(dev&age) pregnancy, parturition and late fetal development Flashcards
what is parturition?
childbirth
what is embryo-fetal growth like in the first trimester?
very limited and slow
what is early embryo nutrition in the first trimester described as?
histiotrophic embryo nutrition
what is late embryo nutrition in the second trimester onwards described as?
haemotrophic embryo nutrition
what is histiotrophic nutrition?
provision of nutrients for the embryo via the uterine gland secretion and the breakdown of surrounding endometrial tissue
what two things is histiotrophic embryo nutrition reliant on?
uterine gland secretions (of uterine milk)
breakdown of surrounding endometrial tissue
what do the uterine glands secrete and why is this important?
uterine milk
what is uterine milk?
nutritive secretion from the uterine glands that nourishes the embryo
how do syncitiotrophoblast cell contribute to histiotrophic nutrition?
invade and degrade the maternal endometrial cells
the products of the endometrial tissue breakdown AND the nutrients from the maternal capillaries = give nutrients to the embryo
how does the rate of foetal growth change from the first trimester onwards?
increases rapidly in the second and third trimester
how does embryo nutrition change from the first to the second trimester?
switches from histiotrophic to haemotrophic nutrition
why does the type of embryo nutrition change from the first to the second trimester?
the rate of foetal growth increases significantly and histiotrophic nutrition is not enough to keep up with this increased growth rate
what is haemotrophic nutrition?
the provision of nutrients for the embryo via the exchange of nutrients across the maternal and fetal circulations
when does haemotrophic nutrition begin?
at the start of the second trimester
what type of placenta is present in humans?
haemochorial-type placenta
why is the haemochorial-type placenta important for?
essential for enabling haemotrophic nutrition from the start of the second trimester
enables the maternal blood to be directly in contact w the fetal membranes
what is a haemochorial-type placenta?
a placenta type wherein the blood supply (maternal) is directly in contact with the fetal membranes
what causes the switch of nutrition from histiotrophic to haemotrophic and what does this cause?
the activation of the hameochorial-type placenta at around week 12 of gestation (i.e. start of the second trimester)
what is the chorion?
the outermost layer of the embryo
develops from the outer fold of yolk sac
differentiate between histiotrophic and haemotrophic development
histiotrophic nutrition comes from the uterine gland secretions and the breakdown of the surrounding endometrial cells
whereas haemotrophic nutrition is the provision of nutrients from the maternal blood to the fetal membranes via direct contact
what type of growth occurs in the early implantation stage?
histiotrophic growth
what are the main sources of nutrients for the embryo in the early implantation stage?
uterine secretions from the glands (of uterine milk)
nutrients from the maternal capillaries + the breakdown of endometrial tissues
what is the amnion?
the inner fetal membrane (derived from the epiblast) that forms a fluid-filled cavity (amniotic sac) enclosing the embryo
what is the amnion derived from?
epiblast cells
what does the amnion give rise to?
forms a fluid-filled cavity called the amniotic sac that encloses the embryo
what is the amniotic sac?
fluid-filled cavity that encloses the embryo
what are the two fetal membranes?
chorion (outer)
amnion (inner)
how are the fetal membranes arranged?
chorion on the outside and amnion on the inside, containing amniotic fluid
how does the amnion form the amniotic sac?
forms due to the amnion cells secreting fluid which accumulates, causing an expansion of the amniotic cavity
which cells give rise to the yolk sac?
hypoblast cells
what is the function of the connecting stalk?
grows from the embryo to connect the developing embryo unit to the chorion
what is the connecting stalk?
precursor to the umbilical cord
extraembryonic tissue that connects the embryo unit to the chorion
what are the trophoblastic lacunae?
large spaces filled with maternal blood formed from the breakdown of maternal capillaries and uterine glands
= become intervillous spaces
how do trophoblastic lacunae form?
when syncytiotrophoblast cells invade and degrade the maternal capillaries and the endometrial tissue (i.e. uterine glands) etc break down = large spaces are left
fuse together to create continuous canals along which maternal blood flows
what do trophoblastic lacunae become?
intervillous spaces (i.e. maternal blood spaces)
what are intervillous spaces?
maternal blood spaces
i.e. large spaced filled w maternal blood that are formed from uterine gland and maternal capillary breakdown
name the two main fetal membranes
amnion, chorion
what are fetal membranes?
extraembryonic tissue that forms a tough, but flexible sac that encapsulates the fetus and forms the basis of the maternal-fetal interface
what kind of tissue are fetal membranes?
extraembryonic tissue
what is the function of the fetal membranes?
for a tough but flexible sac that encapsulates the fetus and forms the basis of the maternal-fetal intereface
how does the amnion come into contact with the chorion?
accumulation of amniotic fluid in the amniotic cavity (due to secretion from the amnion cells) pushes the amnion out to the chorion
they eventually fuse together (at week 14-16) to form amniotic sac
how do the amnion and chorion interact?
usually fuse together between week 14 and week 16 of gestation (closing the chorioamniotic separation)
what is the space between the amnion and the chorion called?
anechoic space
when do the amnion and chorion fuse?
approx week 14-16 o gestation
why is the fusion of the amnion and chorion important?
leads to the formation of the amniotic sac
what is the amnion?
inner fetal membrane
what is the chorion?
outer fetal membrane
name all the fetal membranes
chorion
amnion
allantois
what is the allantois?
outgrowths of the yolk sac
which cells does the amnion come from?
epiblast cells (but does not contribute to the fetal tissue)
what does the amnion give rise to?
forms a closed, avascular amniotic sac
what do the amnion cells secrete?
at week 5, they being to secrete amniotic fluid
leads to the formation of the amniotic sac that encapsulates and protects the fetus
when do the amnion cells begin to secrete amniotic fluid?
approx week 5 of gestation
why is the amniotic sac important?
essential for encapsulating and protecting the fetus
what gives rise to the chorion?
formed from yolk sac derivatives and the trophoblast
differentiate between the amnion and chorion in terms of vascularity
the amnion is avascular whereas the chorion is highly vascularised
what is the vascularity of the chorion like?
chorion is highly vascularised
what does the chorion give rise to?
gives rise to chorionic villi (outgrowths of cytotrophoblast) from the chorion that form the basis of the fetal side of the placenta
what are the chorionic villi?
outgrowths of cytotrophoblast from the chorion
what is the purpose of the chorionic villi?
(form from the cytotrophoblast from the chorion)
form the basis of the fetal side of the placenta
what forms the basis of the fetal side of the placenta?
the chorionic villi (form from the cytotrophoblast)
where does the allantois grow?
grows along the connecting stalk from the embryo to the chorion
which structure is the allantois linked to?
connecting stalk (grows along it)
how does the allantois develop with time?
becomes coated with mesoderm and become vascularised to form the umbilical cord
why is the vascularisation of the allantois important?
leads to the formation of the umbilical cord
which structure does the allantois give rise to?
umbilical cord
describe how the amniotic sac is formed
the amnion cells being to secrete amniotic fluid into the amniotic cavity that accumulates over time and causes an expansion of the amnionic membrane so it is forced into contact with the chorionic membrane with which it fuses to form the amniotic sac
describe the structure of the amniotic sac
two layers: inner amnion (contains amniotic fluid and fetus) and outer chorion (contains amnion and part of the placenta)
what are the two functions of the allantois?
contributes to the embryonic bladder
becomes vascularised to form the umbilical cord
what is the umbilical cord?
a narrow tube that connects the baby to the placenta for the provision of nutrients and removal of waste products
why is the umbilical cord important?
enables the provision of nutrients for the developing fetus and the removal of toxic waste substances
(i.e. circulatory link to the fetal side of the placenta)
what does the amnion encapsulate?
the amniotic fluid and the developing fetus
what does the chorion encapsulate?
the amnion and part of the placenta
how do the primary chorionic villi form?
cytotrophoblast proliferates and form finger-like projection that extend past the syncitiotrophoblast into the maternal endometrium
into which layer do the chorionic villi protrude?
extend past the syncitiotrophoblast into the maternal endometrium
what are the main function of the cytotrophoblast?
main = act as a dividing cell population that proliferates to constantly replenish and contribute to the syncitiotrophoblast cell population
where do the chorionic villi develop?
outside of the chorion (past the syncitiotrophoblast into the maternal endometrium)
what do the chorionic villi contribute to?
the maternal-fetal interface
how are the chorionic villi adapted to their function?
they are highly branched and so provide a larger surface area for the exchange of gases and nutrients
what are chorionic villi?
finger-like projection stemming from the cytotrophoblast, that then undergo branching to contribute to the fetal side of the placenta
name the three phases of chorionic villi development
primary, secondary and tertiary chorionic villi development
describe the three phases of chorionic villi development
primary = outgrowth of the cytotrophoblast and branching of these extensions to form primary villi
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
what occurs in primary chorionic villi development?
outgrowth of the cytotrophoblast and branching of these extensions to form primary villi
what occurs in secondary chorionic villi development?
growth of the fetal mesoderm into the primary villi
what occurs in tertiary chorionic villi development?
growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature
what is chorionic villi development?
the process by which fetal primary chorionic villi form and become invaded by mesoderm and blood vessels to ensure maximal contact between maternal and fetal blood for efficient exchange
why is chorionic villi development important?
the invasion of the primary villi by the mesoderm and blood vessels is essential to provide
1) close contact
2) a large SA
= between maternal and fetal blood for efficient exchange of gases and nutrients
which blood vessels grow into the villus mesoderm in tertiary chorionic villi development?
uterine and umbilical arteries
what structure grows into the primary villi in secondary chorionic villi development?
fetal mesoderm
describe the microstructure of the terminal villus
villus is arranged in a convoluted knot of vessels
vessels are dilated
whole structure is covered in trophoblast
how does the structure of the terminal villus ensure it is adapted to its function?
convoluted knot and the dilated vessels
= ensure the flow of blood is slowed
= so maximal efficiency in the exchange of nutrients and gases between maternal and foetal blood
what is the terminal villus coated in?
trophoblast
what two structural features of the terminal villus maximise efficient exchange between the maternal and foetal blood?
convoluted knot structure
vessel dilation
why is it important that the terminal villus has a convoluted knot?
ensures the flow of blood is slowed to allow maximal efficiency of gas and nutrient exchange between the maternal and foetal blood
why is it important that vessel dilation occurs at the terminal villus?
ensures the flow of blood is slowed to allow maximal efficiency of gas and nutrient exchange between the maternal and foetal blood
describe the structure of the terminal villus during early pregnancy
150-200µm in diameter
10µm trophoblast thickness between capillaries and maternal blood
(i.e. maternal blood spaces surround the capillaries)
describe the structure of the terminal villus during late pregnancy
40µm in diameter
1-2µm trophoblast thickness between capillaries and maternal blood
(i.e. maternal blood spaces surround the capillaries)
how does the terminal villus change structurally as pregnancy progresses?
there is a decrease in the diameter of terminal villi
thinning of the trophoblast layer coating the terminal villi
explain why the structural changes in the terminal villi are important as pregnancy progresses
trophoblast thinning and diameter decrease
= essential as the blood vessels become close to the maternal blood supply so the diffusion distance for gases and nutrients is significantly reduced
= can keep up with the increased rate of fetal development and increased demand
how does trophoblast thickness change at the terminal villus as pregnancy progresses?
trophoblast layer thins from 10µm to approx 1-2µm
how does vessel diameter change at the terminal villus as pregnancy progresses?
vessel diameter falls from 150-200µm to approx 40µm
what is the impact of trophoblast layer thinning AND diameter decrease in terminal villi as pregnancy progresses?
the blood vessels will become closer to the maternal blood supply = reduced diffusion distance
describe the maternal blood supply to the endometrium
the ovarian and uterine arteries anastomose to give rise to the arcuate artery
arcuate artery branches to give rise to the radial arteries
radial arteries branch to give rise to the basal arteries
basal arteries spiralise to form the spiral arteries
list the arteries and their branches supplying the endometrium
ovarian + uterine artery
(myometrium)
arcuate artery
radial artery
basal artery
(endometrium)
spiral artery
which two arteries anastomose to give rise to the arcuate artery?
ovarian and uterine arteries
what does the arcuate artery give rise to?
radial artery
what do the radial arteries give rise to?
basal artery
what do the basal arteries form?
spiralise to form spiral artery
what are the three uterine layers?
perimetrium
myometrium
endometrium
which arteries supply the myometrium?
arcuate, radial, and basal arteries
which arteries supply the endometrium?
spiral arteries
how does the endometrial blood supply develop through the menstrual cycle?
menstrual cycle progresses and endometrial thickening occurs
terminal basal arteries will grow and spiralise to form the spiral arteries form and grow out further during endometrial development
how does successful implantation affect the endometrial blood supply?
if implantation is successful, the spiral arteries remain intact and stabilise
= provide maternal blood supply to the foetus
how does failed implantation affect the endometrial blood supply?
if implantation is unsuccessful
= regression of the spiral arteries
= endometrium is lost due to lack of blood supply (i.e. the monthly menstrual period)
what causes the regression of the spiral arteries?
unsuccessful implantation of an embryo
when do the basal arteries form the spiral arteries?
during endometrial development
terminal basal arteries spiralise to form spiral arteries
what does failed implantation result in and how?
a menstrual period
regression of the spiral arteries causes loss of the thickened endometrial lining
why are the spiral arteries important?
responsible for the endometrial blood supply
describe how the tertiary chorionic villi are arranged in relation to the endometrium
tertiary chorionic villi are arranged above the endometrium
with their trophoblast layer in close contact with the endometrium
what is EVT?
a form of differentiated trophoblast cells of the placenta
extra-villus trophoblast (EVT) are cells that are found on the surface of the tertiary chorionic villi that will invade down into the maternal spiral arteries
what action is carried out by EVT?
invade down into the maternal spiral arteries to form endovascular EVT
(stimulate by IGF-II and IGFBP-I)
once the EVT invade the maternal spiral arteries, what forms?
endovascular EVT
what is endovascular EVT?
a form of differentiated trophoblast cells of the placenta
responsible for the remodelling of spiral arteries to control oxygenation and blood perfusion in the developing placenta
what is the function of endovascular EVT?
break down the maternal endothelium and underlying smooth muscle AND form new endothelial layer with EVT coating the inside
- to enable the de-spiralisation of the spiral arteries (for control of the oxygenation and blood perfusion of the placenta) -
how does endovascular EVT cause spiral artery remodelling?
the breakdown of the maternal endothelium and the underlying smooth muscle causes the spiral arteries to open up into straight channels
= change from being highly convoluted, high-pressure vessels TO low pressure, high capacity conduits for blood flow
how are the spiral arteries converted by endovascular EVT?
spiral arteries will de-spiralise and become open, straight channels (due to maternal endothelium and smooth muscle breakdown)
why is the conversion of spiral arteries by endovascular EVT important?
change from being highly convoluted, high-pressure vessels TO low pressure, high capacity conduits for increased blood flow
= to meet the increased demand for placental and foetal growth and haemotrophic nutrition in the second and third trimester
describe the change in spiral artery structure due to endovascular EVT
change from being highly convoluted, high-pressure vessels TO low pressure, high capacity conduits for blood flow
explain the change in spiral artery structure due to endovascular EVT
(from being highly convoluted, high-pressure vessels TO low pressure, high capacity conduits)
to increase blood flow to the developing placenta and fetus to keep up with increased growth rate and haemotrophic nutrition
why is it important that the spiral arteries are remodelled?
so when there is an increase in demand for blood by the developing placenta and fetus, the blood flow can be increased accordingly to meet the requirements for heterotrophic nutrition and increased growth
what do endovascular EVTs regulate?
regulate oxygenation and blood perfusion during early placental development
how do the endovascular EVTs regulate oxygenation of the placenta during histiotrophic nutrition?
plug maternal spiral arteries to maintain hypoxia and blood perfusion
= protects fetus and placenta from oxidative stress during development in the histiotrophic nutrition stage
how do the endovascular EVTs regulate oxygenation of the placenta in during haemotrophic nutrition?
the EVT plugs dissolve and blood perfusion and oxygenation of the placenta is restored allowing further development of the fetus and placenta
how does the type of fetal nutrition influence endovascular EVT action on the spiral arteries?
in histiotrophic nutrition = EVT plug the spiral arteries and prevent blood perfusion and oxygenation as nutrition is derived from the uterine glands and tissues
in haemotrophic nutrition = EVT plugs dissolve and the blood perfusion and oxygenation is restored as nutrition is derived from the maternal blood
how does EVT become endovascular EVT?
when the EVT cells coating the tertiary chorionic villi invade down into the spiral arteries, endovascular EVT is formed
where is endovascular EVT found?
coating the inside of the new, wider spiral arteries
which nutrients are exchanged across the placenta?
oxygen glucose water electrolytes calcium amino acids
how is oxygen exchanged across the placenta?
simple diffusion due to a steep diffusional gradient between the high maternal oxygen tension and the low fetal oxygen tension
how is glucose exchanged across the placenta?
facilitated diffusion by transporters on the maternal side and the fetal trophoblast cells
how is water exchanged across the placenta?
mainly by diffusion but there are some local hydrostatic gradients
(placenta is the main site of water exchange but some does occur at the amnion-chorion)
how are electrolytes exchanged across the placenta?
both diffusion and active (energy-dependent) co-transport
how is calcium exchanged across the placenta?
active transport via the magnesium-calcium ATPase pump
how are amino acids exchanged across the placenta?
reduce maternal urea excretion AND active transport of amino acids to fetus
how does pregnancy affect cardiac output in the mother?
maternal cardiac output increases by 30% during the first trimester
(i.e. increased stroke volume and heart rate)
how does pregnancy affect peripheral resistance in the mother?
maternal peripheral resistance decreases by up to 30%
how does pregnancy affect blood volume in the mother?
maternal blood volume increase by up to 40% near term
how does pregnancy affect pulmonary ventilation in the mother?
maternal pulmonary ventilation increases by up to 40%
what changes does the mother go through to meet the increased metabolic demand during pregnancy?
maternal cardiac output increases by up to 30%
(combined with a 30% decrease in peripheral resistance and a 40% increase in blood volume)
maternal pulmonary ventilation increases by up to 40%
how much glucose and oxygen does the placenta consume?
consumes 40-60% of the glucose and oxygen it is supplied
how does the composition of fetal blood compare to that of maternal blood?
fetal blood has a lower oxygen tension than maternal blood
but fetal and maternal oxygen saturation and content is similar
compare adult haemoglobin to fetal/embryonic haemoglobin
embryonic/fetal haemoglobin has a greater affinity for oxygen than adult haemoglobin so bind to oxygen more strongly
why is the altered structure of embryonic/fetal haemoglobin advantageous?
(HbF in fetal haemoglobin has a greater affinity for oxygen than HbA in adult haemoglobin so binds more strongly to oxygen)
= enables the transfer of oxygen from mother to fetus prenatally to meet the demands of the developing fetus
in which trimester do organ systems form?
first trimester
in which trimester do organ systems mature and develop?
second and third trimester
what is the initial circulatory system for the fetus in the first few weeks?
tube of mesoderm that pumps blood at day 22
by when does the fetus have a relatively complete circulatory system?
by the second trimester
where does gas exchange take place in the fetus?
placenta acts as the main site for gas exchange for the fetus (not lungs)
how do the ventricles act in the fetus as opposed to in a human?
ventricles pump in parallel rather than in series
how is the fetal circulatory system adapted for fetal development?
vascular shunts bypass hepatic and pulmonary circulation = permits the heart to drive oxygenated blood from the placenta to the developing tissues that require it the most (i.e. brain)
what is the function of the vascular shunts in the fetus?
bypass the hepatic and pulmonary circulation (to enable the direction of oxygenated blood to where demand is greatest)
how do the lung structures develop in the fetus?
lung bud develops around the forgut
then branches in the first trimester = to give other lung structures
when do the primitive air sacs form in the fetus?
approx week 20
when does lung vascularisation take place in the fetus?
approx week 28
when does surfactant production take place in the fetus?
approx week 20 (upregulated towards term)
how does surfactant production change towards term?
upregulated towards term
how does the foetus prepare for the breathing reflex?
spends 1-4 hours a day making rapid respiratory moments during REM sleep
what gives rise to the gastrointestinal system?
gut tube from the endoderm and yolk sac
when does the pancreas form during pregnancy?
pancreas fully functional at the start of the second trimester
(insulin secretion begins mid-second trimester)
when does the pancreas begin secretin insulin during pregnancy?
insulin secretion begins in the middle of the second trimester
how does glycogen deposition change towards term?
liver glycogen is progressively deposited and accelerated towards term
when does the fetal liver form during a pregnancy?
begins to form at approx day 23
what does the fetus do to the amniotic fluid?
fetus will inhale and swallow the amniotic fluid
what does the swallowing of the amniotic fluid by the fetus result in?
the ingested debris and bile acids will form the meconium (first stool)
what is the meconium?
the first stool of the newborn
what does the meconium consist of?
ingested amniotic fluid, debris (lanugo, intestinal cells and pancreatic enzymes) and bile salts and pigments
when do fetal movements begin?
in the late first trimester
when are fetal movements detectable by the mother?
approx by week 14
when does the fetus develop stress responses?
approx week 18
when does the fetus develop thalamus-cortex connections?
approx week 24
does the fetus show conscious wakefulness?
no - fetus is mostly in slow-wave or REM sleep most of the time
what are developmental changes in the fetus said to be orchestrated by?
simultaneous increase in fetal corticosteroids (towards the end of a pregnancy)
what is organ maturation coordinated by?
fetal corticosteroids
what is labour?
the process by which the fetus is safely expelled from the uterus at the correct time
what are three purposes of labour?
safe expulsion of the uterus at the correct time
expulsion of the placenta and the fetal membranes
resolution and healing of the uterus to permit future reproductive events
how does labour prepare the body for future pregnancies?
after the fetus, fetal membranes and placenta have been safelt expelled, the uterus undergo resolution and healing = preparing the uterus for future pregnancies
what is expelled during labour?
fetus, fetal membranes, placenta
what kind of reaction is labour?
pro-inflammatory reaction
what two occurrences make labour a pro-inflammatory reaction?
immune cell infiltration
cytokine and prostaglandin secretion
how many phases are there to labour?
four
name the four phases of labour
quiescence (phase 1)
activation (phase 2)
stimulation (phase 3)
involution (phase 4)
what is phase 1 of labour?
quiescence = prelude to parturition
what is phase 2 of labour?
activation = preparation for labour
what is phase 3 of labour?
stimulation = processes of labour
what is phase 4 of labour?
involution = parturient recovery
what happens during phase 1 of labour?
contractile unresponsiveness, cervical softening
uterus is quiet but some changes in cervix
what happens during phase 2 of labour?
uterine preparedness for labour, cervical ripening
cervical development for dilation
what happens during phase 3 of labour?
uterine contraction, cervical dilation, fetal and placenta expulsion (three stages of labour)
what happens during phase 4 of labour?
uterine involution, cervical repair, breast feeding
restores uterus to original size, repairs cervix and onset of lactation
what happens after phase 1 of labour?
initiation of parturition
what happens after phase 2 of labour?
onset of labour
what happens after phase 3 of labour?
delivery of conceptus
what happens after phase 4 of labour?
restoration of fertility
why does the uterus undergo resolution and healing after labour?
during pregnancy, the uterus undergoes a lot of expansion, tissue remodelling and distention = so to return uterus to original size and shape for future pregnancies
during labour, into where do immune cells infiltrate?
the cells of the female reproductive tract
what inflammatory molecules are secreted during labour?
prostagalndins and cytokines
why are cytokines and prostaglandins secreted during labour?
to orchestrate the timing and sequence of the events of labour
how many stages of labour are there?
three
name the stages of labour
first stage (split into latent phase and active phase)
second stage
third stage
differentiate between the phases and the stages of labour
there are four phases of labour (quiescence, activation, stimulation, involution)
there are three stages of labour (occur in the stimulation phase of labour)
what happens during the first stage of labour?
uterine contractions and cervical dilation
- slow dilation in the latent phase up to 2-3cm
- followed by rapid dilation to 10cm in the active phase
what happens during the second stage of labour?
delivery of the fetus
- commences at 10cm maximal cervical dilation
- maximal myometrial contractions
what happens during the third stage of labour?
delivery of the placenta
- expulsion of the placenta and fetal membranes
- post-pastum repai
what are the two segments of the first stage of labour?
latent phase (slow cervical dilation to 2-3cm)
active phase (rapid cervical dilation to 10cm)
how is cervical dilation spilt into segments?
slow cervical dilation to 2-3cm = latent phase
rapid cervical dilation to 10cm = active phase
what stimulates expulsion of the fetus?
maximal cervical dilation at 10cm
how does the rate of cervical dilation change?
initially slow up to 2-3cm and then rapid up to 10cm
what happens at maximal cervical dilation?
stimulates expulsion of the fetus
what is maximal cervical dilation?
at 10cm
how long is labour usually in the first delivery?
approx 8-18 hours
how long is labour usually last in the first delivery?
approx 8-18 hours
how long is labour usually last in subsequent deliveries after the first?
approx 5-12 hours
what is the key role of the cervix during pregnancy?
retains the fetus in the uterus during pregnancy
describe the structure of the cervix
bundles of collagen fibres that are embedded in a proteoglycan matrix
= high connective tissue content that provides rigidity and enables stretch resistance
why is it important that the cervix has a high connective tissue content?
provides cervical rigidity and ensures it is stretch-resistant
= to keep cervix closed
what are the structural changes that take place during cervical softening?
measurable changes in compliance but retains cervical competence
what are the four parts to cervical remodelling?
cervical softening
cervical ripening
cervical dilation
post-partum repair
when does cervical softening begin?
begins in the first trimester
what happens during cervical softening?
measurable changes in compliance but cervical competence is retained
what is cervical competence?
the ability of the cervix to stay closed and keep the fetus inside
when does cervical ripening begin?
weeks and days before birth
what happens during cervical ripening?
monocyte infiltration
IL-6 and IL-8 secretion
hyaluronic acid deposition
when does cervical dilation begin?
the ninth month of pregnancy, closer to the due date
what happens during cervical dilation?
increased hyaluronidase expression to break down deposited hyaluronic acid
matrix metalloproteinases decrease collagen content
why is hyaluronic acid deposited during cervical ripening?
to increase tissue water content = increases cervical ripening
why is hyaluronidase increasingly expressed during cervical dilation?
to increase the breakdown of the deposited hyaluronic acid
= contributes to increased cervical elasticity
what is the function of matrix metalloproteinases in cervical dilation?
decrease collage content to contribute to the increased cervical elasticity
what are MMPs?
matrix metalloproteinases
what happens during post-partum repair in cervix remodelling?
recovery of tissue integrity and competency
why does cervical ripening take place?
to allow extensive immune cell infiltration, IL6 and IL8 secretion and hyaluronic acid deposition into the uterus
why does cervical dilation take place?
to breakdown collagen and hyaluronic acid to increase cervical elasticity
why does cervical post-partum repair take place?
to prepare the cervix for future reproductive events
why is cervical remodelling important?
needs to soften cervix to allow dilation and let the fetus pass through, out of the uterus
what stimulates parturition?
the fetus determines the timing of partirition through changes in the fetal HPA axis
which hormone increases in maternal blood towards the end of pregnancy?
the CRH levels rise exponentially towards the end of pregnancy
why does CRH bioavailability increase towards the end of pregnancy?
there is a decline in CRH binding protein levels so CRH bioavailability increases towards the end of pregnancy
how do CRH and CRP-BP levels change towards the end of pregnancy?
while CRH-BP levels decrease, the CRH levels increase exponentially
what are the functions of fetal CRH in labour?
promotes fetal ACTH production and fetal cortisol release
increased fetal cortisol stimulates placental CRH production
increased fetal cortisol stimulates fetal adrenal DHEAS production = increased oestrogen production
describe the positive feedback loop triggered by fetal CRH
fetal CRH stimulates fetal adrenal cortisol production
fetal cortisol acts on the placent to stimulate placental CRH production
placental CRH positively feeds back to the fetal hypothalamus and stimulates fetal CRH production
how does fetal CRH affect the placenta?
stimulates fetal adrenal cortisol production
fetal cortisol acts on the placenta to stimulate placental CRH production
how does fetal CRH affect the fetal adrenal cortex?
stimulates the fetal adrenal cortex to produce cortisol
what is DHEAS?
dihydroepiandrosterone sulphate
what is the function of DHEAS?
acts as a substrate for oestrogen production in the placenta
how do progesterone levels vary throughout pregnancy?
increase steadily to very high levels and drop rapidly as term approaches
how do oestrogen levels vary throughout pregnancy?
increase steadily to moderately high levels and drop rapidly as term approaches
how do hCG levels vary throughout pregnancy?
increase rapidly to week 7 and fall rapidly and remain low by week 10
how does the serum oestrogen : progesterone ratio change as a pregnancy progresses?
serum O:P ration may shift in favour of oestrogen (possibility)
how does progesterone receptor expression change as term approaches?
as term approaches, there is a switch from PR-A isoforms (activating) to PR-B and PR-C isoforms (repressive) expressed in the uterus
what is functional progesterone withdrawal?
as term approaches, there is a switch from PR-A isoforms (activating) to PR-B and PR-C isoforms (repressive) expressed in the uterus
what are the activating isoforms of the progesterone receptor?
PR-A
what are the repressive isoforms of the progesterone receptor?
PR-B and PR-C
describe the shift in progesterone receptor isoforms
expression shifts from PR-A (activating) isoforms to PR-B and PR-C (repressive) isoforms in the uterus
how does oestogen receptor expression vary with pregnancy?
as term approaches, there is a rise on oestrogen receptor alpha expression
what is the impact of functional progesterone withdrawal on the uterus?
blinds the uterus to progesterone action and makes it increasingly sensitised to oestrogen action
why is it important that the uterus is blinded to progesterone action during labour?
high progesterone levels through pregnancy maintain uterine relaxation
so when progesterone withdrawal occurs = uterine relaxation cannot be maintained so uterine contraction can take place during labour
how does the progesterone receptor shift stimulate uterine contractions?
progesterone receptors shift from being activating to repressive so progesterone can no longer carry out its function of maintaining uterine relaxation
thereby allowing uterine contractions during labour (when there is a shift in receptor isoforms)
how does the uterus respond to changes in progesterone and oestrogen receptor expression?
uterus becomes blinded to progesterone action and more sensitised to oestrogen action
what is the function of progesterone during pregnancy?
maintains uterine relaxation
what type of hormone is oxytocin?
nonapeptide (9 AAs) hormone
what is a nonapeptide hormone?
a peptide hormone with nine amino acids
where is oxytocin synthesised?
mainly in the maternal pituitary gland and utero-placental tissues
when does uterine oxytocin production rapidly increase?
uterine oxytocin production rapidly increases at the onset of labour
(due to rise in oestrogen levels)
what drives the increase in uterine oxytocin secretion?
rise in oestrogen levels
what stimulates the release of oxytocin in the uterus?
promoted by vaginal stretch receptors (i.e. Ferguson reflex)
what is the Ferguson reflex?
as fetus starts to bear down on cervix and vagina, vaginal stretch receptors signal to hypothalamus
then hypothalamus signals onto the poster pituitary gland
oxytocin then released into the bloodstream
act on uterine myometrium to stimulate uterine contraction
what does oxytocin signal through?
G-protein coupled oxytocin receptors in the uterus
what type of receptors are oxytocin receptors?
G-protein couple dreceptors
what controls oxytocin receptor expression pre-labour?
increased progesterone levels pre-labour will inhibit oxytocin receptor expression
(so uterine relaxation can be maintained)
how does oxytocin receptor expression pre-labour affect the uterus?
pre-labour, less OXTR expression (due to elevated progesterone) so the uterus remains relaxed (i.e not contracting)
describe the change in uterine oxytocin receptor expression that takes place as term approaches
uterine OXTR expression increases greatly
explain the change in uterine oxytocin receptor expression that takes place as term approaches
during labour, progesterone levels fall + oestrogen levels rise = so uterine OXTR expression increases greatly
what are the functions of oxytocin in the uterus?
increases connectivity of the myocytes in the myometrium (syncitium formation)
destabilises membrane potentials so there is a lower threshold for muscle contraction
enhances liberation of intracellular Ca2+ ion stores for muscle contraction
(also stimulates prostaglandin release via uterine OXTR signalling pathways)
how and why does oxytocin affect the myometrium?
increases connectivity of the myocytes in the myometrium (syncitium formation)
- oxytocin promotes the formation of gap junctions between myocytes so the myometrium is more connected (i.e. can act as a syncitium)
how does oxytocin affect muscle contraction?
destabilises membrane potential to lower the threshold for muscle contraction
enhances the liberation of intracellular Ca2+ ion stores for muscle contraction
= increasing myometrial contractions
which hormone dominates most of a pregnancy?
progesterone
how does high progesterone affect oxytocin receptor expression pre-labour?
elevated progesterone levels will inhibit myometrial OXTR expression pre-labour to maintain uterine relaxation
how does high oestrogen affect oxytocin receptor expression pre-labour?
rapidly increased oestrogen levels will stimulate OXTR expression in the myometrium (during labour) when uterine relaxation is no longer necessary and uterine contraction must occur
what are the primary prostaglandins synthesised during labour?
PGE2, PGF2alpha, PGI2
what stimulates prostaglandin action in the uterus?
rising oestrogen levels drive prostaglandin action in the uterus
how do rising oestrogen levels stimulate prostaglandin action in the uterus?
- activate phospholipase A2 enzyme, generating more arachidonic acid for prostaglandin synthesis
- stimulates OXTR expression which promotes prostaglandin release through oxytocin signalling
what is the function of PGE2?
cervical remodelling (especially cervical softening and ripening)
how does PGE2 carry out its function?
promotes leukocyte infiltration, IL8 secretion and collagen bundle remodelling
what is the function of PGF2alpha?
stimulates myometrial contractions
how does PGF2alpha carry out its function?
promotes the connectivity of myocytes (together with oxytocin)
destabilises membrane potentials to lower the threshold for muscle contraction
what is the function of PGI2 and how is this carried out?
uterine relaxation
promotes myometrial smooth muscle relaxation and relaxation of the lower uterine segment (*between contractions)
what do prostaglandins work in conjunction with?
oxytocin
why is the function of PGI2 essential?
stimulate myometrial relaxation between contraction to allow blood to flow back to the uterus and placenta = to maintain blood flow to the fetus
why is the function of PGI2 essential?
stimulate myometrial relaxation between contractions to allow blood to flow back to the uterus and placenta = to maintain blood flow to the fetus
how does DHEAS affect oestrogen levels?
as DHEAS acts as a substrate for oestrogen production, increased DHEAS stimulates increased placental oestrogen levels
what do rising oestrogen levels cause?
increased oxytocin release from the PPG and the utero-placental tissues
upregulation of uterine OXTR
what does placental oestrogen stimulate?
upregulation of uterine OXTR
which hormone upregulates oxytocin receptor expression in the uterus?
oestrogen
which hormone inhibits oxytocin receptor expression in the uterus?
progesterone
how does oxytocin act in the uterus?
stimulates myometrial connectivity
stimulates more vigorous muscle contraction (destabilising membrane potentials + enhanced intracellular calcium release)
! stimulates prostaglandin release via the uterine OXTR !
what does increased oxytocin result in the production of?
increased prostaglandin relelase (via uterine OXTR signaling pathways)
to what do vigorous myometrial contraction feedback positively?
more vigorous muscle contractions in the uterus
= 1) increased prostaglandin production
= 2) increased oxytocin secretion
how is the uterus sensitised to the pituitary production of maternal oxytocin?
upregulation of uterine OXTR expression (towards term) = stimulates muscle contraction
(vaginal stretch receptors also stimulate oxytocin release via Ferguson reflec)
what stimulates syncitium formation in the uterus?
oxytocin release (following rising oestrogen levels) stimulates increased myometrial myocyte connectivity
where do myometrial contraction start and how do they progress?
start from the myometrial syncitium in the fundus and spread down the upper segment
(remain in the upper uterine segment)
what is the effect of only the upper myometrial segment contraction?
the myometrial syncitium of the fundus causes the contractions to be transmitted down the upper segment
= pulls up the cervix and lower segment to create one large birth canal for the foetus to transit out of
describe the type of myometrial contraction during labour
brachystatic (i.e. the muscle fibres do not relax completely and retain some muscle shortening)
define brachystatic
the muscle fibres do not relax completely and retain some muscle shortening (i.e. do not return to full length on relaxation)
what is the effect of the brachystatic myometrial contraction of the shape of the uterus?
as muscle fibres do not relax completely and retain some muscle shortening = the cervix progressively opens until complete dilation is achieved
which part of the uterus actively takes part in myometrial contractions?
upper segment
syncitium of myometrial muscle cells w extensive gap junctions in between
which part of the uterus passively takes part in myometrial contractions?
lower segment
explain the process of fetal expulsion
head engages w the pelvic space at 34-38 weeks
pressure on hind of fetus and head causes chin to press against chest (Flexion)
fetus rotates so fetal belly faces maternal spine
head expelled and then shoulders delivers sequentially followed by torso
(then much quicker expulsion of rest of the body)
when does the fetal head engage with the pelvic space?
at approx 34-38 weeks
how does pressure change within the uterus to cause fetal expulsion?
pressure on hind of fetus due to myometrial contraction AND pressure of fetal head on the cervix
= causes flexion of fetal head forward towards chest and rotation (prepped for expulsion)
what must occur before the fetus is expelled from the uterus?
must rotate so the fetal belly faces the maternal spine
how is the fetus expelled from the uterus?
head expelled first
shoulders delivered sequentially
torso and then rest of the body (much quicker)
what happens to the uterus after the fetus has been expelled?
uterus shrinks rapidly after fetal delivery (causing the area of contact between the placenta and the endometrium to shrink)
but uterus remains contracted (to prevent inter-uterine bleeding)
what does uterine shrinkage in turn cause?
- causing the area of contact between the placenta and the endometrium to shrink
- causing the folding of fetal membranes so they peel off the endometrium
why is the umbilical cord clamped after birth?
to stop fetal blood flow to the placenta
what is the impact of clamping the umbilical cord after birth?
= villi collapse
= haematoma forms between decidua and placenta
= subsequent contractions expel the placental and fetal membranes
what stimulates the contractions that cause expulsion of the placenta and fetal membranes?
clamping of the umbilical cord = villi collapse and then haematoma formation between the decidua and placenta = leads to contractions
what happens when the placental villi collapse when their blood supply is cut off?
heamatoma forms between the decidua and placenta
what are the layers of the uterus immediately post expulsion of the fetus?
amnion
chorion
decidua vera
myometrium
why does the uterus remain contracted after delivery?
to prevent inter-uterine bleeding
to facilitate thrombosis and healing of the blood vessels
how is the risk of inter-uterine bleeding post-delivery prevented?
the uterus remains contracted even after delivery
why do uterine involution and cervical repair occur?
to restore the non-pregnant state
why do uterine involution and cervical repair occur?
to restore the non-pregnant state
shielding uterus from commensal bacteria that live in the female reprodcutive ttract
restore endometrial cyclicity in response to hormones
