Early Fetal Development

Question 1

Fertilisation age

Answer 1

Conceptual age
From time of fertilisation (assumed +1 day from last ovulation)
Difficult to know exact time unless IVF

Question 2

Gestational age

Answer 2

From beginning of last menstrual period
Determined by fertilisation date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts

Question 3

Carnegie stage

Answer 3

23 stages based on embryo features not time
Comparison of developmental rates between species
Covers window of 0-60 days fertilisation age in humans

Question 4

Maternal to zygotes transition

Answer 4

Until 4-8 cell stage, genes of embryo are not transcribed
Embryo is dependent on maternal mRNA and proteins to get through first division
The mRNA and proteins are stored and synthesised during oocyte development (pre-ovulation)
Failure to synthesise, store or interpret during oogenesis can impair embryonic development

At 4-8 cell stage between days 2 and 3 where embryonic genes take over and there is transcription of embryonic genes (zygotic genome activation). There is increased protein synthesis and organelle (mitochondria, Golgi) maturation.

Question 5

Gastrulation day 16

Answer 5

Majority of hypoblast replaced

Remaining epiblast referred to as ectoderm and forms most exterior, distal layer

Some invaginated cells remain in space between ectoderm and definitive endoderm, forming germ layer called mesoderm

Once formation is complete, there is no more invagination

Throughout, ectoderm continues to form from cranial to caudal end

Question 6

Failure of neural tube closure

Answer 6

Common developmental defect

Anencephaly - absence of most of skull and brain - failure to close at head end

Spina bifida - open neural tube at birth, usually lower spine due to failure to close tail end - varying severity

Question 7

Derivatives of primitive gut

Answer 7

Foregut - oesophagus, 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 transverse colon, descending colon, rectum and upper anal canal

Question 8

Embryogenic stage

Answer 8

From start to 14-16 days post-fertilisation
Establishing early embryo from fertilised oocyte
Determine pluripotent embryonic cells (contribute to foetus) and extraembryonic cells (contribute to support structures)
First trimester

Question 9

Embryonic stage

Answer 9

16-~50 days post fertilisation
Establish germ layers and differentiation of tissue types
Establish body plan
First trimester

Question 10

Foetal stage

Answer 10

~50-270 days post fertilisation or ~8 to ~38 weeks
Major organ systems present
Migration of some organ systems to final location
Extensive growth and acquisition of foetal viability (survival outside womb)
Second and third trimester

Question 11

First few days of life

Answer 11

Ovulated oocyte - 1 cell
Fertilisation
Zygote - 1 cell
Cleavage stage embryos - 2-8 cells
Morula - 16+ cells
Blastocyst - 200-300 cells

Occurs along migration through Fallopian tube to uterus where it is implanted
Occurs within constriction of zona pellucida (outer shell)

Question 12

Compaction

Answer 12

Around 8 cell stage or later
Outer cells pressed against zona
Change from spherical to wedge shaped
Outer cells connect through tight gap junctions and desmosomes
Form barrier to diffusion between inner and outer embryo
Outer cells become polarised with apical and basal polarity

Compacted morula gives two cell populations - inner and outer
Blastocyst is where inner cells and outer cells reorganise with formation of the blastocyst cavity. Inner cell forms clump on one said with outer cells forming blastocyst shell.

Question 13

Blastocyst formation

Answer 13

Zona pellucida - hard protein shell inhibiting polyspermy and protects early embryo
Inner cell mass - pluripotent embryonic cells
Trophoectoderm - extra embryonic cells that contribute to extraembryonic structures that support development
Blastocoel - fluid filled cavity formed osmotically by trophoblast pumping sodium ions into cavity

Question 14

Hatching

Answer 14

Day 5-6
To implant the blastocyst escapes zona pellucida
Achieved through enzymatic digestion and cellular contractions which weakens a point of zona pellucida

Question 15

Peri-implantation

Answer 15

Days 7-9

Trophoectoderm separates into syncytiotrophoblast and cytotrophoblast.
S invades uterine endometrium and starts to degrade cells of endometrium and ultimately breaks down capillaries which allows syncytiotrphoblasts to be bathed in maternal blood .
C continue to divide.

Inner cell mass separate into epiblast - from which foetal tissue will derive and hypoblast - which will form yolk sac (extraembryonic structure - important in gut development and early haematopoiesis)

Question 16

Bi-laminar embryonic disc formation

Answer 16

Day 12+

Final stage before gastrulation

Some cells become separated from epiblast by formation of new cavity - amniotic cavity
These amnion cells will contribute to extra-embryonic membranes
Leaves two layer disc of epiblast and hypoblast, sandwiched between cavities

Embryo now ready for gastrulation

Syncytiotrophoblast also start to secrete hCG - detection of beta hCG subunit in blood/urine is basis of pregnancy test

Question 17

Gastrulation day 15

Answer 17

Thickened structure form along midline in epiblast near caudal end of the disc - primitive streak - defines major body axes of embryo (cranial and caudal end, left and right side)

Streak expands to form primitive node with circular depression called primitive pit at cranial end

Depression continues along midline of epiblast toward caudal end of streak forming primitive groove

Cells migrate inwards towards the streak, detach from epiblast, and slip beneath it into interior of embryo - invagination

First cells to invaginate primitive groove invade hypoblast and displace its cells, eventually completely replaced by new proximal cell layer - definitive endoderm

Question 18

Endoderm organ relations

Answer 18

GI tract
Liver, pancreas
Lung
Thyroid

Question 19

Ectoderm organ relations

Answer 19

CNS and neural crest
Skin epithelia
Tooth enamel

Question 20

Mesoderm organ relations

Answer 20

Blood (endothelial cells, red and white blood cells)
Muscle (smooth, skeletal and cardiac)
Gonads, kidneys and adrenal cortex
Bone and cartilage

Question 21

Notochord formation

Answer 21

First event after gastrulation ~day 13+

Rod like tube structure formed of cartilage like cells

Forms from primitive streak along midline towards head end of embryo under ectoderm

Acts as a key organising centre for neurulation and mesoderm development

Controls neural plate - area of ectoderm on top of embryo - signals from notochord below ectoderm - move up through embryo and direct neural plate to form neural tube

Question 22

Neurulation

Answer 22

~day 14/15

Notochord signals direct neural plate ectoderm to invaginate forming neural groove

Creates two ridges (neural folds) running along cranio-caudal axis

Neural crest cells specified in neural folds

As development progresses neural folds move together over neural groove, ultimately fusing and forming a hollow tube

Neural tube overlaid with epidermis (ectoderm)

Migration of neural crest cells from folds and differentiate

Question 23

Closure of neural tube

Answer 23

Head end - day 23
Tail end - day 27

Closure at head end precede formation of brain structures

Question 24

Neural crest cells

Answer 24

Endoderm derived, plastic and migrate extensively through development

Question 25

Neural crest cell types

Answer 25

Cranial - cranial neurones, lower jaw, middle ear bones, facial cartilage
Cardiac - aortic arch/pulmonary artery septum, large arteries wall
Trunk - dorsal root ganglia, sympathetic ganglia, adrenal medulla, melanocytes
Vagral and Sacral - parasympathetic ganglia and enteric nervous system ganglia

Question 26

Defects of neural crest

Answer 26

Diverse range such as pigmentation disorders, deafness, cardiac and facial defects and failure to innervate gut

Question 27

Somitogenesis

Answer 27

Formation of somites - arose from paired blocks of paraxial mesoderm flanking the neural tube and notochord

Blocks of paraxial mesoderm condense and bud off in somite pairs
One of each pair either side of neural tube

Commences at head end and progresses down long axis of embryo

Rate of budding is species specific, as is number of pairs - humans - pair/90 minutes, 44 pairs total

Question 28

Somite derived tissue

Answer 28

Form two types of embryonic tissue - sclerotome and dermomyotome

S - vertebrae and rib cartilage
D - sub-divides to form dermatome (dermis of skin, some fat and connective tissues of neck and trunk) and myotome (muscles of embryo)

Question 29

Formation of gut tube

Answer 29

Day 16+

Primitive gut arises from two types of folding in embryo
Ventral - head and tail ends curl together
Lateral - two sides of embryo roll

This pinched off part of yolk sac to form primitive gut

Primitive gut is then patterned into foregut, midgut and hindgut

Question 30

Heart development

Answer 30

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 31

Lungs development

Answer 31

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

Question 32

Gonads development

Answer 32

Forms from mesoderm as bipotential (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, equites reinforcement by FOXL2