Early Foetal Development

Question 1

what are the different methods of measuring time in embryo-foetal development?

Answer 1

fertilisation age

gestational age

Carnegie stage

Question 2

what is the fertilisation age?

Answer 2

(also known as conceptual age)

1. Measured from time of fertilisation (assumed to be +1 day from last ovulation)
2. Difficult to know time of fertilisation exactly (unless IVF)

Question 3

what is the gestational age?

Answer 3

1. Calculated from the time of the beginning of last menstrual period (LMP)
2. Determined by fertilisation date (+14days) if known, or early obstetric ultrasound and comparison to embryo size charts

Question 4

what is the Carnegie stage?

Answer 4

1. 23 stages of embryo development based on embryo features not time
2. Allows comparison of developmental rates between species

Covers the window of 0-60 days fertilisation age in humans

Question 5

what are the phases of ovarian cycle?

Answer 5

Question 6

stages based on embroylogical development?

Answer 6

1. germinal stage
2. embryonic stage
3. foetal stage

Question 7

what happens during the germinal stage?

Answer 7

(14-16 days post-fertilization):

1. establishing the early embryo from the fertilized oocyte
2. Determining two populations of cells:
   
   1. pluripotent embryonic cells (contribute to fetus)
   2. Extraembryonic cells (contribute to the support structures eg placenta)

Question 8

what happens during the embryonic stage?

Answer 8

(16-~50 days post fertilization):

1. Establishment of the germ layers and differentiation of tissue types
2. Establishment of the body plan

Question 9

what happens in the foetal stage?

Answer 9

(~50 to 270 days post-fertilization or ~8 to ~38 weeks):

1. Major organ systems now present
2. Migration of some organ systems to final location
3. Extensive growth and acquisition of fetal viability (survival outside the womb)

Question 10

what are the stages in the first few days from fertilisation to blastocyst?

Answer 10

• Zygote undergoes a series of mitotic divisions (cleavage divisions) to form a 2 cell embryo, 4 cell embryo and 8 cell embryo
• 8 cell embryo proceeds with further mitotic divisions à morula à blastocyst
• The zona pellucida (protein shell) that surrounds the embryo is present for all stages

Question 11

when does the maternal to zygote transition occur?

Answer 11

• Until 4-8 cell stage, the genes of the embryo are not transcribed
• Embryo is dependent on maternal mRNAs and proteins to get through the first divisions
• These mRNA and proteins are synthesized and stored during oocyte development (i.e. pre-ovulation)
• Failure to synthesise, store or interpret these mRNAs and proteins during oogenesis can impair embryonic development.

Question 12

what occurs during embryo compaction?

Answer 12

• Starts formation of first 2 cell types
• Around the 8-cell stage or later:
• Outer cells become pressed against zona
• Change from spherical to wedge-shaped.
• Outer cells connect to each other through tight gap junctions and desmosomes
• Forms barrier to diffusion between inner and outer embryo
• Outer cells become polarised

Question 13

what is the composition of the blastocyst?

Answer 13

Question 14

what is required for the blastocyst to implant?

Answer 14

must escape the zona pellucida via hatching (day 5-6)

this is done via:

enzymatic digestion

cellular contraction

Question 15

what occurs during peri-implantation events?

Answer 15

(day 7-9)

trophectoderm lineage separates further

inner cell mass separates

Question 16

what does the trophectoderm lineage separate into?

Answer 16

• trophoblast cells fuse to form syncitiotrophoblast
• Syncitiotrophoblast invasion destroys local maternal cells in the endometrium
  
  • Creates interface between embryo and maternal blood supply (breaks down capillaries)
• cytotrophoblast cells remain individual and divide to provide source of syncitiotrophoblast cells

Question 17

what do inner cell mass seperate into?

Answer 17

• epiblast: from which the fetal tissues will be derived.
• hypoblast: which will form the yolk sac (extraembryonic structure)
  
  • important in gut development and early haematopoiesis

Question 18

what is the final stage before gastrulation?

Answer 18

bilaminar embryonic disc formation

Question 19

what happens during bi-laminar embryonic disc formation?

Answer 19

day 12+

• Some epiblast cells become separated from the epiblast by the formation of a new cavity – the amniotic cavity.
• The epiblast cells on the top create a structure called the Amnion
• These amnion cells will contribute to the extra-embryonic membranes.
• This leaves a two-layer disc of epiblast and hypoblast, sandwiched between cavities. (bilaminar embryonic disc)
  
  • This epiblast will give rise to the fetal structures and organs
• Embryo is now ready for gastrulation

Question 20

how does a pregnancy test work?

Answer 20

detects beta hCG subunit (Human chorionic gonadotropin)

in blood or urine

hCG is secreted by syncytiotrophoblasts

Question 21

what are the cell lineages from the initial morula?

Answer 21

Question 22

what is gastrulation?

Answer 22

Bilaminar disk differentiates to establish 3 primary germ layers= gastrulation

Question 23

what occurs during gastrulation?

Answer 23

• 13+ days after fertilisation:
• Thickened structure form along midline in the epiblast= primitive streak
  
  • Near caudal end of bilaminar embryonic disc
• The primitive streak divides the major body axis of the embryo including
• the primitive streak it expands to form the primitive node which contains a circular depression= primitive pit
• The depression continues along the midline of the epiblast towards the caudal end of the streak= primitive groove
• Cells of the epiblast migrate inwards towards the streak
  
  • Detach from the epiblast and slip beneath into the interior of the embryo = invagination
• The first cells to invade through the primitive groove invade the hypoblast and displace its cells
• The hypoblast cells are replaced by the new proximal cell layer known as definitive endoderm
• The remaining cells of the epiblast are known as the ectoderm
  
  • Forms the most exterior distal layer
• Some of the invaginated epiblast cells remain in the space between ectoderm and definitive endoderm
  
  • These cells form a germ layer= mesoderm
• When the formation of definitive endoderm and mesoderm is complete, the epiblast cells no longer migrate towards primitive streak
• Through gastrulation the ectoderm continues to form from the cranial to caudal end of embryo establishing 3 distinct primary germ layers

Question 24

what organs form in the different germ layers?

Answer 24

Question 25

what is the notochord?

Answer 25

organising centre for neurulation and mesoderm development

Question 26

when does the notochord form?

Answer 26

* day 14 * Notochord is a rod-like tube structure formed of cartilage-like cells * Forms along the embryo midline, under the ectoderm

Question 27

what is neurulation?

Answer 27

forming the neural tube and CNS

Question 28

what are the steps in neurulation?

Answer 28

neural groove formation neural tube formation closure of neural tube

Question 29

how does the neural groove form?

Answer 29

* Notochord signals direct the neural plate ectoderm to invaginate forming neural groove * Creates two ridges (neural folds) running along the cranio-caudal axis * Neural crest cells specified in neural folds

Question 30

what happens once the neural groove is formed?

Answer 30

* Neural folds move together over neural groove * Ultimately neural folds fuse, forming a hollow tube (neural tube) * Neural tube overlaid with epidermis (ectoderm) * Migration of the neural crest cells from folds * **Neural tube initially open at each end** * Closure at head end: ~ day23 * Closure at tail end: ~ day27 * Closure at head end precedes formation of brain structures

Question 31

what happens on failure of neural tube closure?

Answer 31

common developmental defect * **Anencephaly** (absence of most of the skull and brain) arises from failure to close at the head end * **Spina bifida-** open neural tube at birth, usually lower spine due to failure to close tail end– varying severity

Question 32

what are the derivatives of neural crest cells?

Answer 32

exoderm derived, plastic and migrate extensively during development 1. cranial NC 2. cardiac NC 3. trunk NC 4. vagal and sacral NC

Question 33

what do cranial NC differentiate into?

Answer 33

cranial neurones, glia, lower jaw, middle ear bones (ossicles), facial cartilage

Question 34

what do cardiac NC diffrentiate into?

Answer 34

* aortic arch/pulmonary artery septum, large arteries wall musculoconnective tissue

Question 35

what do trunk NC differentiate into?

Answer 35

dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters, melanocytes

Question 36

what do vagal and sacral MC differentiate into?

Answer 36

* parasympathetic ganglia and enteric nervous system ganglia

Question 37

what happens in defects of neural crest migration/ specification?

Answer 37

diverse birth disorders pigmentation disorders, deafness, cardiac and facial defects and failure to innervate the gut.

Question 38

what is somitogenesis?

Answer 38

segmentation of body axis formation of somites

Question 39

what do somites arise from?

Answer 39

paired blocks of paraxial mesoderm flanking the neural tube and notochord

Question 40

how do somites form?

Answer 40

* blocks of paraxial mesoderm condense and bud off in somite pairs * one of each pair on either side of the neural tube * Somitogenesis commences at the head end and progresses down the long axis of the embryo * Rate of ‘budding’ or appearance of somite pairs is species-specific, as is the number of pairs. * Humans 1 pair/90 min, 44 pairs in embryo total

Question 41

what tissues is derived from somites?

Answer 41

**sclerotome**: vertebrae and rib cartilage **dermomyotome** which subdivides to form: * dermatome: gives rise to dermis of skin, some fat and connective tissue of neck and trunk * myotome: forms the muscles of the embryo

Question 42

what does the gut arise from?

Answer 42

yolk sac (embryonic structure involved in early haematopoiesis)

Question 43

what is the yolk sac derived from?

Answer 43

hypoblast

Question 44

how is the primitive gut formed?

Answer 44

* The primitive gut arises from two types of folding in the embryo: * Ventral folding: where the head and tail ends curl together * Lateral folding: where the two sides of the embryo roll * This pinches off part of the yolk sac to form the primitive gut Primitive gut is then patterned into foregut, midgut and hindgut

Question 45

what are the derivatives of the primative gut?

Answer 45

(endoderm derived structures) * Foregut * esophagus, stomach, upper duodenum, liver, gallbladder, pancreas * midgut * lower duodenum and remainder of small intestine, ascending colon and first two-thirds of transverse colon * hindgut * last third of the transverse colon, descending colon, rectum and upper anal canal

Question 46

how is the heart formed?

Answer 46

* ​Begins as tube of mesoderm around day 19, beating and pumping blood commences around day 22 * Fetal heartbeat detectable from ~6 weeks gestational age

Question 47

how are the lungs formed?

Answer 47

* Arise from the lung bud, and endodermal structure adjacent to the foregut, in the 4^th week of development * Lung bud splits into two at the end of the 4^th week, and progressively branches through development

Question 48

how are the gonads formed?

Answer 48

* Forms from mesoderm as bipotential (i.e. not committed to testis or ovary) structures known as gonadal/genital ridges * **XY embryos:** presence of ***SRY*** gene on Y chromosome directs gonadal cells to become Sertoli cells, triggering testis development, Leydig cell formation and testosterone production * **XX embryos**: absence of *SRY* leads to gonadal cells adopting a granulosa cell fate and ovary development, requires reinforcement by *FOXL2*