Day 13, Lecture 1 (Sept 8): Human Development 1: The first week of development

Question 1

Gestational Age

Answer 1

• Staging of the human embryo
• Determine age based on time from last normal menstrual period
• Normal time to parturition- 40 weeks
• Staging used clinically

Question 2

Fertilization age

Answer 2

• Staging of the Human Embryo
• Determine age based on time from fertilization
• Normal time ot parturition
  
  • 38 weeks
• Staging used in embryology and in this class

Question 3

Staging of the Human Embryo

Answer 3

• Gestational age
  
  • Determine age based on time from last normal menstrual period
  • Normal time to parturition
    
    • 40 weeks
  • Staging used clinically
• Fertilization age
  
  • Determine age based on time from fertilization
  • Normal time to parturition
    
    • 38 weeks
  • Staging used in embryology in this class

Question 4

Question 5

The Embryonic period

Answer 5

• Weeks 1-8
  
  • Organogenic period
  • Time most vulnerable to teratogens

Question 6

Fetal Period

Answer 6

• Weeks 9-32
  
  • Development of organs and organ systems
  • Extensive growth
  • (luns developed sufficienctly at approximately 24 weeks to allow survivla of fetus with extensive critical care)

Question 7

What makes the earliest an infant can survival premature birth

Answer 7

• Development of the lungs
  
  • lungs developed sufficiently at approximately 24 weeks to allow survival of fetus with extensive critical care

Question 8

Postnatal develpment

Answer 8

• Development continues after birth
  
  • Respiratory system
    
    • Alveoli form in lungs
  • Cardiovascular system
    
    • Closure of fetal shunts and vessels
  • Nervous system
    
    • Continued neuronal development

Question 9

What are the key processes that must occur for a fertilized egg to give rise to the adult

Answer 9

1. Proliferation
2. Growth
3. Differentiation
4. Pattern Formation
5. Morphogenesis

Question 10

What is differentiation

Answer 10

• Process by which cells or tissues become different from one another
• Progressive acquisition of structural and biochemical specializations leading to unique or highly developed cellular functions

Question 11

There are how many different specialized cells in adult human

Answer 11

200

Question 12

Totipotent

Answer 12

• Can differentiate into all cell types
  
  • examples
    
    • Zygote
    • Morula

Question 13

Pluripotent

Answer 13

• Differentiate into many cell types
  
  • examples
    
    • Inner cell mass
    • Epiblast

Question 14

Multipotent

Answer 14

Differentiate into restricted group of cells

Question 15

Unipotent

Answer 15

Determined as to differentiated cell to form

Question 16

Since all cells contain the same set of genes (genomic equivalence) how can genes direct development when same in all cells?

Answer 16

• Differential Gene Activity
  
  • Different genes are turned on and off during development leading to specific genes being expressed in the differential cell

Question 17

Does differential gene acitvity lead to irreversibly turning off of genes?

Answer 17

• No
• Think about Dolly and iPS cells

Question 18

Induced Pluripotent Stem Cells (iPS cells)

Answer 18

• Reverse differentiated cell to pluripotent state
• Express factors found in pluripotent cells
• Another demonstration of genomic equivalence
• Provide possible pluripotent stem cells to be used clinically
• Genotype same as patient if use adult cell from patient

Question 19

Regulation of Differential Gene Activity occurs at Mutliple Levels

Answer 19

• Differential gene transcription
  
  • Transcrption factors
  • Histone Methylation
  • DNA Methylation
• Selective Nuclear RNA processing
• Selective messenger RNA Proccessing
• Differential Protein Modification

Question 20

Cells must acquire _______ to determine what to form and when to undergo differentiation

Answer 20

• Positional Information

Question 21

Example of differntation with loss of pattern formation

Answer 21

Teratoma

Question 22

Positional Information

Answer 22

• Receive cues from environment
  
  • Cell-Cell interactions
  • Soluble factors including growth factors and cytokines
  • Extracellular matrix
• Lineage
  
  • Restricts response to positional information

Question 23

Specification of Little Verse Great Digit

Answer 23

Question 24

Answer 24

Question 25

Apoptosis is an example of

Answer 25

• Morphogenesis

Question 26

Syndactyly is a malformation due to

Answer 26

• Altered Morphogenesis
• Lack of apoptosis in interdigital regions

Question 27

Question 28

Egg at Fertilization

Question 29

Cleavage

Answer 29

• Specialized cell division whereby daughter cells divide rapidly reducing size with each division
• Partition of cytoplasm of zygote into small cells (blastomeres) without an increase in cytoplasmic mass
• Reason for cleavage
  
  • Zygote very large (1000 micrometers) compared to normal cell (10 micrometers)

Question 30

Morula

Answer 30

• 12-16 cell stage
• formed on 3rd day

Question 31

Compaction of Morula

Answer 31

• compaction occurs 4 days post fertilization
  
  • first morphogenesis in the embryo
• Formation of tight junctions between outer blastomeres
  
  • Tight junctions allow for the partitioning of inside and outside
  • Dependent on the presence of E-cadherin in outer layers of blastomeres
  • Forms two distinct lineages
    
    • outer and inner cells
  • Blastomeres no longer totipotential

Question 32

Blastocyste formation

Answer 32

• 4 day post fertilization
• Following compaction
• Forms fluid filled cavity- blastocyst cavity
• First sorting of embryonic cells into lineages
  
  • Inner cell mass cells will form embryo
    
    • Pluripotenital
  • Trophoblast
    
    • will form protective membranes
    • Extraembryonic membrane (chorion)

Question 33

Hatching of Blastocyst

Answer 33

• Weakening of Zona Pellucida
• Blastocyste squeezes out of zona pellucida
  
  • Formation of floating blastocyst (6th day of development)

Question 34

Question 35

Implantation

Answer 35

• end of the first week of development
• Floating blastocyste makes contact with the endometrial lining of the uterus
• Trophoblast will form two distinct layers of cells
  
  • Cytotrophoblast
    
    • Actively dividing
    • gives rise to Syncytiotrophoblast
  • Syncytiotrophoblast
    
    • nuclei don’t divide
    • highly envasive into endometrium allowing for implantation
      
      • Produces matrix metalloproteinases (MMPs) to promote invasion
        
        • (note: the most invasive carcinoma known is choriocarcinoma similar process of invasion used during metastasis)
      • Produces protein and steroid hormones
        
        • ex. hCG, which stops the menstrual cycle

Question 36

Reorganization of the inner cell mass

Answer 36

• occurs at the end the first week of development
• Delaminates into:
  
  • Hypoblast layer- forms extraembryonic structures
  • Epiblast- Forms embryo proper

Question 37

• Review of 1^st week of Development

Question 38

Spontaneous Abortion

Answer 38

• Spontaneous abortion thought to be as high as 60%
  
  • almost all are early in pregnancy
    
    • only about 5% are after 8 weeks of development
• Many times women don’t realize they are pregnant
• Found out due to careful monitoring of early pregancy that is now possible
• about 50% is due to chromosomal abnormalities

Question 39

Abnormal Implantation sites

Answer 39

• any place place other than the normal (superior part of the body of the uterus)
  
  • most frequent normal location is in the posterior part of the superior body of the uterus
• Placentia Previa
  
  • implantation in the lower part of the uterus
  • placenta is covering the internal os of uterus
  • may result in early placential
  • fetus must be delivered by cesarean section
• Tubal Implantation
  
  • is the most common ectopic site (about 98%)
    
    • Result of delayed transport along uterine tube
    • In approximately 50% of tubal pregnancies if the embryo remains will result in rupture 6-8 weeks post-ferilization. leading to potential death of mother due to internal bleeding
• Ovarian and abdominal implantation
  
  • Relatively rare
  • Risk of internal bleeding high

Question 40

Lithopedion

Answer 40

• Abdominal pregnancy
• results in fetus becoming calcified if it remains in abdomen

Question 41

Multiple pregnancy

Answer 41

• Natural cycle:
  
  • Twins
    
    • 1:90
  • Triplets
    
    • 1:90²
  • Quadruplets
    
    • 1:90³
• ​2/3 of twins dizygotic
• 1/3 monozygotic

Question 42

Monozygotic Twinning

Answer 42

• Formation of Identical Twins from splitting of Blastomeres
  
  • Twinning occurs during cleavage
  • two morulas are formed forming two embryos demonstrates
    
    • blastomeres are totipotential
    • Blastomeres can regulate
• Formation of Identical Twins from splitting of inner cell Mass
  
  • Twinning occurs at blastocyst stage
  • inner cell mass divides forming two embryos demonstrates
    
    • inner cell mass cells are pluripotential
    • inner cell mass cells can regulate

Question 43

In Vitro Fertilization

Answer 43

• Can be used as an effective treatment for infertility
• Indications for IVF
  
  • Blocked fallopian tubes or pelvic adhesions
  • Male factor infertility
  • Failed 2-4 cycles of ovarian stimulation with intrauterine insemination
  • Unexplained infertility
  • Vasectomy or tubal ligation
  • Preimplantation genetic diagnosis
• In Vitro Fertilization Protocol
  
  • Usually have 10-15 blastocysts per cycle
  • Implant no more than 3 blastocysts
  • Freeze remaining blastocysts for subsequent use

Question 44

Preimplantation Genetic Diagnosis

Answer 44

• Screening of embryos for genetic disorders
• Perform genetic diagnosis on embryos produced by IVF
• Implant embryos not carrying genetic disorde
• Can be screened for monogenic disorders, chromosomal structural aberrations, or X-linked diseases
• Frequently screened disorders
  
  • Cystic Fibrosis
  • Beta-thalassemia
  • Fragile X syndrome
  • Duchenne muscular dystrophy
• Procedure
  
  • Remove one blastomere from morula
    
    • possible because
      
      • blastomeres are totipotent
      • morula can regenerate
  • Perform genetic analysis
  • Only implant blastocysts not carrying genetic disorder