Early Foetal Development Flashcards
How do you measure Fertilisation age?
measured from the time of fertilization (assumed to be +1 day from last ovulation)
difficult to know time of fertilization exactly (unless IVF)
How do you measure Gestational Age?
Determined by fertilization date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts.
Calculated from the time of the beginning of the last menstrual period
How do you calculate the Carnegie stage?
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 fertilization age in humans
What are the periods of the first Trimester?
Embryogenic stage
Embryonic stage
Which period forms the second & third trimester?
Fetal stage
What happens in the embryogenic stage?
14-16 days post-fertilization):
establishing the early embryo from the fertilized oocyte
Determining two populations of cells: pluripotent embryonic cells (contribute to fetus)
Extraembryonic cells (contribute to the support structures eg placenta
What happens in the Embryonic stage?
Establishment of the Germ layers & differentiation of tissue types.
Establishment of the body plan
What happens in the Fetal stage?
Major organ systems now present
Migration of some organ systems to final location
Extensive growth and acquisition of fetal viability (survival outside the womb)
What happens in the first few days of life?
Ovulated oocyte fertilised by sperm, forms zygote.
Zygote undergoes a series of cleavage divisions, giving a 2, 4 ,8 (cleavage embryos).
8 Cell embryo proceeds with further mitotic divisions giving us the Morula (16+ cells).
Morula progresses to form Blastocyst (200-300 cells).
What is happening genetically at the 4 -8 cell stage?
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.
What happens in the Maternal to zygotic transition?
Transcription of embryonic genes (zygotic genome activation)
Increased protein synthesis
Organelle (mitochondria, Golgi) maturation
What happens during compaction?
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
What cell types are created by compaction?
Inner cell & outer cell. Outer cells form shell of blastocyst, inner cells form clump at inner blastocyst
What is the role of the Zone Pellucida?
Hard protein shell inhibiting polyspermy and protects early embryo
What do the inner cell mass in the blastocyst give rise to?
Pluripotent embryonic cells that will contribute to the final organism
What do the outer cells (Trophoectoderm) in the blastocyst give rise to ?
Extra-embryonic cells that contribute to the extraembryonic structures that support development
What is the Blastocoel?
Fluid-filled cavity formed
osmotically by
trophoblast pumping
Na+ ions into cavity
What happens in Hatching?
Hatching (day 5-6):
To implant the blastocyst must escape zona pellucida.
Enzymatic digestion
Cellular contractions
What happens 7-9 days post implantation in the Trophectoderm lineage?
Trophoectoderm lineage separates further:
trophoblast cells fuse to form syncitiotrophoblast
Syncitiotrophoblast invasion destroys local maternal cells in the endometrium
Creates interface between embryo and maternal blood supply
cytotrophoblast cells remain individual to provide source of syncitiotrophoblast cells
What happens to the inner cell lineage at days 7-9?
Inner cell mass separates further into:
epiblast: from which the fetal tissues will be derived.
hypoblast: which will form the yolk sac (extraembryonic structure)
When does Bi-laminar embryonic disc formation occur?
day 12
What happens in Bi-laminar embryonic disc formation?
final stage before gastrulation
Some 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.
Embryo is now ready for gastrulation
What underpins pregnancy testing?
Syncitiotrophoblast secretes hCG
Detection of beta hCG subunit in blood/urine is basis of pregnancy testing
What happens at day 15?
at 15 days - thickened structure forms in the midline of the epiblast (Primitive streak)
Primitive streak defines body axis, cranial + caudal, left + right sides of embryo.
Primitive node contains primitive pit, forms groove
epiblast cells migrate inwards towards streak, detach from epiblast and slip beneath it into embryo anterior - invagination
What happens at day 16?
16 - Hypoblast cells are replaced by a new layer known as a definitive endoderm, remaining cells of epiblast are known as the ectoderm.
some of the epiblast cells that had migrated previously under the epiblast form the mesoderm
once formation of layers is complete epiblasts no longer migrate towards primitive streak
What do the cells of the Endoderm Give rise to?
GI Tract, Liver, Pancreas, Lung, Thyroid
What do the cells of the Ectoderm give rise to?
CNS + Neural crest
Skin epithelia
Tooth enamel
What do the cells of the Mesoderm give rise to?
Blood
Muscle
Gonads, Kidneys, adrenal cortex
Bone, cartilage
What is the first major event after Gastrulation?
Notochord is a rod-like tube structure formed of cartilage-like cells
Forms along the embryo midline, under the ectoderm
Day 13
What is the role of the Notochord?
Acts as a key organizing centre for neurulation and mesoderm development
How do the neural folds form?
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
How is the neural tube formed?
Neural folds move together over neural groove
Ultimately neural folds fuse, forming a hollow tube
Neural tube overlaid with epidermis (ectoderm)
Migration of the neural crest cells from folds
When does neural tube closure occur?
Neural tube initially open at each end
Closure at head end: ~ d23
Closure at tail end: ~ d27
Why is neural tube closure important?
Closure at head end precedes formation of brain structures
What are some failure of neural tube closure development defects?
Anencephaly (absence of most of the skull and brain) arises from failure to close at the head end (1/10,000 births)
Spina bifida (open neural tube at birth, usually lower spine due to failure to close tail end– varying severity – (0.4-5/1000 births)
Where do neural crest cells come from?
Ectoderm-derived, plastic and migrate extensively during development:
How do we classify Neural crest cells?
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 & Sacral NC: parasympathetic ganglia and enteric nervous system ganglia
What do neural crest migration failures lead to?
Defects of neural crest migration/specification lead to diverse birth defects including pigmentation disorders, deafness, cardiac and facial defects and failure to innervate the gut.
What is somitogenesis?
Formation of somites, segmentation of the body axis
What are somites?
arise from paired blocks of paraxial mesoderm flanking the neural tube and notochord
How does Somitogenesis take place?
Blocks of paraxial mesoderm condense and bud off in somite pairs
One of each pair 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
When does human somitogenesis end?
When we have reached 44 pairs
What are the types of tissue that somites divide into?
Sclerotome
Dermomyotome
What does the Sclerotome develop into?
Vertebrae + Rib cartilage
What does the Dermomyotome develop into?
in turn sub-divides to form:
Dermatome: gives rise to dermis of the skin, some fat and connective tissues of neck and trunk
Myotome: forms the muscles of the embryo
What is the yolk sac?
Embryonic structure involved in early Haematopoesis.
Derived from hypoblast
How does the primitive gut form?
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.
What is the primitive gut further organised into?
Foregut
Midgut
Hindgut
What does the Foregut give rise to?
esophagus, stomach, upper duodenum, liver, gallbladder, pancreas
What does the Midgut give rise to?
Lower duodenum & remainder of small intestine, ascending colon & first two thirds of transverse colon
What does the Hindgut give rise to?
Last third of the transverse colon, descending colon, rectum & upper anal canal
How does the Heart develop?
Begins as tube of mesoderm around day 19, beating and pumping blood commences around day 22
Fetal heartbeat detectable from ~6 weeks gestational age
How do the lungs develop?
Arise from the lung bud, and 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
How do the Gonads develop?
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
