Early Fetal Development Flashcards
Fertilisation age
Conceptual age
From time of fertilisation (assumed +1 day from last ovulation)
Difficult to know exact time unless IVF
Gestational age
From beginning of last menstrual period
Determined by fertilisation date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts
Carnegie stage
23 stages based on embryo features not time
Comparison of developmental rates between species
Covers window of 0-60 days fertilisation age in humans
Maternal to zygotes transition
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.
Gastrulation day 16
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
Failure of neural tube closure
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
Derivatives of primitive gut
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
Embryogenic stage
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
Embryonic stage
16-~50 days post fertilisation
Establish germ layers and differentiation of tissue types
Establish body plan
First trimester
Foetal stage
~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
First few days of life
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)
Compaction
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.
Blastocyst formation
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
Hatching
Day 5-6
To implant the blastocyst escapes zona pellucida
Achieved through enzymatic digestion and cellular contractions which weakens a point of zona pellucida
Peri-implantation
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)
Bi-laminar embryonic disc formation
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
Gastrulation day 15
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
Endoderm organ relations
GI tract
Liver, pancreas
Lung
Thyroid
Ectoderm organ relations
CNS and neural crest
Skin epithelia
Tooth enamel
Mesoderm organ relations
Blood (endothelial cells, red and white blood cells)
Muscle (smooth, skeletal and cardiac)
Gonads, kidneys and adrenal cortex
Bone and cartilage
Notochord formation
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
Neurulation
~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
Closure of neural tube
Head end - day 23
Tail end - day 27
Closure at head end precede formation of brain structures
Neural crest cells
Endoderm derived, plastic and migrate extensively through development
Neural crest cell types
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
Defects of neural crest
Diverse range such as pigmentation disorders, deafness, cardiac and facial defects and failure to innervate gut
Somitogenesis
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
Somite derived tissue
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)
Formation of gut tube
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
Heart development
Begins as tube of mesoderm around day 19, beating and pumping blood commences around day 22
Fetal heartbeat detectable from ~6 weeks gestational age
Lungs development
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
Gonads development
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