early foetal development Flashcards
how do we measure time in embryo-foetal development?
fertilisation age - from ovulation +1
gestational age - from beginning of last period
carnegie age - based on embryological features
or dividing into stages based on development
what is fertilisation age?
measured from the time of fertilisation
assumed to be +1 day from last ovulation (fertilisation generally has to occur in this window)
difficult to know exact time of fertilisation unless IVF
usually expressed in weeks post ovulation or days post ovulation
not particularly practical
what is gestational age?
calculated from the time of the start of the last menstrual period
determined by fertilisation date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts
(it is always 14 days longer than fertilisation age)
what is carnegie age?
23 stages of embryo development based on embryo features not time
allows comparison of developmental rates between species
covers the window of 0-60 days fertilisation age in humans
what are the stages of embryo development used in measuring time in embryo foetal development?
- embryogenic stage
- embryonic stage
- fetal stage
1 and 2 are in the 1st trimester ( first 12 weeks)
3 is second and third trimester
so embryo becomes foetus at roughly the end of the first trimester
what is the embryogenic stage?
1-14/16 days post fertilisation
establishing the early embryo from the fertilised oocyte
determining two populations of cell types: pluripotent embryonic cells (contribute to foetus) extraembryonic cells (contribute to the supporting structures eg. placenta)
what is the embryonic stage?
16- 50 days post fertilisation
establishment of the germ layers and differentiation of tissue types
establishment of the body plan
what is the fetal stage?
50 - 270 days post fertilisation
major organ systems now present but not in the right place
migration of some organ systems to final location
extensive growth and acquisition of fetal viability (ability to survive outside the womb)
what happens in the first few days of life?
ovulated oocyte (1 cell) ->
fertilisation with sperm (2 cells)->
becomes zygote (one cell) ->
cleavage divisions to become cleavage stage embryos (2-8 cells) ->
further mitotic divisions to form morula (16+ cells) ->
blastocyst (200-300 cells)
during this process the embryo is migrating along the fallopian tube so it can reach the uterus and implant
zona pellucida is present in all of these stages
what is the maternal to zygotic transition?
first major developmental event
occurs at the 4-8 cell stage
UNTIL this stage the genes of the embryo are not transcribed
the embryo is dependant on maternal mRNAs and proteins to get through the first divisions
these mRNA and proteins are synthesised and stored during oocyte development (pre ovulation)
failure to synthesise, store or interpret these during oogenesis can impair embryonic development
in the maternal-to-zygotic transition:
transcription of embryonic genes (zygotic genome activation)
increased protein synthesis
organelle (mitochondria, golgi) maturation
what is compaction?
the second major developmental event
starts formation of the first two cell types
around the 8 cell stage or later
outer cells become pressed against the zona pelllucida
the change from spherical to wedge shaped
outer cells connect to each other through tight gap junctions and desmosomes
this forms a barrier to diffusion between the inner and outer embryo
the outer cells become polarised
compacted morula:
has two cell types - inner and outer
later these will develop further in the blastocyst, with the outer cells forming a shell and the inner cells forming a clump at one end of the blastocyst
what are the cells present in the early blastocyst?
inner cell mass:
pluripotent embryonic cells that will contribute to the final organism
trophectoderm (cells round the outside):
extra-embryonic cells that contribute to the extraembryonic structures that support development
blastocoel:
fluid filled cavity formed osmotically by trophobalst pumping Na+ ions into cavity
these are enclosed in the zona pellucida:
inhibits polyspermy
protects the early embryo
what is hatching?
occurs around day 5-6
the escape of the blastocyst from the zona pellucida
this allows the blastocyst to implant
happens via:
enzymatic digestion
cellular contractions
this leaves the empty zona pellucida
this is vital for the blastocyst to implant
what happens during peri-implantation events?
around day 7-9
embryo has undergone initial connection with the endometrium
the trophectoderm (outer cells) lineage separates further: trophoblast cells fuse to form syncitiotrophoblast
sincitiotrophoblast invasion destroys local maternal cells in the endometrium
this creates interface between embryo and maternal blood supply
cytotrophoblast cells remain individual to provide a source of syncitiotrophoblast cells
inner cell mass:
epiblast - from which the fetal tissues will be derived
hypoblast - which will form the yolk sac (extraembryonic structure)
what are the lineages of embryonic cells by about day 9?
morula ->
splits into inner cell mass and trophoblast
inner cell mass ->
epiblast and hypoblast
trophoblast ->
cytotrophoblast and syncitiotrophoblast
what is bi-laminar embryonic disc formation?
day 12+
the bilayer embryonic disc is the final stage before gastrulation
the syncitiotrophoblast continues to expand into the endometrium
some of the epiblast cells become separated from the epiblast by the formation of a new cavity - the amniotic cavity
these amnion cells will contribute to the extra-embryonic membranes
this leaves a two layer disc of epiblast and hypoblast, sandwiched between cavities (amniotic and blastocoel)
the embryo is now ready for gastrulation
what does the syncitiotrophoblast do during formation of the bi-laminal embryonic disc?
secretes hCG
detection of beta hCG subunit in blood/urine is basis of pregnancy testing
what is the process of gastrulation?
when the three germ layers are created
formation of the primitive streak defines head and tail and left and right axes of the embryo
invagination of cells into the primitive streak forms 3 germ layers:
endoderm - first through streak (where the hypoblast cells were)
mesoderm - sandwiched between endo and ecto
ectoderm - remains on the upper, ventral surface (where the epiblast cells were)
what are the embryonic cell lineages after gastrulation?
morula ->
forms inner cell mass and trophoblast
trophoblast ->
form cytotrophoblast and syncitiotrophoblast
inner cell mass ->
forms epiblast and hypoblast
epiblast ->
forms ectoderm, mesoderm and endoderm
what body parts does the endoderm give rise to?
GI tract
liver, pancreas
lungs
thyroid
what body parts does the ectoderm give rise to?
CNS and neural crest
skin epithelia
tooth enamel
what body parts does the mesoderm give rise to?
blood (endothelial cells, red and white blood cells)
muscle (smooth, skeletal, cardiac)
gonads, kidneys and adrenal cortex
bone, cartilage
what is notochord formation?
day 13+
notochord is a rod like tube structure formed of cartilage like cells
it forms along the embryo midline, under the ectoderm
grows from the head end of the primitive streak towards the head end of the embryo
it acts as a key organising centre for embryonic development, providing growth factor signals for:
neurulation (CNS formation)
mesoderm development
what is the neural plate?
how the notocord organises neurulation
it is an area of ectoderm that sits on top of the embryo.
signals from the notocord below the ectoderm, move up through the embryo and direct the neural plate to form something called the neural tube
what is first part of neurulation?
around day 14/15
forming the neural tube and CNS
the notocord sends signals to the neural plate to do two things:
1. for part of the neural plate to invaginate and move down towards the notocord, creating the neural groove
- for two areas of the neural plate to move upwards, crating two crests, called the neural fold. these are ridges that run along the cranial caudal axis of the embryo
within the neural folds are neural crest cells
what is the second part of neurulation?
a couple of days later (16/17)
the neural folds move upwards and towards each other
they will eventually meet in the middle and fuse
this creates a sealed lid over the top of the neural groove. this forms the neural tube (originally made from neural plate)
this is overlaid with epidermis (ectoderm)
the neural crest cells also migrate, forming folds
when does the neural tube close?
has to close for further neural development to proceed
closure at head and ~day 23
closure at tail end ~ day 27
the closure at head end precedes formation of brain structures
what happens if the neural tube fails to close?
anencephaly:
absence of most of skull and brain
arises from failure to close at the head end
1/10000 births
spina bifida: open neural tube at birth usually open in lower spine due to failure to close tail end varying severity 0.4-5/1000 births
what are neural crest cells and their types?
ectoderm derived
highly plastic and highly migratory, to throughout the embryo
can be classified according to where they end up:
cranial NC - cranial neurones, glia, lower jaw, middle ear bones, facial cartilage
cardiac NC - aortic arch/pulmonary artery septum, large arteries wall musculoconnective tissue
trunk NC - dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters, melanocytes
vagral and sacral NC - parasympathetic ganglia and enteric nervous system ganglia
defects of neural crest migration/specification lead to diverse birth defects:
eg. pigmentation disorders, deafness, cardiac and facial defects, failure to innervate the gut
what is somitogenesis?
formation of somites:
arises from paired blocks of paraxial mesoderm flanking the neural tube and notochord
blocks of paraxial mesoderm condense and bud off in somite pairs, on each 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 and number of pairs is species specific
humans: 1 pair/90 mins, 44 pairs
what are somite derived tissues?
somites initially form two types of embryonic tissue:
sclerotome - vertebrae and rib cartilage
dermomyotome - sub divides more:
dermatome: gives rise to the dermis of the skin, some fat and connective tissues of neck and trunk
myotome: forms the muscles of the embryo
how does formation of the Gut tube work?
happens at day 16+
arises from the yolk sac, which is derived from hypoblast
the primitive gut arises from 2 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
what are the derivatives of the primitive gut?
(endoderm derived structures)
foregut:
oesophagus, stomach, upper duodenum, liver, gall bladder, pancreas
midgut:
lower duodenum, jejunum, ileum, ascending colon, first two thirds of transverse colon
hindgut:
last third of the transverse colon, descending colon, rectum and upper anal canal
how is the heart formed?
mesodermal derived
begins as tube of mesoderm around day 19
beating and pumping of blood begins around day 22
foetal heartbeat detectable from around 6 weeks gestational age
how are the lungs formed?
endodermal structure
arise from the lung bud, just adjacent to the foregut
in the fourth week of development
lung bud splits into two at the end of the fourth week, and progressively branches through development
how do the gonads form?
mesodermal
initially bipotential ( not committed to testes or ovaries) 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
