EARLY FETAL DEVELOPMENT Flashcards
What are the different ways of measuring time in embryo-fetal development?
Fertilisation age
Gestational age
Carnegie stage
How is fertilisation age measured?
From time of fertilisation (assume +1 day from last ovulation)
Difficult to know time of fertilisation exactly
How is gestational age measured?
Calculated from time of the beginning of the last menstrual period
Fertilisation date + 14 days if known
or
Early obsetric US and comparison to embryo size charts
How is carnegie age measured?
23 stages of embryo development based on embryo features not time
Allows comparison of developmental rates between species
What stages of development does the embryo/fetus go through in the first trimester?
Embryogenic stage
Embryonic stage
How long is a trimester?
12 weeks
What stage of development does the embryo/fetus go through in the second and third trimester?
Fetal stage
What occurs in the embryogenic stage?
Establish early embryo from fertilised oocyte
Determine the 2 populations of cells:
- Pluripotent embryonic cells (contribute to fetus)
- Extraembryonic cells (contribute to support structures)
What occurs in the embryonic stage?
Establish germ layers and differentiation of tissue types
Establish body plan
What occurs in the fetal stage?
Major organ systems present
Migration of organ systems to final location
Extensive growth and acquisition of fetal viability
As the ovulated oocyte develops what are the names given to it?
Ovulated oocyte (1 cell) Fertilisation Zygote (1 cell) Cleavage stage embryos (2-8 cells) Morula (16+ cells) Blastocyst (200-300 cells)
At what point do the genes of embryo start being transcribed and what is this called?
4-8 cell stage
Zygotic genome activation
How does the embryo get its mRNA and proteins for its first few divisions?
Dependent of maternal mRNA and proteins
Synthesised and stored during oocyte development
How do the 2 cell populations come about?
Around 8 cell stage or later:
- Outer cells compacted against zona pellucida causing
change from spherical to wedge shape
- Outer cells connect each other with tight gap junctions
and desmosomes
- Diffusion barrier formed between inner and outer cells
- Outer cells become polarised
Describe the structure of the blastocyst
Zona pellucida enveloping early embryo
Trophoectoderm layer underneath zona
Inner cell mass on one side of embryo
Blastocoel on other side
What is the inner cell mass made of?
Pluripotent embryonic cells which contribute to final organism
What is the trophoectoderm made of?
Extra-embryonic cells which contribute to extra-embryonic structures that support development e.g. placenta
What is the blastocoel and what is it made of?
Fluid filled cavity formed osmotically by trophoblast pumping Na+ ions into cavity
What is hatching and when does it occur?
Day 5-6 the development potential becomes limited by zone pellucida so embryo undergoes hatching:
Blastocyst escapes the zona pellucida by enzymatic digestion and cellular contractions to implant
What are the peri-implantation events (around day 7-9)?
Trophoblasts of trophoectoderm fuse to form syncitiotrophobast
Syncitiotrophobast invades endometrium destroying maternal cells creating embryo and maternal blood supply interface
Cytotrophoblast cells don’t fuse and remain around embryo to provide source of syncitiotrophobast cells
Inner cell mass separates into:
- Epiblast (fetal tissue derived from this)
- Hypoblast (forms yolk sac)
What is the final stage before gastrulation?
Bilaminar embryonic disc formation
Describe the process of bilaminar embryonic disc formation (day 12+)
Amniotic cavity forms splitting the epiblast.
Cells above the cavity called amnion cells.
Bilaminar embryonic disc (epiblast + hypoblast) is formed and is sandwiched between amniotic cavity and blastocoel
What do amnion cells do?
Contribute to extra-embryonic membranes
From day 12+ (bilaminar disc formation) what do the syncitiotrophoblasts secrete?
hCG which can be detected in blood/urine for pregnancy testing
At what time point does gastrulation occur?
3rd week of development
What does the process of gastrulation achieve?
Bilaminar disc differentiation into 3 primary germ layers
Describe the process of gastrulation
PRIMITIVE STREAK forms
At cranial end, primitive streak expands forming PRIMITIVE NODE which has a circular depression - PRIMITIVE PIT
At caudal end, PRIMITIVE GROOVE formed
INVAGINATION occurs, epiblast cells invade and the hypoblast cells are displaced and replaced forming DEFINITIVE ENDODERM
Remaining cells in the epiblast now called ECTODERM
Some invaginated epiblast cells remain in space between ectoderm and endoderm to form a germ layer - MESODERM
Epiblast cells stop migrating towards primitive streak
Throughout gastrulation, ectoderm continues to form from cranial to caudal end establishing 3 distinct primary germ layers throughout embryonic disc
How many days after fertilisation does the primitive streak form?
15 days after fertilisation
What is the primitive streak?
Thickened structure along midline of epiblast which defines the major body axes of the embryo (cranial/caudal, left/right)
How does the primitive groove form?
At caudal end, cells of epiblast migrate inwards towards the streak and detach from epiblast and slip beneath it into the interior of the embryo - invagination
What organs does the endoderm form?
GI tract Liver Pancreas Lung Thryoid
What does the ectoderm form?
CNS and neural crest
Skin epithelia
Tooth enamel
What does the mesoderm form?
Blood Muscle Gonads Kidneys Adrenal cortex Bone Cartilage
When does the notochord form?
Around day 13+
First major event after gastrulation
What is the notochord and its function?
Rod-like tube structure formed of cartilage-like cells along the embryo midline under ectoderm
Acts as a key organising centre for neurulation and mesoderm development
What is goal of neurulation?
Forming the neural tube and CNS
What is the neural plate?
Thickened ectoderm which sits on top of embryo serving as the basis for the nervous system
Describe the process of neurulation
Notochord signals direct neural plate to invaginate forming neural groove
Forms 2 ridges (neural folds) along cranio-caudal axis
Neural crest cells specialise in neural folds
Neural folds move together over neural groove and fuse forming neural tube
Neural tube is overlaid with epidermis (ectoderm)
Neural crest cells in folds migrate with it
Neural tube is initially open at each end:
- head end closes ~day 23 before formation of brain
structures
- tail end closes ~day 27
What defects can arise from failure of neural tube closing?
Anencephaly - failure to close head end causing absence
of most of skull and brain
Spina bifida - open neural tube at birth usually lower spine affected due to failure to close tail end
What do the cranial neural crest cells form?
Cranial neurones Glia Lower jaw Ossicles Facial cartilage
What do the cardiac neural crest cells form?
Aortic arch/pulmonary artery Septum Large arteries Musculoconnective tissue Walls of heart
What do the trunk neural crest cells form?
Dorsal root ganglion Sympathetic ganglia Adrenal medulla Aortic nerve clusters Melanocytes
What do the vagral and sacral neural crest cells form?
PNS ganglia
Enteric nervous system ganglia
List the derivatives of neural crest cells
Cranial NC
Cardiac NC
Trunk NC
Vagral and sacral NC
What is somitogenesis?
Formation of somites to segment the body axis
Describe the process of somitogenesis
Blocks of paraxial mesoderm condense and bud off in somite pairs flanking the neural tube and notochord
Starts at head end and progresses down to long axis of embryo
Rate of budding and number of pairs is species specific
What is the rate of budding in somitogenesis for humans?
1 pair/90 min
How many pairs of somites do humans have?
44 pairs
What are the two initial types of embryonic tissue formed from somites?
Sclerotome: vertebrae and rib cartilage
Dermomyotome:
- Dermatome (dermis of skin, fat and connective tissues of
neck and trunk)
- Myotome (muscles of embryo)
When does the formation of the gut tube occur?
Day 16+
How does the primitive gut form?
Arises from 2 types of folding in embryo:
- Ventral folding (head and tail ends curl together)
- Lateral folding (two sides of the embryo roll)
The folding pinches off part of the yolk sac to form the primitive gut
What does the primitive gut go on to form?
Foregut, midgut and hindgut
Where is the yolk sac derived from?
Hypoblast
What does the foregut go on to form?
Oesophagus Stomach Upper duodenum Liver Gallbladder Pancreas
What does the midgut go on to form?
Lower duodenum and remaining small intestine
Ascending colon
First 2/3 of transverse colon
What does the hindgut go on to form?
Last 1/3 of transverse colon
Descending colon
Rectum
Upper anal canal
What are the developmental landmarks of the heart?
Begins as tube of mesoderm ~ day 19
Beating and pumping blood ~ day 22
Fetal heartbeat detectable ~ 6 weeks gestation age
What are the developmental landmarks of the lung?
Arises from lung bud and endodermal structure adjacent to foregut ~ 4th week of development
Lung bud splints into 2 at end of 4th week and progressively branches through development
What are the developmental landmarks of the gonads?
Forms from mesoderm as bipotential gonadal/genital ridges
XY embryos: SRY gene on Y chromosome directs gonadal cells to become sertoli cells triggering testis development, leydig cell formation and testosterone pro
XX embryos: No SRY gene means gonadal cells adopt a granulosa cell fate and ovary development.
Requires FOXL2 reinforcement
Draw out the embryonic cell lineage
Page 18 of notes
