Age + Dev - Placentation + Pregnancy Flashcards
How does the embryo gain nutrition and grow in the first trimester?
Histiotrophic
What is histiotrophic support?
Gaining nutrients from the breakdown of endometrial tissues and uterine gland secretions for growth and development
Give an example of histiotrophic growth in early foetal development.
Synctiotrophoblasts invading maternal endometrium - this breakdown of local tissues + maternal capillaries fuels some of the embryo’s development
What type of support does the embryo switch to at the start of the 2nd trimester?
Haemotrophic support
What haemotrophic support?
Deriving nutrient directly from the maternal blood
Why does embryo support switch from histiotrophic to haemotrophic?
Needs to switch to maintain the increasing rate of growth of the embryo from 1st trimester to 2nd
How is haemotrophic support achieved?
Achieved through a haemochorial-type placenta where maternal blood directly contacts the fatal membranes
What are trophoblastic lacunae?
→ Large spaces filled with maternal blood formed by breakdown of maternal capillaries + uterine glands
→ become intervillous spaces AKA maternal blood spaces
What are fetal membranes?
Extra embryonic tissues that form a tough but flexible sac encapsulates the foetus and forms the basis of the maternal-fetal interface
What are the 4 different fetal membranes?
→ Innermost = Amnion
→ Outermost = Chorion
→ Allantois
→ Yolk Sac or Umbilical Vesicle
What is the amnion?
→ Innermost fetal membrane
→ Arises from the Epiblast but doesn’t contribute to the fetal tissues
→ Forms a closed avascular sac with the developing embryo at one end
→ Begins to secret amniotic fluid around the 5th week to fill the amniotic sac
What is the chorion?
→ Outer fetal membrane
→ Firmed from yolk sac derivatives and the trophoblast
→ Highly vascularised
→ Gives rise to the chorionic Villi
What is the connecting stalk?
Links developing embryo unit to the chorion
What is the allantois?
→ Outgrowth of the yolk sac
→ Grows along the connecting stalk from embryo to chorion
→ Becomes coated in mesoderm + vascularises to form the umbilical chord
What is the amniotic sac?
→ Inner membrane = amnion
→ Outer membrane = chorion
→ Fluid filled sac formed by the production of amniotic fluid
→ Encapsulates and protects the foetus
→ Forces amnion into contact with the chorion
What are chorionic villi?
Cytotrophoblast forms finger-like projections through syncitiotrophoblast layer into maternal endometrium
What is the main function of chorionic villi?
Provide substantial surface area for exchange
What are the 3 phases of chorionic villi development?
→ Primary
→ Secondary
→ Tertiary
What is the primary phase of chorionic growth?
Outgrowth of the cytotrophoblast and branching of its extensions
What is the secondary phase of chorionic villi growth?
Growth of the fetal mesoderm into the primary villi
What is the tertiary phase of chorionic villi growth?
Growth of the umbilical artery + vein into the villus mesoderm, providing vascular use
What is the microstructure of the terminal chorionic villus?
→ Convoluted knots of vessels with vessel dilation
→ Slows blood flow enabling exchange between maternal and fetal blood
→ Whole structure coated with trophoblast
What are the difference in terminal villus microstructure in early pregnancy and late pregnancy?
Villi become much thinner, vessels move within the villi to leave less trophoblast separation between maternal blood and capillaries
What arteries does the blood supply to the endometrium consist of?
→ Uterine artery give rise to network of Arcuate arteries in the myometrium
→ Arcuate arteries branch into Radial arteries
→ Radial arteries further branch into Basal arteries in the endometrium
→ Basal arteries form Spiral arteries during the menstrual cycle endometrial thickening
How do spiral arteries remodel to become the maternal blood supply during pregnancy?
→ Extra-villus trophoblasts (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endo vascular EVT
→ Endothelium and smooth muscle is broken down - EVT coats the inside of vessels
→ Turns spiral artery into low pressure, high capacity conduit for maternal blood flow
What is the process of spiral artery remodelling in pregnancy called?
Conversion
How is oxygen exchanged across the placenta?
diffusional gradient (high maternal O2 tension, low O2 fatal tension
How is glucose exchanged across the placenta?
facilitated diffusion by transporters on maternal side `+ fetal trophoblast
How is water exchanged across the placenta?
→ placenta is main site of exchange, though some H2O crosses at the amnion-chorion border
→ majority is by diffusion, with some local hydrostatic gradients
How are electrolytes exchanged across the placenta?
large traffic of sodium + other electrolytes across the placenta - combo of diffusion + active energy-dependent co-transport
How is calcium exchanged across the placenta?
actively transported against a conc. gradient by magnesium ATPase calcium pump
How are amino acids exchanged across the placenta?
reduced maternal urea excretion + active transport of AAs to foetus
What are the maternal changes when the maternal-fetal oxygen exchange occurs`?
→ maternal cardiac output increase 30`% during first trimester (stroke volume & rate)
→ maternal peripheral resistance decreases up to 30%
→ maternal blood volume increases to 40%
→ pulmonary ventilation increases 40%
What are the fetal changes when the maternal-fetal oxygen exchange occurs`?
→ placenta consumes 40-60% glucose and oxygen supplied
→ fetal O2 tension is low
→ O2 content + saturation are similar to maternal blood
→ embryonic + fetal haemoglobins have a greater affinity for O2 than maternal haemoglobin’s
Describe how the circulatory system matures from 1st trimester to 2nd trimester.
→ 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
Describe how the respiratory system matures from 1st trimester to 2nd trimester.
→ Primitive air sacs form in lungs around 20 weeks, vascularization from 28 weeks
→ Surfactant production begins around week 20, up-regulated towards term 2
→ Fetus spends 1-4h/day making rapid respiratory movements during
Describe how the gastrointestinal system mature from 1st trimester to 2nd trimester.
→ 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
Describe how the nervous system mature from 1st trimester to 2nd trimester.
→ 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
How is feral organ maturation co-ordinated?
fetal corticosteroids
What is the purpose of labour?
→ Safe expulsion of the fetus at the correct time
→ Expulsion of the placenta and fetal membranes
→ Resolution/healing to permit future reproductive events
What are the 4 phases of pregnancy from conception to fertility restoration?
→ phase 1 : QUIESCENCE : prelude to parturition
→ phase 2 : ACTIVATION : preparation for labour
→ phase 3 : STIMULATION : processes of labour
→ phase 4 : INVOLUTION : parturient recovery
What are the characteristics of Phase 1?
→ between conception and initiation of parturition
→ contractile, unresponsiveness
→ cervical softening
What are the characteristics of phase 2?
→ between initiation of parturition and onset of labour
→ uterine preparedness for labour
→ cervical ripening
What are the characteristics of phase 3?
→ between onset of labour and delivery of conceptus → uterine contraction → cervical dilation → fetal and placenta expulsion → involves 3 stages of labour
What are the characteristics of phase 4?
→ between delivery of conceptus and fertility restoration
→ uterine involution
→ cervical repair
→ breast feeding
What type of reaction does labour share the characteristics of? Why?
pro-inflammatory reaction
→ immune cell infiltration
→ inflammatory cytokine + prostaglandin secretion
What are the 3 stages of labour?
1 = contractions start + cervix dilation 2 = delivery of fetus 3 = delivery of the placenta
What can the first stage be divided into?
→ latent phase
→ active phase
What is involved in the latent part of the first stage?
slow dilation of the cervix to 2-3cm
What is involved in the active stage of the first stage?
rapid dilation of the cervix to 10cm
What is involved in the second stage of labour?
→ commences at full dilation of the cervix (10cm)
→ maximal myometrial contractions
What is involved in the third stage?
→ expulsion of placenta + fatal membranes
→ post-partum repair
How long is the first delivery typically?
8-18 hrs
How long are subsequent deliveries typically?
5-12 hrs
What is the role of the cervix?
retains fetus in uterus
What features does the cervix have in order to be able to complete its function?
→ 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 4 phases of cervix remodelling?
→ softening
→ ripening
→ dilation
→ post-partum repair
What is involved in the softening of the cervix?
→ begins in first trimester
→ measurable changes in compliance but retains cervical competence
What is involved in the dilation of the cervix?
→ Increased hyaluronidase expression -> HA breakdown
→ MMPs decrease collagen content
What is involved in the ripening of the cervix?
→ increased elasticity
çmonocyte infiltration and IL-6 and IL-8 secretion hylaluron deposition
What is involved in post-partum repair?
recovery of tissue integrity and competency
How does a fetus determine timing of parturition?
→ through changes in fetal HPA axis
→ corticosteroids-releasing hormone rise exponentially towards the end of pregnancy
→ decline in CRH binding protein levels so CRH bioavailability increases
What are the functions of CRH 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 is the progesterone level throughout pregnancy? Explain.
high progesterone = uterine relaxation
How does the oestrogen to progesterone ratio change towards the end of the pregnancy?
→ serum E:P ratio shifts in favour of E
→ 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 type of hormone is oxytocin?
nonapeptide (9aa) hormone
Where is oxytocin produced?
→ utero-placental tissues
→ pituitary
When does uterine oxytocin production increase?
sharply at the onset of labour
What is oxytocin expression driven by?
oestrogen levels
What is oxytocin release promoted by?
stretch receptors (Ferguson reflex)
What is the Ferguson Reflex?
neuroendocrine reflex in which the fetal distension of the cervix stimulates a series of neuroendocrine responses, leading to oxytocin production
What receptors respond to oxytocin in the uterus?
G-coupled oxytocin receptor (OTR / OXTR)
What inhibits the expression of OXTRs / OTRs pre-labour?
progesterone (keeps the uterus relaxed)
What increases OTR / OXTR expression?
rise in oestrogen
What are the functions of oxytocin during labour?
→ increases connectivity of myocytes in myometrium (syncytium)
→ destabilise membrane potentials to lower threshold for contraction
→ enhances liberation of intracellular Ca2+ ion stores
What are the key effectors of labour?
prostaglandins
What are the 3 primary prostaglandins synthesised during labour?
→ PGE2
→ PGF2-alpha
→ PGI2
What drives prostaglandin action in uterus?
rising oestrogen levels
In what 2 ways does oestrogen drive prostaglandin action in the uterus?
→ rising oestrogen activates phospholipase A2 enzyme = generating more arachidonic acid for PG synthesis
→ oestrogen stimulation of oxytocin receptor expression promotes prostaglandin release
What are the functions of PGE2?
→ cervi xremodelling
→ promotes leukocyte infiltration into the cervix, IL-8 release + collagen bundle re-modelling
What are the functions of PGF2-alpha?
→ myometrial contractions
→ destabilises membrane potentials + promotes connectivity of myocytes (w/ Oxytocin)
What are the functions of PGI2?
→ promotes myometrium smooth muscle relaxation
→ relaxation of lower uterine segments
What are some other factors involved in cervix remodelling?
→ peptide hormone RELAXIN
→ NO - nitric oxide
What do myometrial muscle cells form?
synctium (multi-nucleate cell formed from unicellular cells) with extensive gap junctions
Where do contractions of the myometrium start? Where do they spread?
→ fundus
→ spread down upper segment
How are the myometrial muscle contractions described?
brachystatic
→ fibres don’t return to full length on relaxation
What do the brachystatic contractions of the myometrium form?
lower segment + cervix get pulled up = forms birth canal
What happens to the uterus after fetal delivery?
rapid shrinkage of uterus
What does uterus shrinkage cause?
→ area of contact of placenta with endometrium shrinks
→ folding of fetal membranes (they peel off the endometrium)
What does the clamping of the umbilical cord lead to?
→ stops fetal blood flow to placenta
→ causes villi colapse
What forms between the decidua and placenta after fetal delivery?
hematoma
How are the placenta + fetal tissues expelled from the uterus after fetal delivery?
→ uterus rapidly shrinks after delivery
→ area of contact between placenta + endometrium shrinks
→ fetal membranes begin to fold + peel off the endometrium
→ hematoma forms between placenta + decidua
→ contractions expel placenta + fetal tissues
Does the uterus contract or relax after delivery? Why?
→ contracted
→ to facilitate uterine vessel thrombosis
How is the non-pregnant state of the uterus restored?
→ uterine involution + cervix repair
→ shielding uterus from commensurate bacteria
→ restore endometrial cyclicity in response to hormones
