pregnancy, parturition and late foetal development Flashcards
what is embryo-foetal growth like in the first trimester?
Embryo-fetal growth during the first trimester is relatively limited
Early embryro nutrition is histiotrophic (derivation of nutrients from the breakdown of surroundnig tissues)
reliant on uterine gland secretions and breakdown of endometrial tissues
how does embryo-foetal growth change in the second trimester?
Switch to haemotrophic support at start of 2nd trimester. (derives nutrients from the maternal blood)
Achieved in humans through a haemochorial-type placenta where maternal blood directly contacts the fetal membranes. (chorion)
happens around the 12th week
it increases the rate of foetal growth
how does the syncitiotrophoblast help contribute to embryo-foetal growth?
in the first trimester
it invades the endometrium, and breaks down the tissue
nutrients can then be derived from the breakdown products
there are also secretions from the uterine glands
and breakdown of capillaries, so syncitiotrophoblast is exposed to maternal blood
what is the amnion?
derivative of the epiblast, but unlike the rest of the epiblast it wont go on to form part of the foetus
instead it is the first of the key foetal membranes
(inner foetal membrane)
it forms the amniotic cavity.
over time this will expand to form the amniotic sac, that surrounds and cushions the foetus
Forms a closed, avascular sac with the developing embryo at one end
Begins to secrete amniotic fluid from 5th week – forms a fluid filled sac that encapsulates and protects the fetus
what is the chorion?
the second of the key foetal membranes
(outer foetal membrane)
outer membrane that surrounds the whole conceptus unit
Formed from yolk sac derivatives and the trophoblast
Highly vascularized
Gives rise to chorionic villi – outgrowths of cytotrophoblast from the chorion that form the basis of the fetal side of the placenta
what is the connecting stalk?
Links developing embryo unit to the chorion
what are trophoblast lacunae?
Large spaces filled with maternal blood formed by breakdown of maternal capillaries and uterine glands
Become intervillous spaces aka maternal blood spaces
what are the foetal membranes?
Fetal membranes: extraembryonic tissues that form a tough but flexible sac encapsulates the fetus and forms the basis of the maternal-fetal interface.
- amnion
- chorion
- allantois
Expansion of the amniotic sac by fluid accumulation forces the amnion into contact with the chorion, which fuse, forming the amniotic sac
Amniotic sac: 2 layers; amnion on the inside, chorion on the outside
what is the allantois?
Outgrowth of the yolk sac
Grows along the connecting stalk from embryo to chorion
Becomes coated in mesoderm and vascularizes to form the umbilical cord.
what are the primary chorionic villi?
Primary chorionic villi:
Cytotrophoblast forms
finger-like projections through syncitiotrophoblast layer Into maternal endometrium
extensions of the chorion
(cytotrophoblast - produces cells that contribute to the syncitiontrophoblast)
will form part of the maternal-foetal interface
what is the purpose of chorionic villi?
Provide substantial surface area for exchange
Finger-like extensions of the chorionic cytotrophoblast, which then undergo branching
wha tare the three stages of chorionic villi development?
Three phases of chorionic villi development:
Primary: outgrowth of the cytotrophoblast and branching of these extensions
Secondary: growth of the fetal mesoderm into the primary villi
Tertiary: growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature.
allows close contact between foetal and maternal blood
what is the microstructure of a terminal villus?
blood vessels from the foetus, coated in trophoblast, project up into the villi
the surrounding space they sit in is the lacunae, so are full of maternal blood
Convoluted knot of vessels and vessel dilation
Slows blood flow enabling exchange between maternal and fetal blood
Whole structure coated with trophoblast
Early pregnancy: 150-200µm diameter, approx. 10µm trophoblast thickness between capillaries and maternal blood.
Late pregnancy: villi thin to 40µm, vessels move within villi to leave only 1-2µm trophoblast separation from maternal blood.
what is the maternal blood supply to the endometrium like?
Uterine artery branches give rise to a network of arcuate arteries. (outside myometrium)
Radial arteries branch from arcuate arteries, and branch further to form basal arteries. (in myometrium towards endometrium)
Basal arteries form spiral arteries during menstrual cycle endometrial thickening. if no implantation, the spiral arteries regress and the endometrium is shed
(in endometrium)
what is spiral artery remodelling?
Spiral arteries provide the maternal blood supply to the endometrium during implantation and foetal development
Extra-villus trophoblast (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endovascular EVT.
Endothelium and smooth muscle is broken down – EVT coats inside of vessels, forming a new endothelial layer
EVT cells replace the maternal endothelium
Conversion: turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow.
this is really important
basically as the villi trophoblast cells invade down into the spiral arteries, it widens them out and makes them lower pressure and higher capacity
what is an overview of the placental structure?
look at diagram in notes
like a big creepy cheshire cat smile
maternal artery on bottom ( with maternal vein wound round it )
lacunae above, these are supplied and filled with blood from the maternal spiral arteries
chorionic villi above, invading the lacunae
foetal artery and vein at the top
and theres a bit kinda like the cupids bow that is the umbilical cord, containing the foetal artery and vein
what nutrients are exchanged across the placenta?
Oxygen: diffusional gradient (high maternal O2 tension, low fetal O2 tension)
Glucose: facilitated diffusion by transporters on maternal side and fetal trophoblast cells.
Water: placenta main site of exchange, though some crosses amnion-chorion. Majority by diffusion, though some local hydrostatic gradients.
Electrolytes: large traffic of sodium and other electrolytes across the placenta – combination of diffusion and active energy-dependent co-transport.
Calcium: actively transported against a concentration gradient by magnesium ATPase calcium pump.
important for development of the skeleton
Amino acids: reduced maternal urea excretion and active transport of amino acids to fetus
what changes occur in the mother due to maternal-foetal oxygen exchange?
Maternal cardiac output increases 30% during first trimester (stroke vol & rate)
Maternal peripheral resistance decreases up to 30%
Maternal blood volume increases to 40% (near term (20-30% erythrocytes, 30-60% plasma)
Pulmonary ventilation increases 40%
what changes occur in the placenta and foetus due to maternal-foetal oxygen exchange?
Placenta consumes 40-60% glucose and O2 supplied
But although fetal O2 tension is low, O2 content and saturation are similar to maternal blood.
Embryonic and fetal hemoglobins: greater affinity for O2 than maternal hemoglobin.
how does the circulatory system mature?
Placenta acts as site of gas exchange for fetus
Ventricles act in parallel rather than series
vascular shunts bypass pulmonary & hepatic circulation -> close at birth
Organ maturation is co-ordinated by fetal cortico-steroids.
how does the respiratory system mature?
Primitive air sacs form in lungs around 20 weeks, vascularization from 28 weeks
Surfactant production begins around week 20, upregulated towards term
Fetus spends 1-4h/day making rapid respiratory movements during REM sleep
Organ maturation is co-ordinated by fetal cortico-steroids.
how does the gastro intestinal system mature?
Endocrine pancreas functional from start of 2T, insulin from mid-2T
Liver glycogen progressively deposited – accelerates towards term
Large amounts of amniotic fluid swallowed –debris and bile acids form meconium (the first stool
Organ maturation is co-ordinated by fetal cortico-steroids.
how does the nervous system mature?
Fetal movements begin late 1T, detectable by mother from ~14 weeks
Stress responses from 18 weeks, thalamus-cortex connections form by 24 weeks
Fetus does not show conscious wakefulness – mostly in slow-wave or REM sleep
Organ maturation is co-ordinated by fetal cortico-steroids.
what is labour?
Safe expulsion of the fetus at the correct time
Expulsion of the placenta and fetal membranes
Resolution/healing to permit future reproductive events
Labour has the characteristics of a pro-inflammatory reaction:
Immune cell infiltration
Inflammatory cytokine and prostaglandin secretion
what are the phases of pregnancy in terms of parturition?
1: quiescent phase
prelude to parturition
contractile -unresponsiveness, cervical softening
2: activation
preparation for labour -
uterine preparedness for labour, cervical ripening
3: stimulation
process of labour -
uterine contraction, cervical dilation, foetal and placenta expulsion
(three stages of labour)
4: involution
parturient recovery -
uterine incolution, cervical repair, breast feeding
what are the three stages of labour?
First Stage:
Contractions start,
Cervix dilation
Latent Phase-
Slow dilation of the cervix to 2-3cm
Active Phase-
Rapid dilation of the cervix to 10cm
Second stage:
Delivery of the fetus
Commences at full dilation of the cervix (10cm)
Maximal myometrial contractions
Third stage:
Delivery of the placenta
Explusion of placenta and fetal membranes
Post-partum repair
what is remodelling of the cervix?
Cervix has a critical role in retaining the fetus in the uterus.
High connective tissue content:
Provides rigidity
Stretch resistant
Bundles of collagen fibres embedded in a proteo-glycan matrix
Changes to collagen bundle structure underlie softening, but mechanism unclear.
what are the stages of cervix remodelling?
- Softening – begins in first trimester
Measurable changes in compliance but retains cervical competence - Ripening – weeks and days before birth
Monocyte infiltration and IL-6 and IL-8 secretion
Hylaluron deposition - Dilation – increased elasticity
Increased hyaluronidase expression -> HA breakdown
MMPs decrease collagen content - Post-partum repair
Recovery of tissue integrity and competency
what is the role of corticotrophin releasing hormone in the initiation of labour?
Current thinking: fetus determines timing of parturition through changes in fetal HPA axis
CRH levels rise exponentially towards the end of pregnancy
Decline in CRH binding protein levels, so CRH bioavailability increases
what are the functions pf Corticotrophin releasing hormone in labour?
promotes fetal ACTH and cortisol release
Increasing cortisol drives placental production of CRH -> Positive feedback!
stimulates DHEAS production by the fetal adrenal cortex -> substrate for estrogen production
what are oestrogen and progesterone like during labour?
High progesterone through pregnancy maintains uterine relaxation
Serum estrogen:progesterone ratio may shift in favour of estrogen – this is unclear
levels of oestrogen and progesterone increase during pregnancy
As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) isoforms expressed in the uterus -> functional prog. withdrawal
Rise in Estrogen Receptor Alpha expression
Uterus becomes ‘blinded’ to progesterone action and sensitized to estrogen action
Control of these changes unclear but likely leads to local changes in E:P ratio in uterine tissues.
what happens to oxytocin in labour?
Nonapeptide (9aa) hormone synthesized mainly in the utero-placental tissues and pituitary:
Uterine oxytocin production increases sharply at onset of labour
Expression increase is driven by increase in estrogen levels.
Release promoted by stretch receptors -> Ferguson reflex
Signals through G-coupled oxytocin receptor (OTR / OXTR)
Pre-labour: progesterone inhibits OXTR expression -> uterus relaxed
Rise in estrogen promotes
large increase in uterine OXTR expression
what is the role of oxytocin?
Increases connectivity of myocytes in myometrium (syncytium)
Destabilise membrane potentials to lower threshold for contraction
Enhances liberation of intracellular Ca2+ ion stores
what is the role of prostaglandins in labour?
Primary PGs synthesized during labour are PGE2, PGF2alpha and PGI2.
Rising estrogen levels drive prostaglandin action in the uterus in two ways:
- Rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
- Estrogen stimulation of oxytocin receptor expression promotes PG release.
PGE2 – cervix re-modelling
Promotes leukocyte infiltration into the cervix, IL-8 release and collagen bundle re-modelling
PGF2alpha – myometrial contractions
Destabilises membrane potentials and promotes connectivity of myocytes (with Oxytocin)
PGI2 - myometrium
Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segnment.
important for inbetween contractions
Other factors: peptide hormone relaxin and nitric oxide (NO) implicated in cervix re-modelling
what is an integrated hypothesis for the regulation of labour?
big diagram, look at notes
involves CRH from foetus pituitary, then positive feedback from CRH from placenta
DHEAS increase
oestrogen increase
oxytocin increase
prostaglandins
(progesterone inhibits all of these not during labour)
what are myometrial contractions?
Myometrial muscle cells form a syncytium (extensive gap junctions)
Contractions start from the fundus, spread down upper segment
Muscle contractions are brachystatic –fibres do not return to full length on relaxation
This causes lower segment and cervix to be pulled up forming birth canal
what is foetal expulsion?
Head engages with pelvic space 34-38wks
Pressure on fetus causes chin to press against chest (flexion)
Fetus rotates (belly to mother’s spine) Head expelled first after cervix dilates
Shoulders delivered sequentially (upper first) followed by torso.
what is placental expulsion and repair?
final phase
Rapid shrinkage of the uterus after fetal delivery causes area of contact of placenta with endometrium to shrink
Uterine shrinkage also causes folding of fetal membranes – peel off the endometrium
Clamping of the umbilical cord after birth stops fetal blood flow to placenta -> villi collapse
Hematoma formation between decidua and placenta
Contractions expel placenta and fetal tissues
Uterus remains contracted after delivery to facilitate uterine vessel thrombosis.
Uterine involution and cervix repair restore non-pregnant state:
Shielding uterus from commensural bacteria
Restore endometrial cyclicity in response to hormones
