Early fetal development Flashcards
What is fertilisation age/conceptual age?
- measured from time of fertilisation (assumed to be 1 day after last ovulation, as generally fertilisation has to occur w/in 24h of ovulation)
- weeks or days post-fertilisation
- difficult to know time of fertilisation exactly unless IVF
What is gestational age?
- calculated from the time of the beginning of the last menstrual period
- determined by early obstetric ultrasound comparing to embryo size charts
- always 14 days longer than fertilisation age bc it goes from start of menstrual period rather than point of ovulation or fertilisation
What is the Carnegie staging system?
- 23 stages of embryo development based on embryo FEATURES, not time
- allows comparison of developmental rates between species
- covers window of 0-60 days post-fertilisation in humans
What is the embryogenic stage?
- runs from point of fertilisation to about 14/16 days post fertilisation
- early embryo established from fertilised oocyte
- characterised by formation of 2 cell types: pluripotent embryonic cells- contribute to foetus, and extra embryonic cells- contribute to support structures e.g. placenta
What is the embryonic stage?
- runs from about 16 days post-fertilisation to about 50 days post fertilisation
- establishment of germ layers and differentiation of tissue types
- establishment of body plan
What is the foetal stage?
- runs from about 50 days to 270 days post fertilisation (~8-~38 weeks)
- major organ systems now present, although some may be in different place
- migration of some organ systems to final location
- extensive growth and acquisition of fetal viability (ability to survive outside womb)
What stages correspond to the first trimester?
embryogenic and embryonic stages
What stage corresponds to the second and third trimesters?
foetal stage
so transition from embryo–> foetus occurs roughly at end of 1st trimester
What happens in the first few days of life?
- ovulated oocyte, single cell
- undergoes fertilisation–> becomes zygote
- undergoes mitotic divisions–> cleavage stage embryos 2-4-8 cell embryo
- further divisions–> morula (16+ cells)
- progresses to form blastocyst (200-300 cells)
- all happens as it migrates along Fallopian tube into uterus
N.B. zona pellucida present for all these stages^
What is the maternal-to-zygotic transition?
- occurs at 4-8 cell stage
- before this, none of the genes in the embryo are transcribed and the development/division is dependent on maternal mRNAs and proteins
- these mRNAs and proteins are synthesised and stored during oocyte development (before ovulation)
- at transition, embryonic genes get transcribed, increased protein synthesis, and maturation of organelles e.g. mitochondria and Golgi
What is compaction?
- occurs around 8-cell stage or later
- gives first 2 cell types (inner and outer)
- outer cells become pressed against zone pellucida–> change from spherical to wedge-shaped
- tight junctions and desmosomes form between these outer cells, connecting them and forming a barrier to diffusion between inner and outer embryo
- outer cells also become polarised (apical and basal)
What is the role of the zona pellucida?
- protect early embryo
- prevent polyspermy
What is the structure of the blastocyst?
- contained w/in zona pellucida
- inner cell mass (from inner cells): gives rise to pluripotent embryonic cells that will contribute to final organism
- trophectoderm (from outer cells): gives rise to extra-embryonic cells that contribute to extra embryonic structures that support development e.g. placenta
- blastocoel: fluid-filled cavity formed osmotically by trophoblasts pumping Na+ ions into centre of embryo (water then follows)
What is hatching?
- around day 5-6
- blastocyst secretes enzymes and cellular contractions weaken a point in the shell
- -> blastocyst escapes from the zona pellucida shell
- blastocyst can now implant in endometrium
What differentiation events occur when the embryo has undergone its initial connection with the endometrium (peri-implantation events ~day 7-9)?
- trophectoderm lineage separates into syncitiotrophoblasts and cytotrophoblasts
- sycitiotrophoblast is invasive–> invades endometrium and degrades local maternal cells, breaking down capillaries–> so syncitiotrophoblasts are bathed in maternal blood
- cytrotrophoblast cells continue to divide to provide more syncitiotrophoblast cells - inner cell mass separates into epiblasts and hypoblasts
- epiblasts will form foetal tissues
- hypoblasts will form yolk sac (extraembryonic structure)
When does bi-laminar embryonic disc formation occur?
around day 12 post fertilisation
What occurs during bi-laminar embryonic disc formation?
- some epiblast cells separate from main block, forming the amniotic cavity–> epiblast cells along the top give rise to the amnion (an extra-embryonic membrane)–> whereas the epiblasts below the amniotic cavity give rise to foetal structures/organs
- hypoblast remains sitting under the epiblast (the one below amniotic cavity)–> 2-layer disc of epiblast+hypoblast, in the middle between cavities - BI-LAMINAR EMBRYONIC DISC
- now ready for gastrulation
What cells secrete hCG?
syncitiotrophoblasts secrete hCG (detection of beta hCG subunit in blood/urine = pregnancy test)
When does gastrulation occur?
during the 3rd week post-fertilisation
What is the process of gastrulation?
- generation of 3 primary germ layers
- around 15 days post-fertilisation, a thickened structure forms along midline in epiblast near caudal end of bilaminar embryonic disc–> primitive streak
- at cranial end, primitive streak expands to create primitive node, containing primitive pit (circular depression)–> then forms primitive groove
- epiblast cells migrate inwards towards primitive groove and slip beneath it (invagination), invading hypoblast and displacing its cells–> becomes definitive ENDODERM
- by day 16, majority of hypoblast= replaced and remaining epiblast cells = ECTODERM, forming most exterior/distal layer
- some invaginated epiblast cells remain in space between ectoderm + definitive endoderm–> form germ layer MESODERM
- ectoderm continues to form from cranial to caudal end of embryo until 3 distinct primary germ layers exist throughout whole embryonic disc–> TRILAMINAR DISC
What organs/systems does the endoderm give rise to?
- GI tract
- liver
- pancreas
- lung
- thyroid
What organs/systems does the ectoderm give rise to?
- CNS and neural crest
- skin epithelia
- tooth enamel
What organs/systems does the mesoderm give rise to?
- blood (endothelial cells, red and white blood cells)
- muscle (smooth, skeletal and cardiac)
- gonads, kidneys and adrenal cortex
- bone and cartilage
What is the notochord and its role?
- rod-like tube structure formed by cartilage-like cells and substances
- forms from primitive streak, underneath ectoderm, growing towards cranial end along the embryo midline
- acts as key ORGANISING centre for embryonic development: releases GF signals important for neurulation (CNS formation) and mesoderm development esp. muscles
What is the neural plate and its role?
- area of thickened ectoderm sits on top of embryo
- signals from notochord (beneath ectoderm) move up through embryo and direct neural plate to form neural groove (neurulation)
What is neurulation?
- formation of neural tube and CNS
- notochord signals neural plate to invaginate–> forming neural groove
- creates 2 ridges (neural folds), running along cranio-caudal axis
- neural crest cells are in neural folds
- then neural folds move together over neural groove–> meet and fuse, forming a hollow tube (neural tube)
- meanwhile neural crest cells migrate away from neural folds and populate various tissues, differentiating as they go
What needs to happen to the neural tube for CNS development to precede?
neural tube needs to be closed at both the head and tail end
head end closes first
What is spina bifida?
- developmental defect
- open neural tube at birth
- usually lower spine due to failure to close tail end
- varying severity
What is anencephaly?
- developmental defect
- absence of most of skull and brain
- failure to close neural tube at the head end
What structures do cranial neural crest cells give rise to?
- middle ear bones (ossicles)
- cranial neurones and glia
- lower jaw
- facial cartilage
What structures do cardiac neural crest cells give rise to?
- aortic arch
- pulmonary artery septum
- large arteries wall musculoconnective tissue
What structures do trunk neural crest cells give rise to?
- dorsal root ganglia
- sympathetic ganglia
- adrenal medulla
- aortic nerve clusters
- melanocytes
What structures do vagal and sacral neural crest cells give rise to?
- parasympathetic ganglia
- enteric nervous system ganglia
What happens when neural crest cells can’t form or migrate normally during embryonic development?
leads to diverse birth defects including pigmentation disorders, deafness, cardiac and facial defects, and failure to innervate the gut
What is somitogenesis?
- formation of somites
- blocks of paraxial mesoderm condense and bud off in somite pairs
- formation of somites starts at head end of embryo and works down towards tail end
- rate of budding and number of paired blocks are species specific
- 44 pairs of somites in human embryo and 1 pair formed per 90min
What 2 different tissue types do somites initially divide into?
- sclerotome
- dermomyotome
What does the sclerotome give rise to?
vertebrae and rib cartilage
What does the dermomyotome give rise to?
- dermatome: contributes to dermis of skin, some fat and connective tissue of neck and trunk of embryo
- myotome: forms muscles of embryo
What 2 types of folding give rise to the primitive gut and what occurs during these processes?
- ventral folding: head and tail of embryo fold inwards
- lateral folding: the 2 sides of embryo fold in
–> these processes pinch off part of the yolk sac to form the primitive gut, which is then organised into foregut, midgut and hindgut
What does the foregut give rise to?
- oesophagus
- stomach
- upper duodenum
- liver
- gallbladder
- pancreas
^endoderm derived
What does the midgut give rise to?
- lower duodenum and remainder of small intestine
- ascending colon and first 2/3 or transverse colon
What does the hindgut give rise to?
- last 1/3 of transverse colon
- descending colon
- rectum
- upper anal canal
When and how does the heart form?
- forms as a tube of mesoderm around day 19
- beating and pumping blood starts around day 22
- foetal heartbeat detectable from ~6 weeks gestational age
When and how do the lungs form?
- endodermal structure
- arise from lung bud, which is adjacent to foregut
- lung bud starts to arise around 4th week of development then splits into 2 at end of 4th week then progressively branches–> bronchi and bronchioles
When and how do the gonads form?
- form from mesoderm as originally bipotential structures (not committed to testis or ovary) called gonadal/genital ridges
- in 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
- in XX embryos, absence of SRY gene leads to gonadal cells adopting granulosa/ovarian cell fate–> reinforced by transcription factor FOXL2- essential for ovary development
