Embryology

Question 1

Fate of ectoderm

Answer 1

• CNS- central nervous system
• PNS- peripheral nervous system
• epidermis of skin, hair and nails
• Mammary, sweet and sebaceous glands
• Pituitary gland
• Enamel of teeth

Question 2

Fate of mesoderm

Answer 2

• the musculoskeletal system
• Skin- deep layers
• Abdominal and chest walls and lining
• Bowel wall (not epithelium)
• Urogential system

Question 3

Fate of endoderm

Answer 3

• epithelial lining of gastrointestinal tract, respiratory tract and bladder
• Parenchyma of thyroid gland, parathyroids, liver and pancreas

Question 4

3 germ layers

Answer 4

Ectoderm
Mesoderm
Endoderm

Question 5

Embryology: day 1

Answer 5

Fertilisation

Question 6

Embryology: day 2

Answer 6

Formation of the zygote- cell formed by fusion of egg and sperm

Question 7

Embryology: day 3

Answer 7

Cell division - formation of the morula

Question 8

Embryology: day 5

Answer 8

Late blastocyst - cavity formed within the morula

Question 9

Embryology: day 6-12

Answer 9

Implantation into uterine endometrium

Question 10

Embryology: day 8-9

Answer 10

Formation of bilaminar disc (will become the embryo)

Question 11

Embryology: week 3

Answer 11

Gastrulation- bilaminar disc becomes trilaminar disc: 3 germ layers form)

Question 12

Embryology: week 4

Answer 12

Neurulation (neural tube forms) and embryonic folding (flat disc into a cylindrical form)

Question 13

Fertilisation

Answer 13

Fusion of gametes = genetically unique individual
•Millions sperm enter the female reproductive tract
•Can survive for several days
•Travel through the uterus by muscular contractions

Relatively few sperm reach the uterine tube
•Sperm ‘conditioned’ in the tube (capacitation) before they are capable of fertilisation
•Capacitated sperm penetrate the corona radiata and bind to the zona pellucida
•After binding, the acrosome reaction occurs - sperm can penetrate the ZP
•The ZP changes so no more sperm can enter the oocyte - prevents polyspermy

Question 14

2 required process for fertilisation

Answer 14

Capacitation
Acrosomal reaction

Question 15

Capacitation

Answer 15

epithelial interactions between sperm, uterine wall
Glycoprotein coat and seminal plasma proteins covering acrosomal region removed → easier enzyme release → acrosomal reaction

Question 16

Acrosomal reaction

Answer 16

after binding to zona pellucida
Release of enzymes (eg acrosin, hyaluronidase) needed to penetrate zona pellucida

Question 17

How long are oocytes viable after ovulation

Answer 17

12-24 hours

Question 18

How long are sperm viable after ejaculation

Answer 18

Up to 6 days

Question 19

1st phase of fertilisation

Answer 19

Penetration of corona radiata: capacitated spermatozoa allowed to pass through corona radiata

Question 20

2nd phase of fertilisation

Answer 20

Penetration of zona pellucida and sperm binding
• zona pellucida- glycoprotein layer surrounding oocyte
• approx. 500 spermatozoa arrive at this layer
• sperm binding initiates release of acrosin (hydrolysis enzyme) → sperm cell penetrates zona pellucida → sperm makes contact with oocyte → cortical reaction (release of lysosomal enzymes from cortical granules of oocyte) → cortical granules initiate zona reaction, prevent further sperm penetration (polyspermy) by forming protective hyaline layer, inactive receptor sites on zona pellucida
• also activates oocyte to prepare for 2nd meiotic division

Question 21

3rd phase of fertilisation

Answer 21

Fusion of oocyte and sperm cell- forms zygote
• Interactions between integrins and ligands → adhesion of sperm, oocyte (fusion of sperm, egg plasma membranes)
• secondary oocyte completes meiosis II → forms female pronucleus, second polar body
• head, tail of spermatozoa enters oocyte → travels to female pronucleus (containing 23 chromosomes) using tail, energy generated by mitochondria
• tail, mitochondria detach → sperm nucleus becomes male pronucleus
• male, female pronuclei merge into single nucleus → cell becomes diploid
• prepared for mitotic division

Question 22

Molar pregnancy

Answer 22

• compete mole- sperm fertilises an egg that doesn’t contain any genetic material. Abnormal trophoblast (forms placenta) develops but not an embryo
• Partial mole- normal egg fertilised by 2 sperm. An embryo starts to develop but is not viable
Complications of molar pregnancy:
• retained molar tissue can lead to form a cancer (choriocarcinoma)- treatment is very successful

Question 23

Scientific relevance of molar pregnancy

Answer 23

fact that trophoblast can develop in the absence of maternal DNA suggests paternal DNA is important for trophoblast development

Question 24

Cleavage

Answer 24

series of fast mitotic divisions of zygote → increase number of cells, decrease size
• 36 hours after fertilisation → first cleavage division → 2 cells (blastomeres)
• after 3rd cleavage, blastomeres (8) form compact ball of cells connected by tight junctions (compaction)
• 3 days after fertilisation, cells ot compacted embryo divide again → mulberry-shaped 16-cell morula (composed of 2 zones: inner cell mass and outer cell mass)
• 4-5 days after fertilisation, embryo consists of approx. 100 cells
• fluid accumulates within internal cavity (blastocoel) → blastocyst

Question 25

Morula

Answer 25

composed of 2 zones: inner cell mass and outer cell mass Still surrounded by zona pellucida (glycoprotein coat)

Question 26

2 zones of blastocyst

Answer 26

Trophoblast Embryoblast

Question 27

Trophoblast

Answer 27

single layer of large flattered cells, stemming from morula’s outer cell mass; gives rise to placenta

Question 28

Embryoblast

Answer 28

20-30 pluripotent cells located on one side, stemming from inner cell mass: gives rise to embryo

Question 29

Inner cell mass

Answer 29

lies at embryonic pole of blastocyst- develops into embryo and may split into identical twins

Question 30

Outer cell mass

Answer 30

develops into the placenta

Question 31

Blastomeres

Answer 31

Cells in morula

Question 32

IVF

Answer 32

In IVF, a blastomere can be removed for genetic testing prior to transfer into the uterus

Question 33

Blastocyst hatching

Answer 33

Day 6: • blastocyst hatches from the zona pellucida before uterine implantation

Question 34

Implantation

Answer 34

1. Capture of blastocyst on endometrium- Endometrium must be ready- window of implantation 2. Blastocyst attaches more firmly to endometrium and trophoblast invade endometrium 3. complex signalling between endometrium and trophoblast Blastocyst must implant deeply enough but not too deep- endometrium closes by a fibrin plug

Question 35

Trophoblast differentiation

Answer 35

Trophoblast: • proliferates, forms 2 layers 1. Cytotrophoblast (cellular trophoblast): inner layer of moronucleated cells Produces primary chorionic villi, protrudes into syncytiotrophoblast 2. Syncytiotrophoblast: outer multinucleated mass of cells (without distinct cell boundaries) Invades decidua basalis with finger-like processes; makes enzymes that erode uterine cells; blastocyst burrows into decidua basalis surrounded by pool of blood leaked from degraded blood vessels

Question 36

Cytotrophoblast

Answer 36

at the embryonic pole proliferates

Question 37

Syncytiotrophoblast

Answer 37

invades the endometrium

Question 38

Maternal vessels and lacunae

Answer 38

Trophoblast contacts maternal vessels which form blood filled spaces called lacunae - these will bathe the forming placental villi and allow gas exchange

Question 39

Embryoblast

Answer 39

differentiates into 2 layers, forms flat bilaminar disc 1. Hypoblast - small cuboidal cells adjacent to blastocyst → yolk sac 2. Epiblast - columnar cells. Cavity forms inside (amniotic cavity). Lined with amnioblasts

Question 40

hCG

Answer 40

Human chronic gonadotropin (hCG) maintains viability of corpus luteum → secretes oestrogen and progesterone until week 8

Question 41

Amniotic cavity

Answer 41

Develops between trophoblast and epiblast

Question 42

What forms the primitive yolk sac

Answer 42

Blastocyst cavity

Question 43

Abnormal zygotes

Answer 43

Abnormal zygotes and blastocysts are common eg problems with cell division, molar pregnancy • Estimate: 50% of conceptuses are lost (spontaneous abortion) early

Question 44

Implantation problems

Answer 44

• implantation may fail - may be due to an abnormal embryo or uterine anomalies • Implantation may be ectopic – outside the body of the uterus eg uterine tube, cervix, ovary • Can result in later placental problems

Question 45

Invasive placentation

Answer 45

Trophoblast must invade – but not too far. • Placenta accreta - attachment(s) to the myometrium • Placenta increta – invasion of the myometrium • Placenta percreta – invasion of the uterine wall +/- adjacent organs • Placenta does not come away easily after birth- may result in catastrophic haemorrhage

Question 46

Pre-eclampsia

Answer 46

Pre-eclampsia: • Cytotrophoblast does not fully invade the maternal arteries • Maternal arteries do not ‘transform’ into wide, low resistance vessels. • Remain narrow and high-resistance • Restrict fetal growth • Systemic problems in the mother: -High blood pressure -Protein in the urine -Can lead to seizures (eclampsia)

Question 47

Gastrulation

Answer 47

establishes 3 germ layers • begins with formation of primitive groove (narrow depression into centre ef epiblast layer). Starts at caudal end and grows towards cranial end → cranial -caudal axis. Groove forms in dorsal side of embryo (dorsal-ventral axis). Two sides of groove- left and right side of body (bilateral symmetry) • Primitive node forms at cephalic end of primitive groove. Contains primitive pit and surrounded by slightly elevated area of ectoderm • Epiblast cells migrate towards primitive groove →move to bottom and slide under (invagination) • After invagination, cells differentiate into 3 new layers of embryonic disc (trilaminar disc) • Cells of trilaminar disc are multipotent • Some epiblast cells displace ventral hypoblast layer and form endoderm • Invaginated epiblast cells between newly formed endoderm and epiblast → mesoderm layer • Rest of epiblast forms ectoderm layer • Body axes are also established- head and ‘tail’ ends, front an back, left and right

Question 48

Primitive streak

Answer 48

Appears as a groove at the caudal (tail end) of the epiblast •Epiblast cells migrate towards the primitive streak •Invaginate through it •Settle between the epiblast and hypoblast to form a third layer, the mesoderm

Question 49

Gastrulation- clinical relevance

Answer 49

Gastrulation is a critical time - embryo is vulnerable • Insufficient mesoderm in the cranial or caudal regions can significantly affect the development of the head and lower limbs, respectively. • Laterality defects may occur - conditions of ‘abnormal sidedness’ -Situs inversus - thoracic and abdominal viscera are ‘flipped’ -Dextrocardia - the heart is ‘flipped’

Question 50

Which hormone guides tissue differentiation

Answer 50

Sonic hedgehog protein (SHH)

Question 51

Neuralation

Answer 51

• mesoderm cells around notochord differentiate into 3 specialised types of cells: paraxial mesoderm, intermediate mesoderm and lateral plate mesoderm • Notochord starts neurulation →stimulates cells of ectoderm to form neural plate • Neural plate fold and forms neural groove with edges called neural folds • Neural plate continues to grow and neural folds come together. Pinch off from surface of ectoderm to form neural tube between ectoderm and mesoderm • Neural crest cells at top of folds form many tissues eg PNS • Trophoblast continues to develop vasculogenesis • Cranial end → brain • Caudal end →spinal cord 1. Primary villi made up of cytotrophoblastic core covered by syncytial layer 2. Secondary villi form when extraembryonic somatic mesoderm cells penetrate primary villi →grow toward decidua 3. Tertiary villi form when mesodermal cells differentiate into small blood vessels → form villus capillary system → foetal contribution to placenta

Question 52

Neural tube defects

Answer 52

• The neural tube fuses along its length • Failure of closure = neural tube defects • Failure of closure caudally (tail end) = spina bifida • Can be seen on fetal ultrasound in pregnancy • Can be prevented by mother taking folic acid supplement in first 12 weeks of pregnancy • Protrusion of meninges

Question 53

Neural plate

Answer 53

Thickening of the ectoderm

Question 54

What induces neural plate formation

Answer 54

Notochord

Question 55

What do neural crest cells form

Answer 55

Many tissues including the PNS

Question 56

How does the mesoderm form

Answer 56

Epiblast cells migrate through the primitive streak and form a third layer during Gastrulation

Question 57

When are body axes established

Answer 57

Gastrulation

Question 58

Hypoblast

Answer 58

Ventral Lines yolk sac

Question 59

Epiblast

Answer 59

Dorsal Becomes germ layers Lines amniotic sac Extraembryonic mesoderm

Question 60

Blastocyst

Answer 60

Fluid accumulates within internal cavity (blastocoel) of morula

Question 61

What prevents polyspermy

Answer 61

sperm binding initiates release of acrosin (hydrolysis enzyme) → sperm cell penetrates zona pellucida → sperm makes contact with oocyte → cortical reaction (release of lysosomal enzymes from cortical granules of oocyte) → cortical granules initiate zona reaction, prevent further sperm penetration (polyspermy) by forming protective hyaline layer, inactive receptor sites on zona pellucida

Question 62

Embryo

Answer 62

developing human during the embryonic stage (to end of the 8th week)

Question 63

Fetus

Answer 63

from 9th week of development to birth

Question 64

Folding

Answer 64

week 4, the embryo starts folding •Transforms from a flat disc into a ‘cylinder’ •Folding is in two planes: •Lateral – like making a tube out of a piece of paper. The two edges curve anteriorly and fuse to close the cylinder and form the lateral and anterior abdominal walls. •Craniocaudal – the embryo’s body takes on a curved shape, from head to bum (tail).

Question 65

Lateral folding

Answer 65

like making a tube out of a piece of paper. The two edges curve anteriorly and fuse to close the cylinder and form the lateral and anterior abdominal walls. Lateral folds grow anteriorly •Fuse in the anterior midline •Fusion ‘pinches off’ most of the yolk sac •Primitive body cavity formed •Portion of the yolk sac incorporated into the body cavity - the primitive gut

Question 66

Craniocaudal folding

Answer 66

the embryo’s body takes on a curved shape, from head to bum (tail).

Question 67

Week 4 mesoderm

Answer 67

• paraxial, intermediate and lateral plate mesoderm • lateral plate mesoderm starts as a solid block but later splits

Question 68

Fate of paraxial mesoderm

Answer 68

either side of the midline • develops into the axial skeleton (vertebrae, ribs, sternum), skeletal muscles and associated dermis of the skin

Question 69

Fate of intermediate mesoderm

Answer 69

between the paraxial and lateral plate mesoderm • kidneys • Gonads (ovaries and testes)

Question 70

Fate of lateral plate mesoderm

Answer 70

split into 2 layers that associate with ectoderm and endoderm • outer/somatic/parietal layer- parietal pleural and parietal peritoneum • Inner/ splanchnic/visceral layer- visceral pleura and visceral peritoneum

Question 71

Cephalocaudal folding

Answer 71

Curving structure head to tail of embryo

Question 72

Organogenesis

Answer 72

organ systems development in the first 8 weeks

Question 73

Brain development

Answer 73

neural tube develops in week 4 and closes along its length • Rapid expansion of the cranial end of the neural tube → brain • The caudal end remains tubular → spinal cord • Failure of closure leads to neural tube defects due to exposure to amniotic fluid • Folic acid supplements in the first 12 weeks of pregnancy reduce the incidence of NTDs

Question 74

When does brain development begin

Answer 74

Week 4

Question 75

What reduces the incidence of neural tube defects

Answer 75

Folic acid supplements

Question 76

Cardiovascular development

Answer 76

heart develops as a tube in week 3 • Heart tube starts to bend in week 4- cardiac looping • Parts of tube dilate • Septae formed in weeks 4-5: grown and divide the right and left atria and the right and left ventricles • Mitral and tricupsid valves form in weeks 4-5 • Heart is not symmetrical- left and right patterning is important

Question 77

When does heart start to develop

Answer 77

Week 3

Question 78

When does cardiac looping occur

Answer 78

Week 4

Question 79

When does septae form in heart

Answer 79

Weeks 4-5

Question 80

When do mitral and tricuspid valves form

Answer 80

Weeks 4-5

Question 81

Heart anomalies

Answer 81

most common type of congenital anomaly • Septal defects • Outflow tract defects (aorta and pulmonary trunk) • Valve anomalies • Laterality defects

Question 82

Gut development

Answer 82

• primitive gut tube develops in week 4 • Segments of the gut then differentiate • Different genes involved • A concentration gradient of retinoic acid is vital for normal differentiation • Parts of the gut elongate, coil and rotate into their final positions • Positions of the small and large intestine are established in week 10 • Abdominal viscera are not symmetrical- may be affected by laterality abnormalities eg situs inversus (mirror image flip of thoracic and abdominal organs)

Question 83

When does primitive gut tube develop

Answer 83

Week 4 as lateral body folds grow and fuse anteriorly

Question 84

When are portions of the small and large intestine established

Answer 84

Week 10

Question 85

Potential MSK developmental anomalies

Answer 85

• Amelia - a limb does not develop • Meromelia - a limb is shortened • Syndactyly (webbing) - apoptosis fails or is incomplete between the digits • Polydactyly (extra digits)

Question 86

Musculoskeletal development

Answer 86

• limb buds appear in week 4- the development of the lower limb lags behind the upper limb by a few days • Week 6- hand and foot plates appear (expands at one end) and cartilage condenses in limbs • Digital rays then develop- apoptosis between rays separates the digits from each other • Limbs rotate in week 7- lower limbs rotate medially and upper limbs rotate laterally • Fingers and toes formed by week 8 • Proximo-distal, dorso-ventral and antero-posterior patterning are important

Question 87

When do limb buds develop

Answer 87

Week 4

Question 88

When do hand and foot plates appear and cartilage condense

Answer 88

Week 6

Question 89

When do limbs rotate

Answer 89

Week 7

Question 90

How do lower limbs rotate

Answer 90

Medially

Question 91

How do upper limbs rotate

Answer 91

Laterally

Question 92

When are fingers and toes formed by

Answer 92

Week 8

Question 93

How do digital rays develop

Answer 93

apoptosis between rays separates the digits from each other

Question 94

When does implantation occur

Answer 94

6-7 days post fertilisation

Question 95

Epiblasts in a 3 week embryo will become

Answer 95

Ectoderm

Question 96

The paraxial mesodermal cells form

Answer 96

Somites

Question 97

The midgut is in continuity with the

Answer 97

Yolk sac

Question 98

Circulation is formed from

Answer 98

Lateral plate mesodermal cells