else) in a way that would affect it as an adult?

Answer 32

The answer may lie in epigenetics

= Study of gene activity that do not involve changes in the genetic code but still get passed down to successive generations.

Patterns of gene expression governed by the epigenome- which marks genes telling them if they should turn off or on

Or if they should be highly or lowly expressed.

Question 33

Epigenetics

Answer 33

Involves mitotically and meiotically inheritable changes in gene expression that do not involve a change in the DNA sequence itself.

Often accomplished by methylating select regions of DNA (as we saw in genomic imprinting)

Question 34

Regulatory Proteins Have Two Functions

Answer 34

1. SWITCH SPECIFIC GENES ON OR OFF

A gene regulatory protein attaches to a specific sequence of DNA on one or more genes. Once there, it acts like a switch, activating genes or shutting them down.

2. RECRUIT ENZYMES THAT ADD AND REMOVE EPIGENETIC TAGS

Gene regulatory proteins also recruit enzymes that add or remove epigenetic tags. Enzymes add epigenetic tags to the DNA, the histones, or both. Epigenetic tags give the cell a way to “remember” long-term what its genes should be doing.

Question 35

Epigenetic silencing of a gene often involves methylating the DNA in that gene

Answer 35

methylation can turn off a gene

regulatory protein-temporary; methylation-permanent

what you eat can affect the methylation of DNA. gene expression is then affected.

Question 36

Experiences Are Passed on to Daughter Cells

Answer 36

As cells grow and divide, cellular machinery faithfully copies epigenetic tags along with the DNA.

This is especially important during embryonic development, as past experiences inform future choices.

A cell must first “know” that it is an eye cell before it can decide whether to become part of the lens or the cornea.

The epigenome allows cells to remember their past experiences long after the signals fade away.

Question 37

DNA METHYLATION – USUALLY OF CYSTEINE

Answer 37

folic acid, betaine, choline, B vitamins can all methylate DNA

Question 38

DNA METHYLATION CAN BE STUDIED USING AGOUTI MICE

Answer 38

Agouti=brown

Question 39

Experiment showing how BPA in diet can effect coat color (DNA methylation and gene expression)

Answer 39

Question 40

Can effects of BPA be reversed by diet?

Answer 40

Question 41

Don’t Count Dad Out

Answer 41

So if a pregnant mother’s diet can affect the child’s epigenetic outcome, can dad’s diet do the same? Quite possibly, according to scientists who delved into the well-kept, historical records of annual harvests from a small Swedish community. These records showed that food availability between the ages of nine and twelve for the paternal grandfather affected the lifespan of his grandchildren. But not in the way you might think.

Food abundance for the grandfather was associated with a reduced lifespan for his grandchildren.

Shortage of food for the grandfather was associated with extended lifespan of his grandchildren.

Food abundance, on the other hand, was associated with a greatly shortened lifespan of the grandchildren.

Early death was the result of either diabetes or heart disease.

Could it be that during this critical period of development for the grandfather, epigenetic mechanisms are “capturing” nutritional information about the environment to pass on to the next generation?

Question 42

Genomic Imprinting revisited

Answer 42