just everything Flashcards
oct4 k/o in mice and humans
mice: blastocysts still form, but ICM all differentiate to trophectoderm
humans: if gene encoding is deleted (POV5F1?), then iCM + blastocyst formation = compromised
NANOG is a key factor in what
epiblast specification
CDX oppresses?
OCT4 in the TE
Cdx2 k/o
oct4 isn’t downregulated, so the blastocyst forms but then collapses and arrests
human embryos treated with FGF/ERK inhibitors
do not form epiblast - only ICM
IGF1 is what
a survival factor, it stimulates protein synthesis
FGF4 maintains what
trophoblast SC population
fertility problems affect how many people uk world
1/6 uk
10% (3.5mil) world
female factors to infertility
failure to ovulate
blocked/filled fallopian tubes
endometriosism
male factors to infertility
low # sperm
poor sperm motility
suboptimal # of normal sperm
ART diagnostics female
of oocytes
morphology of oocytes (immature, mature MII, degenerated)
ability of oocytes to be fertilized
ART diagnostics male
sperm # and quality
ability to fertilize egg (ability to penetrate zona pellucida)
ART diagnostics embryo quality
cleavage rate (pattern and timing)
blastocyst foration
PGD-aneuploidy, chromosomal abnormalities
steps of natural fertilization
- oocyte at metaphase II released
- fertilized by single sperm - zygote
- pre-implantation development in fallopian tube
- implantation of blastocyst in uterus - pregnancy
(IVF = 1-3 outside body)
early vs late embryo transfer pros and cons
early:
- no chance to assess which embryo are likely to be viable /healthy
- being put back in uterus as cleavage stage embryo = wrong environment
- avoids potentially damaging culture conditions
day 5 transfer (later):
- allows morphological assessment of choice of best blastocyst
- culture env. may have adverse conditions / consequences
- if embryos didn’t survive in vitro, no emryos can be transferred
decidualization
stromal fibroblasts transform to become enlarged decidual cells - in respnse to progesterone (and to inflammatory signals when implantation = underway)
decidual cells secrete regulatory signals to control immune microenvironment and to provide a permissible environment for gestation
only progesterone is required to signal for decidualization in humans
in conception, the implanting embryo produces what to maintain progesterone levels
hcg
only ____ produce HCG
trophoblast - must develop rapidly to produce enough HCG to signal
hcg does what
rescues corpus luteum (luteotrophic) - it can then continue to produce progesterone
histioptrophic nutrition
stroma contributes to producing some nutrients for embryo
nourishes embryo up to 11 weeks via trophoblast, coelemic cavity and yolk sac
the steps / stages of placental villous development
primary villous stage (10dpf)
- cytotrophoblast protrusion
secondary villous stage (12dpf)
- extra embryonic mesoderm incursion
- branching - increases surface area
tertiary villous stage (20dpf)
- vascularization
core placental functions
- protective barrier
- nutrient + gas exchange
- hormone secretion + production
- syncytiotrophoblast = placenta’s endocrine tissue
mechs of exchange placental
transcellular facilitated diffusion
- facilitated by transmembrane transport proteins
trasnport along [] gradient - maternal plasma glucose [] = higher than fetal
transcellular active diffusion
- mediated by transporter proteins
- requires energy
transcytosis
- receptor mediated - e.g. immunoglobin
- receptor independent - small molecular proteins
villous vs extravillous trophoblast functions
villous = transport, immunological barrier, secretion / endocrine
extravillous: anchorage, plugging of arteriolar openings, migration and spiral artery remodelling
changes in vasculature in pregnancy
increase in blood by 35-50% - this is accommodated by:
- increase in CO, stroke volume, HR
- decrease in peripheral resistance
chorionic villi does what
imports oxygen from maternal blood
regress in the region of the chorioamnion
imports oxygen from maternal blood
hemochorial placenta requires ___ to flow through intervillous space - it also does what?
maternal blood
supplies lipids to fetus in second and third trimester
at term, the placenta has
a ______ syncytiotrophoblast layer
_____ membranes
________ villus diameter
thinner
vasculo-syncytial
decreased
syncytiotrophoblast
- layer of ________ cells
- terminally ________
- develops by _______ and fusion of ______
multinuclear non-proliferative
differentiated
proliferation / cytotrophoblast
barker hypothesis
correlation between low birth weight and incidence of death from CVD
H19 is a negative regulator of what
IGF II
IGF II function
promotes placental development and transporter activity
liquorice fun fact
has glycyrrhiza = 11betaHSD2 inhibitor
consumption is high in scandinavia
it can result in earlier labour, cognitive behavioural problems in children (bc high cortisol exposure has effects on brain development)
11betaHSD2 inactviates cortisol by converting it to cortisone
FGR does what (4)
reduced cytotrophoblast proliferation
increases apoptosis
increases synctyal knots
placental amino acid transporter activity
in humans, GC treatment does what
impairs angiogenesis
reduces branching
reduces vegfa nd other angiogenic factors
reduces IGF-1 expression