Embryology Flashcards
1
Q
What is embryology?
A
The study of the origin and development of an organism.
2
Q
What is the prenatal period?
A
Before birth
38 weeks from conception to average fetal age
Three trimesters
3
Q
What are the germinal stages?
A
Two cell Four cell Eight cell Morula (16) Blastocyst (70-100)
First two weeks
Note: germinate not germ
4
Q
Blastocyst stage
Two distinct types of cells
A
Inner cell mass
Trophoblast
5
Q
Blastocyst stage
Two distinct types of cells
Inner cell mass
A
Forms embryo
6
Q
Blastocyst stage
Two distinct types of cells
Trophoblast
A
Layer of cells surrounding the cavity which form the placenta
7
Q
What happens during implantation?
A
Around day 6 post-conception
Trophoblast erodes uterine wall
Takes one week to complete
8
Q
What does it mean if inner cell mass of a single blastocyst divides?
A
Monozygotic (identical twins)
9
Q
Definition of monochorionic:
A
Twins share placenta and chorionic sac but have their own amniotic sac.
10
Q
Definition of dichorionic
A
Each twin has their own placenta, chorion and amniotic sac.
11
Q
What happens during week 2?
A
Inner cell mass divides into two fluid filled sacs:
- amniotic sac from epiblast
- yolk sac from hypoblast
Bilaminar embryonic disc: Area of contract - forms fetus.
12
Q
Likelihood of twinning
A
1 in 250 spontaneous pregnancies
13
Q
What happens during week 3?
A
- Gastrulation
- Neurulation
- Somitogenesis
14
Q
What is gastrulation?
A
Formation of trilaminar embryo
- primitive streak (groove) on dorsal surface of epiblast
- Gastrulation: invagination of epiblast cells
- Day 14-15: they replace hypoblast becoming endoderm
- Day 16: mesoderm (new third layer) formed in between the ecto and endo.
- Epiblast cells remaining on surface = ectoderm
15
Q
What is neurulation?
A
Day 22-24: directly beneath he primitive streak, mesoderm forms a notochord.
The notochord includes ectodermal differentiation (directly above it) to form a neural plate, which will bend and fold to form the neural tube.
The borders of the neural plate form the neural crest.
- Neural tube defects (NTDs) reduced by supplementing with folic acid.
16
Q
What is Somitogenesis?
A
Segmentation of the mosderm into somites.
17
Q
What happens with somitogenesis?
A
Begins at day 20:
- 1 pair form each side of notochord.
- New pair sequentially added every 90mins until 44 pairs
- Forms cranially to caudally
- Form axial body plan
18
Q
What happens during week 4?
A
Cardiogenesis
19
Q
What is cardiogenesis?
A
Heart is first functioning organ.
Mesoderm forms two tubes that fuse and start contracting.
Tube undergoes Dextral looping to form separate chambers (week 4-7)
20
Q
What happens during week 4-8?
A
Early development of other organs, tissues and limbs.
21
Q
What happens during week 9-birth?
A
Fetal period
Organs grow in size and complexity
9-12 reflexes develop
22
Q
What are signalling factors?
A
Regulate development and differentiation of organ systems.
23
Q
What is sonic hedgehog?
A
- Limb patterning
- Neural tube induction or patterning
- Somite differentiation
- Gut regionalisation
24
Q
What is Fibroblast Growth Factor?
A
- Patterning of embryonic axes
- Induction / maintenance of several cell lineages
- Coordination of morphogenetic movements.
25
What are Wnt Proteins?
Limb patterning
Midbrain development
Somite differentiation
Urogenetal differentiation
26
What is the Transforming Growth Factor-B (TGF-B)?
- Skeletogenesis
- Embryonic stem cell regulation
- Wound healing
27
What happens during week 9 to 37?
Fetal development
- Continuing growth and differentiation of organs formed during the embryonic period.
- Some organs have later development: neural, genital, respiratory, skeletal.
- Growth in size / length (2nd trimester)
- Growth in weight (3rd trimester)
28
Pregnancy complications
- Implantation failure (ectopic)
- Fetal abnormalities
- Infection: e.g. malaria, HIV, etc.
- Fetal growth restriction
- Pre-eclampsia
- Miscarriage + Stillbirth
- Pre-term delivery
*415 menstrual cycles in which unprotected sex occurs fail to produce a pregnancy of which the mother is aware*
29
Why are there pregnancy complications?
Failed fertilisation
Pre-implantation developmental arrest
Failed implantation
30
Chromosomal Abnormality Occurences
- Abnornal oocytes: >20% (>70% aged 40)
- Abnomral sperm: 7%
- Around 40% of all zygotes are chromosomally abnormal.
- Rates of abnormality are higher in women after induced ovulation in Assisted Reproduction Programmes.
- 90% of aneuploid embryos that implant, spontaneously abort in the first trimester.
Implantation failure and first trimester spontaneous abortion are biological selection mechanisms for the elimination of abnormal conceptuses.
31
What is Pre-Implantation Genetic Testing (PGT)
Blastomere biopsy: one / two blastomeres are removed from the uncompacted morula (~8 cell stage).
Blastomere loss is detected and cells are replaced.
32
Causes of Developmental Abnormalities
- Genetic e.g. Trisomy 21
- Environmental e.g. FAS
- Unknown
33
Diagnosis of Developmental Abnormalities
- Ultrasound e.g. Nuchal Translucency Test (11-14)
- Amniocentesis
- Chorionic Villus Sampling
34
What is Amniocentesis?
- Sample of amniotic fluid
- 16-18 weeks gestation
- Miscarriage rate approx. 1%
- Results within weeks
35
What is CVS?
Chorionic Villus Sampling
- Biopsy of the placenta
- 10-12 weeks gestations
- Miscarriage rate up to 2%
- Results within hours
36
Developmental Origins of Health and Disease
- Arose from epidemiological correlation studies
- Events during developmental = high rise in adulthood
- Adverse environment disrupts normal fetal growth and development
- Leads to increased susceptibility as adult to diseases e.g. cardiovascular and metabolic disorders.
37
What is the Barker Hypothesis?
- Discovered mid eighties
- Study men and women Hertfordshire
- Birth weight records since 1911
- Correlation between low birth weight and incidence of death from CVD.
- Fetal origins of Disease (FOAD) or Fetal Programming
38
Type II Diabetes and Birthweight
370 men from Hertfordshire 60-71yrs
Prevalence
40%: birth weight 5.5lbs
14%: birth weight 9.5lb
39
Recent Developments in Fetal Research
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Not limited to birth weight. Also risk factors.
Not limited to fetal period:
- pre-conception
- 1st trimester
- 2nd/3rd trimester
- Postnatal (2-4yrs)
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Adverse events at critical time points in reproductive development have individual, but significant consequences.
Placenta anomalies can affect fetal development in any trimester.
40
What are maternal influences?
Nutrition
Stress
Preterm birth
41
Why is stress a maternal influence?
Glucocorticoids
Stress can reduce birthweight
Fetal exposure to GCs results in 'DOHaD' abnormalities
42
Why is preterm birth a maternal influence?
Development outside of ideal environment (incubator vs uterus)
43
Why is nutrition a maternal influence?
Low birth weight = indicator of undernutrition
Due to maternal undernutrition or placental abnormalities.
44
What is the Periconceptual Undernourishment Sheep Model?
Sheep model of protein restriction (50%) 60 days before pregnancy - 30 days before pregnancy.
Preterm delivery + neonatal death
45
How do these maternal influences effect the fetus?
Labour is triggered prematurely
- Cortisol is released by fetal adrenal gland.
- Triggers uterine contractions.
Fetal adrenal gland is normally inactive until term.
46
Why is fetal adrenal gland inactive until term?
Premature activiation and maturation of fetus HPA axis was resultant of fetal stress caused by undernutrition.
47
Maternal stress on prematurity?
16% increased risk of preterm delivery with pre-pregnancy stress.
- Shashan et al 2009
48
Maternal Undernutrition during the Pre-implantation period
Study
- Female rats fed low protein diet (9%) only during preimplantation period (0-4.25 days after mating).
- Returned to control diet
49
Maternal Undernutrition during the Pre-implantation period
Results
Blastocysts had reduced cell numbers.
Offspring had:
- reduced birth weight (male only)
- Accelerated postnatal growth
- Hypertension
50
What is In Vitro Fertilisation?
| IVF
- >4.5 million children conceived using IVF.
- Fertilisation and pre-implantation development occurs in culture dish.
- Sub-optimal environment for embryo development = higher rates of pregnancy complications e.g. IVGR
51
What is the effect of embryo culture on Gene Expression
Embryo culture alters placental gene expression.
Imprinted genes especially susceptible.
52
What is gene imprinting?
- Normally genes are expressed biallelicaly
- Imprinting: inactivation of allele from mother or father.,
- Methylation
- Only one allele expressed - monoallelic
- Imprinted genes important for fetal growth.
53
Loss of Imprinting
e.g. H19
H19 limits body weight and cell proliferation:
- H19 normally monoallelic (maternal expression)
- After mouse embryo culture it is biallelic
- H19 negative regulator of IGF-II
- IGF-II promotes placental development and transporter activity.
- Therefore, 2x expression of H19, reduced IGF-11
54
Loss of Imprinting
e.g. Angelma, Prader-Will Syndromes
Associated with neurologic, developmental, and behavioural phenotypes plus other structural and functional abnormalities.
Higher incidence rate of imprinting disorders in children born via ART.
Many studies suggest due to embryos.
55
Undermalnutrition using pregnancy rat model
Low protein diet during pregnancy (9 vs 18)
- Low birth weight
- Obesity
- Impaired glucose tolerance
- Hypertension
Pronounced by high fat diet after weaning.
56
Dutch Winter Huger (1944-45)
Undernutrition during pregnancy:
- Reduced birth weight
- Reduced glucose tolerance in adults
- Evidence of insulin resistance in adults
- CVD
- Respiratory diseases
Imbalanced protein and carbohydrate intake during pregnancy results in low birth weight.
Micronutrients may also be important e.g. low folate and iron liked to birth weight.
57
Nutritional Mismatch
Difference between prenatal and postnatal environment.
Low nutrition prenatal (low birth weight)
Abundant food postnatal (rapid catch-up growth)
Worst possible combination for DOHaD diseases.
58
Stress during Pregnancy Rat Model
Treated to induce stress lead to
Reduced birth weight
| Reduced placental weight
59
Stress during Pregnancy Rat Model
Offspring
- Metabolic syndrome
- Obesity
- Hypertension
60
Stress during Pregnancy Rat Model
Stress and Fetal Growth
e.g. natural disasters, war, terrorism.
- elevated cortisol levels
- reduced fetal growth
- preterm delivery
Evidence that stress can be passed through genetics due to epigenetic factors:
- oocyte developed in mother as fetus - grandmother's health important.
61
Further research for stress
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Pre-conception
Preterm birth
Early life growth - lactation / diet
Transmission to future generations
Epigenetics
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