10.2 - Early Foetal Development Flashcards
1
Q
What is fertilisation age (aka conceptual age) of a foetus?
A
- time measured from time of fertilisation (assumed to be +1 day from last ovulation)
- not particularly useful, but widely used
- difficult to know time of fertilisation exactly (unless IVF)
2
Q
What is gestational age of a foetus?
A
- calculated from the time of the beginning of the last menstrual period (LMP)
- ovulation occurs 14 days into menstrual cycle and if fertilised, it signals corpus luteum to make progesterone to maintain endometrial lining
- determined by fertilisation date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts
3
Q
What is Carnegie staging system?
A
- 23 stages of embryo development based on embryo features not time
- covers the window of 0-60 days fertilisation age in humans
- allows comparison of developmental rates between species
4
Q
What three stages can we split pregnancy into based on foetal development?
A
- embryogenic stage
- embryonic stage
- foetal stage
- first trimester - embryogenic and embryonic stages
- second and third trimester - foetal stage
- transition from embryo to foetus is at the end of the first trimester going into the second
5
Q
What is the embryogenic stage?
A
- 14-16 days post-fertilisation
- establishing the early embryo from the fertilised oocyte
- results in formation of two cell types:
- pluripotent embryonic cells - contribute to foetus
- extraembryonic cells - contribute to support structures e.g. placenta
6
Q
What happens in the embryonic stage?
A
- 16-50 days post fertilisation
- establishment of germ layers and differentiation of tissue types
- establishment of the body plan
7
Q
What is the foetal stage?
A
- 8 to 38 weeks
- major organ systems now present
- migration of some organs to final location
- extensive growth and acquisition of foetal viability (survival outside the womb)
8
Q
What stages of development does the oocyte/zygote go through in the first few days of life?
A
- ovulated oocyte (1 cell)
- fertilisation –> zygote (1 cell)
- cleavage stage embryos - cell divides in 2 –> 4 –> 8
- morula (16+ cells)
- blastocyst (200-300 cells) - load of cells accumulate at one end, some surround edges, fluid centre
- occurs in the confines of the zona pellucida as the embryo moves down Fallopian tube into uterus
- only implanted in uterus after blastocyst formation
9
Q
Describe the first major embryonic developmental event - maternal-to-zygotic transition
A
- until 4-8 cell stage, genes of the embryo are not transcribed
- embryo is dependent on maternal mRNAs and proteins to get through the first divisions
- these mRNAs and proteins are synthesised and stored during oocyte development (i.e. pre-ovulation)
- in maternal-to-zygote transition, there is transcription of embryonic genes (zygotic genome activation), increased protein synthesis, and organelle (mitochondria, Golgi) maturation
- failure to synthesise, store or interpret these mRNAs and proteins during oogenesis can impair embryonic development
10
Q
Describe the second major embryonic developmental event - compaction
A
- around 8 cell stage or later, outer cells in embryo become pressed against zona pellucida and change from spherical to wedge-shaped
- they connect to each other through tight gap junctions and desmosomes
- this forms a barrier to diffusion between inner and outer embryo
- outer cells often becomes polarised
- forms a compacted morula with two distinct cell populations - inner cells shielded from external environment, and outer cells exposed
- these then develop to form a blastocyst with the formation of a blastocoel cavity
11
Q
What are the four different layers of the blastocyst?
A
- zona pellucida - hard protein shell inhibiting polyspermy and protects early embryo
- inner cell mass - pluripotent embryonic cells that will contribute to the final organism
- trophoectoderm - extra-embryonic cells that contribute to the extraembryonic structures that support development e.g. placenta (surround inside)
- blastocoel - fluid-filled cavity formed osmotically by trophoblast pumping Na+ ions into the centre of the embryo, which water follows
12
Q
What is hatching and why is it important?
A
- to implant the blastocyst, it must escape the zona pellucida
- hatching - day 5-6
- through enzymatic digestion (enzymes secreted by blastocyst) and cellular contractions, a point of the zona pellucida is weakened and the blastocyst extrudes out of the zona shell
13
Q
What happens to the trophectoderm lineage peri-implantation (day 7-9 after embryo has made first contact with endometrium)?
A
- trophectoderm lineage separates further into a syncitiotrophoblast and cytotrophoblast
- syncitiotrophoblast invades uterine endometrium and destroys local maternal cells, and breaks up capillaries to create interface between embryo and maternal blood supply
- cytotrophoblast cells remain individual to divide and provide source of syncitiotrophoblast cells
14
Q
What happens to the inner cell mass peri-implantation (day 7-9 after embryo has made first contact with endometrium)?
A
- inner cell mass separates further into:
- epiblast - from which the foetal tissues will be derived
- hypoblast - which will form the yolk sac (extraembryonic structure)
15
Q
What happens on day 12 after fertilisation?
A
- bi-laminar embryonic disc formation - final stage before gastrulation
- some epiblast cells become separated from the rest of them by the formation of an 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 (amnions –> amniotic cavity –> epiblast –> hypoblast –> blastocoel)
- epiblast goes on to form foetal structures and organs
- syncitiotrophoblasts start secreting hCG - detection of
beta-hCG subunit in blood/urine is basis of pregnancy testing - embryo ready for gastrulation
16
Q
Summary of what happens in pre and peri-implantation development
A
Embryonic:
- morula –> inner cell mass –> epiblast (–> epiblast + amnion) + hypoblast
Extra-embryonic:
- morula –> trophoblast –> cytotrophoblast + syncitiotrophoblast
17
Q
What is gastrulation?
A
The process where the bilaminar embryonic disc undergoes reorganisation to form the trilaminar disc
18
Q
What happens 15 days after fertilisation?
A
- thickened structure forms along midline of epiblast, near caudal end of bilaminar embryonic disc
- this dictates cranial and caudal ends of the embryo
19
Q
What happens to the primitive streak nearer the cranial end?
A
- expands to create a primitive node
- this contains a circular depression - the primitive pit - which continues along the midline of epiblast towards caudal end of streak, making a primitive groove
20
Q
What do epiblast cells do after primitive groove formation?
A
- migrate towards streak, detach from epiblast, and slip beneath it into interior of embryo - called invagination
- invaginating epiblast cells invade hypoblast and displace its cells
- by day 16 most of the hypoblast cells are replaced - now called the endoderm
21
Q
What is the ectoderm?
A
The remaining epiblast cells
22
Q
What becomes the mesoderm?
A
- some invaginated epiblast cells stay in space between new ectoderm and endoderm
- once mesoderm and endoderm are formed, epiblast cells no longer migrate towards primitive streak
23
Q
What structures does the endoderm give rise to?
A
- GI tract
- liver, pancreas
- lung
- thyroid
24
Q
What structures does the ectoderm give rise to?
A
- CNS and neural crest
- skin epithelia
- tooth enamel
25
Q
What structures does the mesoderm give rise to?
A
- blood - endothelial cells, RBCs, WBCs
- muscle - smooth, skeletal, cardiac
- gonads, kidneys, adrenal cortex
- bone, cartilage
26
Q
What is the notochord formation?
A
- happens on day 13+
- rod-like tube structure formed of cartilage-like cells
- forms along embryo midline (from primitive streak), under the ectoderm, and grows towards the cranial end
- acts as a key organising centre for neurulation (CNS formation) and mesoderm development
27
Q
What is the neural plate?
A
- notochord controls neural plate for neurulation
- neural plate is area of thickened ectoderm that sits on top of embryo
28
Q
How does neurulation work? (Day 15)
A
- notochord signals direct the neural plate ectoderm to invaginate forming neural groove
- this creates two ridges (neural folds) running across cranio-caudal axis
- neural crest cells become specified in neural folds
- few days later, neural folds move together over neural groove and ultimately fuse to form a hollow tube
- neural tube is overlaid with epidermis (ectoderm)
- neural crest cells from folds migrate down
29
Q
What happens to the neural tube after it is initially formed?
A
- initially open at each end
- closure at head end at day 23
- closure at tail end at day 27
- closure at head precedes formation of brain structures
30
Q
What is anencephaly?
A
- failure of neural tube closure
- absence of most of skull and brain
- arises from failure to close at the head end (1/10,000 births)
31
Q
What is spina bifida?
A
- neural tube open at birth near tail end
- usually lower spine due to failure to close tail end - varying severity
- 0.4-5/1000 births
32
Q
What are neural crest cells?
A
- ectoderm derived, plastic and migrate extensively during development
- cranial NC –> cranial neurones, glia, lower jaw, middle ear bones (ossicles), 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 NS ganglia
33
Q
What do defects in neural crest migration or specification lead to?
A
Diverse birth defects including:
- pigmentation disorders
- deafness
- cardiac defects
- facial defects
- failure to innervate gut
34
Q
What is somitogenesis?
A
- formation of somites - happens after neural tube formation
- somites arise from paired blocks of paraxial mesoderm flanking the neural tube and notochord on either side
- blocks of paraxial mesoderm condense and bud off in somite pairs
- 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
35
Q
What do somites initially divide into in terms of embryonic tissue?
A
- sclerotome - goes on to form vertebrae and rib cartilage
- dermomyotome - which in turn subdivides to form:
- dermatome - gives rise to dermis of skin, some fat and connective tissues of neck and trunk
- myotome - forms muscles of embryo
36
Q
Describe the formation of the gut tube (day 16+)?
A
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 folding pinches off part of the yolk sac to form the primitive gut
- primitive gut then patterned into: foregut, midgut, hindgut
37
Q
What does the foregut include?
A
- oesophagus
- stomach
- upper duodenum
- liver
- gallbladder
- pancreas
38
Q
What does the midgut include?
A
- lower duodenum and remainder of small intestine
- ascending colon
- first 2/3 of transverse colon
39
Q
What does the hindgut include?
A
- last 1/3 of transverse colon
- descending colon
- rectum
- upper anal canal
40
Q
How does the heart develop?
A
- begins as a tube of mesoderm around day 19
- beating and pumping commences around day 22
- foetal heartbeat detectable from 6 weeks gestational age
41
Q
How do the lungs develop?
A
- arise from lung bud, an endodermal structure adjacent to the foregut, in the 4th week of development
- lung bud splits into two at the end of the 4th week and progressively branches through development
42
Q
How do gonads develop?
A
- 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, requiring reinforcement by FOXL2, a TF essential for ovary development
