Early foetal development + disorders Flashcards
what is fertilisation age?
measured from the time of fertilisation (assumed +1 day drom last ovulation)
often difficult to measure unless IVF
what is gestational age?
calculated from the time of the beginning of the last menstrual period
determined by fertilisation date (+14 days) or early obstetric ultrasound and comparison to embryo size charts
what are carnegie stages?
23 stages of embryo development based on embryo features (not time)
allows comparison of developmental rates between species
covers window of 0-60 days fertilisation age in humans
when is the embryogenic stage of pregnancy?
14-16 days post fertilisation
what occurs within the embryogenic stage of pregnancy?
establishing the early embryo from the fertilised oocyte
pluripotent embryonic and extraembryonic cells established
what is the embryonic stage of pregnancy?
16-~50 days post fertilisation
establishing germ layers
what occurs within the embryonic stage of pregnancy?
establishment of germ layers, body plan and differentiation of tissue types
how long is the first trimester and what stages make this up?
~12wks
embryogenic and embryonic stages
what is the fetal stage of pregnancy?
~8wks to ~38wks post fertilisation
what occurs within the fetal stage of pregnancy?
major organ systems now present
migration of some organ systems to final location
extensive growth and acquisition of fetal vitality (survival outside the womb)
what cell cluster occurs after zygotic cleavage?
cleavage stage embryos (2-8 cells)
what cell cluster occurs after cleavage stage embryos?
morula (16 cells)
what cell cluster occurs after a morula?
blastocyst (200-300 cells)
when does the maternal-to-zygotic transition occur?
4-8 cell stage aka as a morula
this is zygotic genome activation
around 2 days after fertilisation
what is zygotic genome activation?
where the embryo transitions from being dependent upon maternal mRNAs and proteins to transcription of embryonic genes
what occurs during maternal-to-zygotic transition?
transcription of embryonic genes, increased protein synthesis, organelle maturation
what occurs around the 8 cell stage after maternal to zygotic transition? as a morula
compaction
what is embryo compaction?
outer cells become pressed against zona, changing mass from spherical to wedge shaped
outer cells polarised, connect to form tight junctions&desmosomes
forms barrier to diffusion between inner and outer embryo
what occurs after compaction?
blastocyst formation
what is the structure of a blastocyst?
2 distinct cell types (inner cell mass, trophoectoderm)
blastocoel cavity
zona pellucida
what does the inner cell mass contribute to?
pluripotent embryonic cells (form final organism)
what does the trophoectoderm contribute to?
extra-embryonic cells - make extraembryonic structures to support development e.g placenta
what occurs after blastocyst formation?
hatching
what is hatching?
the blastocyst enzymatically digests the zona pellucida and the cell contracts to escape it
(5-6 days post F)
what occurs to the trophoblastic cell lineage during peri implantation events?
days 7-9
fuse to form syncitiotrophoblast which invades and destroys local maternal cells in endometrium
creates interface between embryo & maternal blood supply
cytotrophoblast cells remain individually to provide source of syncitiotrophoblast cells
what does the inner cell mass separate into during peri implantation events?
days 7-9
epiblast - foetal tissues derive from here
hypoblast - forms yolk sac
what occurs at day 12+ to aid pregnancy detection?
syncitiotrophoblast secretes hCG (basis of pregnancy tests)
what is bilaminar embryonic disc formation?
new amniotic cavity forms between epiblast cells
leaves two layer disc of epiblast & hypoblast cells sandwiched between cavities
epiblast cells separated from hypoblast form amnion cells (will form extraembryonic structures)
what occurs after the bilaminar embryonic disc has formed?
gastrulation
what does the endoderm form?
GI tract
liver, pancreas
lung
thyroid
what does the ectoderm form?
CNS and neural crest
skin epithelia
tooth enamel
what does the mesoderm form?
blood muscle heart gonads kidneys adrenal cortex bone, cartilage
when does notochord formation occur in foetal development?
day 13 onwards
what is the notochord?
rod like tube of cartilage-like cells formed along embryo midline under the ectoderm
key organising centre for neurulation and mesoderm development
what is neurulation?
transformation of neural plate into a tube by folding
how is neurulation initiated?
notochord signals direct the neural plate ectoderm to invaginate forming neural groove
neural folds form along cranio-caudal axis
how does the neural tube form?
neural folds formed by invagination of neural plate ectoderm eventually fuse to form a hollow tube
neural tube then overlaid with epidermis (ectoderm)
neural crest cells migrate from folds downwards
what is gastrulation?
formation of body plan via primitive groove invagination
formation of 3 germ layers
(important for forming the body’s axis)
what is the first step of gastrulation?
formation of primitive groove:
primitive streak (thickened structure along epiblast midline) forms from caudal-cranial
expands to create primitive node and primitive pit
continues to form primitive groove
what is the second stage of gastrulation?
invagination:
epiblast cells migrate inward to streak, detach from epiblast and move to interior of embryo
fall into space between epi and hypoblast
cells invade and displace the hypoblast
what is the final stage of gastrulation
formation of germ layers:
definitive endoderm - as cells invaginate, hypoblast cells are displaced forming the layer of endoderm (first cells to invaginate)
mesoderm - cells that invaginated thorough primitive groove are between the new endoderm and old epiblast
ectoderm - old epiblast layer, have not invaginated
what closes first in the neural tube
head then tail
pathologies related to neural tube development
anencephaly - partial skull and brain
spina bifida - open tube at birth usually lower spine
from which end does the primitive streak develop from?
caudal to cranial (tail to head)
what are neural crest cells all derived from
ectoderm
migrate away from ectoderm during neurulation
what is the neural plate?
thickened layer of ectoderm on top
location of neurulation, forms neural groove/folds
key cells derived from neural crest
pigment cells - melanocytes
cranial bones
cardiac - musculoconnective tissue
trunk neurons, sympathetic, parasympathetic and enteric NS
disorders of neural crest migration defects
pigmentation disorders deafness cardiac defects facial defects failure of gut innervation
what two tissues do somites originally form
dermomyotome (subsequent dermatome and myotome)
sclerotome
what is the dermomyotome
somite derived tissue
dermatome - dermis of skin, connective tissues of neck and trunk
myotome - muscles of embryo
what is the sclerotome
vertebrae and rib cartilage from somite derived embryonic tissue
what are somites
structures arising from paired blocks of paraxial mesoderm to the sides of neural tube/notochord
describe the process of formation of the gut tube
primitive gut forms from ventral and lateral folding and pinching off part of the yolk sac
primitive gut then patterned into foregut midgut hindgut
what is the heart derived from
mesoderm
foetal heartbeat detectable around week 6
starts pumping around day 22
what are the lungs derived from
lung bud of endoderm in 4th week of development
splits into two at end of 4th week
what are the gonads derived from
mesoderm
how are gonads differentiated in the mesoderm
presence or absence of SRY gene on Y chromosome
present - sertoli cells form from gonad cells, testis develop
absent - granulosa cells form from gonad cells, ovaries, needs FOXL2 to continue
what is early pregnancy loss
miscarriage before 23 weeks
causes of early pregnancy loss
errors in development
failure of implantation
inability to sustain foetus
what is a miscarriage before 12 weeks
early clinical pregnancy loss
biggest cause of early pregnancy loss? esp older women
aneuploidy
associated with cohesin loss in ageing oocytes (chromatids not held together)
what signalling pathways are indicated in recurrent miscarriages
Lif-deficiency - reduced Lif levels in uterine secretions of subfertile women (leukaemia inhibitory factor)
non selective uterus hypothesis - uterus permits implantation of poor embryo, changes in mucin expression
what is genomic imprinting
epigenetics of gene expression based upon whether the gene was inherited from mother or father
what is a parthenogenic embryo
embryo without fertilisation - all maternal DNA
large embryo, small placenta (so that mother can go on to have other pregnancies)
what is an androgenic embryo?
embryo with only paternal DNA
small embryo, large placenta
what is a hydatidiform mole?
mass of cells that will not grow into a baby due to overwhelming paternal DNA
what is a complete hydatidiform mole
empty egg fertilised by sperm (duplicated) or 2 sperm
what is a partial hydatidiform mole
normal egg fertilised by sperm (duplicated genome) or 2 sperm
what predisposes some females to recurrent molar pregnancies
NLRP-7 mutations
what is a gestational trophoblastic neoplasia
invasive, malignant hydatidiform mole
what is an ectopic pregnancy
implantation of embryo at site other than uterine endometrium
treatment of ectopic pregnancy
chemotherapy
surgery to remove trophoblast
tube removal
risk factors for ectopic pregnancy
age
previous EP
smoking cigarettes or marijuana
STDs
how does smoking cigarettes increase risk of EP?
conitine downregulates expression of PROKR1 which regulates fallopian smooth muscle contractility and also induces pro-apoptosis in fallopian tube epithelium
tobacco smoke inhibits ciliary function
how does cannabis increase risk of ectopic pregnancy (possibly)
CB1 receptor responsible for embryo migration down tube
endocannabinoid signalling higher in all ectopic pregnancies
potential use of exogenous cannabinoids overwhelms/disrupts cannabinoid signalling by either: disrupting receptors, reducing endocannabinoid production or breakdown of endocannabinoids
