Pregnancy, Parturition and Late Fetal Development

Question 1

how much embryonic growth occurs in the first trimester

why

Answer 1

very limited amount growth- surprising considering the change from single celled zygote to complex embryo with body plan + major organ systems in place

embryo is dependent on histiotrophic nutrition in the 1st trimester = derivation of nutrients from the breakdown of surrounding endometrial tissues + from uterine gland secretions (uterine milk)

Question 2

give example of histiotrophic nutrition

Answer 2

peri-implantation period

syncytiotrophoblasts → invading endometrium surrounding embryo → breaking down the tissues + capillaries → the breakdown products fuel embryo development

also receiving nutrition from uterine gland secretion

and syncytiotrophoblasts are breaking down maternal capillaries → allows them to get some nutrition from maternal blood (but fetal membranes are not in contact with maternal blood)

Question 3

how does rate of fetal growth change from 1st to 2nd trimester

why

Answer 3

significantly increases

change from histiotrophic nutrition to hemotrophic nutrition at the start of 2nd trimester

haemotrophic nutrition = fetus derives its nutrients from the maternal blood

Question 4

how is haemotrophic nutrition achieved in humans

Answer 4

humans have a haemo-chorial type placenta - maternal blood is directly in contact with the fetal membranes (chorion)

Question 5

what specific event causing the switch in nutrition between the 1st and 2nd trimester

Answer 5

activation of the haemo-chorial type placenta around the 12th week of gestation

allows the switch from histiotrophic to haemotrophic nutrition (large increase in fetal growth can now occur)

Question 6

what is the amnion

Answer 6

amnion is derived from epiblasts

other epiblast derived cells form the fetus

amnion is the first of the fetal membranes and forms roof of amniotic cavity which will become amniotic sac

Question 7

how does the amnion contribute to amniotic sac formation

Answer 7

from 5th week of gestation amniotic cells secrete fluid into the amniotic cavity causes it to expand and start to form sac which encapsulates and protects the fetus

as the amniotic sac expands with fluid accumulation → forces amnion into contact with chorion → they fuse → forms amniotic sac

Question 8

what are the fetal membranes

Answer 8

extra-embryonic tissues which form a tough but flexible amniotic sac which encapsulates the fetus and forms the basis of the maternal fetal interface

amnion - innermost

chorion - outermost membrane

allantois - grows along connecting stalk from embryo to chorion

Question 9

what is the connecting stalk

Answer 9

extra embryonic structure which connects the chorion to the embryo

Question 10

what are the trophoblastic lacunae

how do they form

Answer 10

large spaces surrounding the embryo unit which are filled with maternal blood

syncytiotrophoblasts break down maternal capillaries + uterine glands → lumens of the capillaries and glands fuse → create continuous space through which maternal blood can flow and come into contact with syncitiotrophoblast

they become filled with maternal blood as they develop → later become intervillous spaces

Question 11

label the diagram

Answer 11

Question 12

what are the fetal membranes derived from

what do they form

Answer 12

amnion:
derived from epiblasts
forms closed, avascular sac with developing embryo at one end

chorion:
derived from yolk sac and trophoblasts
highly vascularized
forms chorionic villi - outgrowths of cytotrophoblasts which form basis of fetal side of placenta

allantois:
derived from yolk sac
becomes coated in mesoderm + vascularizes to form umbilical cord
might be part of embryonic bladder

Question 13

what is the structure of the amniotic sac

Answer 13

2 layers which are fused together

amnion on inside

chorion on outside

Question 14

what forms the umbilical cord

Answer 14

combination of connecting stalk, allantois and the mesoderm which coats it

as the allantois grows along connecting stalk it becomes coated in mesoderm which then becomes vascularized = umbilical cord

Question 15

how are cytotrophoblasts relevant in placenta development

Answer 15

(remember trophoblast divided into invasive syncytiotrophoblast and proliferative cytotrophoblast which give rise to more syncytiotrophoblasts)

continues to provide cells which will form syncytiotrophoblasts

outgrowths of cytotrophoblasts form (cytotrophoblast layer sits on outside of chorion)

the outgrowths are finger like projections through syncytiotrophoblast layer into maternal endothelium = primary chorionic villi

Question 16

label the image

what direction do the outgrowths grow

Answer 16

Question 17

what is the function of the chorionic villi

Answer 17

provide a large surface area for exchange of gases+nutrients etc between the mother and fetus

Question 18

describe the development of chorionic villi

what is the function of this

Answer 18

primary phase - outgrowths of cytotrophoblasts form which then undergo branching

secondary phase - growth of the fetal mesoderm into the primary chorionic villi

tertiary phase - growth of umbilical artery and vein into the mesoderm within the villus, provides vasculature

the villi grow into the maternal blood spaces → allows close contact between maternal and fetal blood for exchange, the villi provide large surface area for exchange

Question 19

what is the structure of the terminal chorionic villi

why

Answer 19

blood vessel is a convoluted knot of vessels with some areas of dilatation

this slows down the bloodflow through the terminal villus - gives time for exchange between maternal and fetal blood

Question 20

how does the structure of chorionic villus change over pregnancy

Answer 20

early in pregnancy:
villi have large diameter 150-200 micrometres
thick layer of trophoblasts separating fetal capillaries and maternal blood is around 10 micrometres thick

later in pregnancy:
villi diameter has decreased to 40 micrometres
capillaries within villi move so that layer of trophoblasts separating them from maternal blood is 1-2 micrometres

much shorter diffusion distance later in pregnancy

Question 21

describe the maternal blood supply to the endometrium

Answer 21

ovarian and uterine artery fuse and give rise to number of branches of arcuate arteries (in the myometrium)

arcuate arteries then give rise to radial arteries (which pass through myometrium and stop at junction of endometrium)

radial arteries branch further to form basal arteries

basal arteries form spiral arteries

Question 22

how does the blood supply to the endometrium vary depending on implantation

Answer 22

during menstruation the basal arteries grow and spiralise to form spiral arteries → supply blood to thickened endometrium → if implantation does not occur there is vasoconstriction + regression of these spiral arteries → endometrium is shed

if implantation does occur → spiral arteries are stabilised and provide maternal blood supply to fetus (in intervillous space)

Question 23

label the diagram

which vessels may not always be present

why

Answer 23

spiral arteries - depending on stage of menstrual cycle or if pregnant

if pregnant or in luteal/proliferative and secretory phase = present

menstruation = not present

Question 24

how do the spiral arteries change after implantation

Answer 24

they undergo extensive remodelling during placental development = conversion

extra-villus trophoblasts (on the outside of the villi) start to invade down into maternal spiral arteries → forms endovascular extra-villus trophoblasts, by doing the capillaries de-spiralise and open up to form straight channels

as the endovascular EVT forms it breaks down the maternal endothelium of the spiral arteries and the underlying smooth muscle and forms a new endothelium made up of EVT cells

conversion = process by which spiral arteries are changed from highly convoluted, high-pressure vessels into lower pressure, straighter, high capacity conduits

allows large flow of blood into the maternal blood spaces

Question 25

summarise conversion why is it clinically relevant

Answer 25

change of spiral arteries to non-spiral, low pressure, high capacity conduits problems in conversion are thought to underlie IUGR and pre-eclampsia

Question 26

what do the spiral arteries do in pregnancy

Answer 26

they supply the maternal blood spaces/intervillous spaces with blood → exchange of gases and nutrients with fetus then occurs through villus

Question 27

label this structure describe the exchange occurring

Answer 27

spiral arteries fill intervillous spaces/maternal blood spaces with maternal blood (some of the blood drains away in the venous system) substances can be exchanged with fetus across their highly vascularized chorionic villi - large surface area for exchange between maternal blood + chorionic villi

Question 28

what are the possible mechanisms for nutrient exchange across the placenta

Answer 28

simple diffusion - depends on size, shape, charge of molecule + concentration gradient facilitated diffusion - depends on number of transporters + concentration gradient active transport - depends of energy-dependent co-transporters

Question 29

what are the main molecules crossing the placenta how do they do it

Answer 29

Question 30

what changes to the maternal circulation occur during pregnancy

Answer 30

Question 31

what are the metabolic demands of the placenta

Answer 31

very high placenta itself consumes 40-60% of the O2 and glucose supplied by the maternal blood

Question 32

what is the O2 partial pressure in the fetus what are the implications of this

Answer 32

oxygen partial pressure in fetus is much lower than in maternal this would suggest that fetal Hb saturation would be much lower than maternal but fetal saturation and O2 content is very similar to maternal this is because the embryo and fetus have different forms of haemoglobin which have higher O2 affinity than adult/maternal haemoglobin

Question 33

what are the features of the cardiovascular system in the 2nd and 3rd trimester

Answer 33

(organ systems are in place by end of 1st trimester, but they mature and develop in 2nd and 3rd) complete circulatory system in place by the end of 1st trimester but some major differences compared to CV system in neonates: placenta acts as site of gas exchange (not lungs) ventricles act in parallel rather than in series → driving blood together around the same circulatory loop → achieved by presence of vascular shunts which bypass pulmonary and hepatic circulation (close at birth) shunts allow body to drive oxygenated blood from around the body more efficiently, especially to head → ensures that it is well oxygenated + has nutrients needed for tissue development

Question 34

what are the features of the respiratory system in the 2nd and 3rd trimesters

Answer 34

(was a bud around the foregut in 1st trimester → branched) 20 weeks - primitive air sacs form + production of surfactant starts and then increases rapidly close to term 28 weeks - lungs become vascularized fetus spends 1-4hr/day making rapid respiratory breaths during REM sleep - practice for breathing reflex + important for diaphragm development remember lungs are not site of gas exchange, placenta is

Question 35

what are the features of the gastrointestinal system in the 2nd and 3rd trimesters

Answer 35

start of 2nd trimester - developing pancreas which is functional and secretes insulin from the middle of the 2nd trimester progressive development of liver - significant glycogen deposition, especially close to delivery fetus swallows large amounts of amniotic fluid in utero - together with debris, bile acids forms meconium (first stool after birth)

Question 36

what are the features of the nervous system seen in 2nd and 3rd trimester

Answer 36

fetal movements began late in 1st trimester, detectable by mother from 14 weeks (early 2nd trimester) stress responses from 18 weeks onwards, but thalamus-cortex connections form by 24 weeks (sensory inputs can then be processed) fetus does not show conscious wakefulness in utero - in slow-wave or REM sleep

Question 37

what stimulates organ maturation as pregnancy progresses

Answer 37

increase in fetal corticosteroids towards end of pregnancy → responsible for the final maturation of each of the organ systems exponential increase in corticosteroids → increased surfactant production + liver glycogen deposition

Question 38

what are the aims of labour

Answer 38

safe expulsion of fetus at correct time expulsion of placenta and fetal membranes (so uterus is empty to allow next pregnancy) healing of uterus to allow future reproduction

Question 39

what cellular changes are seen in labour why

Answer 39

it is a pro-inflammatory process: extensive immune cell infiltration into tissues of reproductive tract large production of inflammatory cytokines and prostaglandins - important in orchestrating timing and sequence of events in labour

Question 40

what are the phases of labour

Answer 40

Phase 1 - Quiescent: Late in 1st trimester onwards uterus is not contracting but there are some cervical changes Phase 2 - Activation some uterine activity further cervical developments → preparations for cervix to dilate Phase 3 - Stimulation uterine contraction cervical dilation 3 stages of labour occur Phase 4 - Involution uterine involution - restored to its original size repair of cervix start of lactation

Question 41

what are the stages of labour what phase do they occur in

Answer 41

3rd Phase

Question 42

what is the timing of the stages of labour

Answer 42

1st stage - contractions and cervical dilation = 14 hours much longer than stages 2 and 3 separated equally between latent and active phases 2nd stage = 1-2 hours fetal descent and delivery 3rd stage = 1-2 hours placenta delivery 1st delivery = overall takes 8-18 hours 2nd delivery = 5-12 hours

Question 43

when does the 2nd stage of labour begin what happens in it

Answer 43

when the cervix is fully dilated at 10cm descent + delivery of fetus maximal myometrium contractions

Question 44

what happens in the 1st stage of labour

Answer 44

uterine contractions start and cervix dilates split equally into latent and active phases latent - slow cervix dilation to 2-3cm active - fast cervix dilation to 10cm

Question 45

what happens int he 3rd stage of labour

Answer 45

delivery of placenta and fetal membranes post-partum repair

Question 46

how does cervix structure reflect its roles in pregnancy

Answer 46

pregnancy: cervix has essential role in retaining fetus in the uterus therefore cervix has high connective tissue content - provides rigidity, is stretch resistant → keeps cervix closed structure is bundles of collagen fibres within cervical tissue which are then embedded in proteoglycan matrix remodelling: cervix needs to be softened to allow dilation to allow delivery of fetus remodelling of collagen bundles → softening of cervix

Question 47

how does the cervix undergo remodelling

Answer 47

**Softening begins in 1st trimester:** maintains cervical competence (stays closed) but it has has a measurable change in compliance **days or weeks before birth Ripening occurs:** extensive monocyte (macrophages and neutrophils) infiltration into cervix and IL-6 and IL-8 secretion hyaluronan deposition **when labour starts cervical dilation occurs:** increased hyaluronidase expression → breaks down hyaluronan deposited in ripening immune cell influx → production of large amounts of matrix metalloproteinases → breakdown collagen → increase elasticity **post-partum repair:** recovery of tissue integrity + competence (ensures women is able to go through pregnancy again with closed cervix which can then undergo remodelling around birth)

Question 48

what is the endocrine regulation of labour

Answer 48

not sure of the exact mechanism - current thinking is fetus determines timing of delivery through changes in the hypothalamo-pituitary-adrenal axis close to birth there is an exponential increase in production of CRH by fetal pituitary and a concomitant decrease in production of CRH binding protein → increased bioavailability of CRH increased CRH → stimulates ACTH release → acts on fetal adrenal cortex → stimulates cortisol release cortisol binds to placenta → drives placental production of CRH → placental CRH acts on fetus to further increase cortisol production (+ve feedback) CRH also stimulates production of DHEAS by fetal adrenal cortex → DHEAS is used as a substrate to allow greater oestrogen production by placenta

Question 49

describe progesterone levels during pregnancy why is this necessary describe estrogen levels during pregnancy

Answer 49

progesterone levels increase steadily during pregnancy progesterone is produced by placenta - high levels are needed to maintain pregnancy + uterine relaxation until labour occurs (falls following delivery) estrogen levels also increase steadily during pregnancy increased estrogen : progesterone ratio close to term (but over pregnancy more progesterone than estrogen)

Question 50

what happens to estrogen and progesterone levels during labour

Answer 50

approaching delivery there is a switch in progesterone receptor subtypes expressed on the uterus switch from A isoforms (activating) to B and C isoforms (repressive) leads to functional progesterone withdrawal → levels of progesterone are still high but change in receptor isoforms means that the uterus is **blinded to the action of progesterone** at the same time there is an increase in estrogen receptor alpha expression in uterine tissue leads to uterus becoming **sensitised to estrogen** action ultimately leads to local shift in estrogen : progesterone ratio in uterine tissues - increased ratio (more estrogen less progesterone)

Question 51

what is the result of increased estrogen to progesterone ratio close to birth

Answer 51

increased sensitivity of uterus to estrogen + estrogen production: increased levels of estrogen produced by placenta promote local uterine production of oxytocin but main cause of sharp increase in oxytocin levels before birth is ferguson reflex → stimulates oxytocin production from posterior pituitary progesterone normally inhibits production of oxytocin receptor on uterus to allow it to stay relaxed, but increased estrogen sensitivity → large increase in OTR expression → myometrium becomes sensitised to oxytocin

Question 52

what is the ferguson reflex

Answer 52

fetus begins to bear down on cervix stretch receptors in cervix and vagina signal to hypothalamus hypothalamus stimulates posterior pituitary to release oxytocin into maternal circulation oxytocin acts on myometrium to cause contraction

Question 53

where does oxytocin bind to once release why is this significant

Answer 53

oxytocin binds to G protein coupled oxytocin receptor (OTR) on myometrium OTR receptors expression is inhibited pre-birth by oxytocin the sensitization of uterus to estrogen + rise in production as term approaches → large increase in OTR expression → allows the myometrium to be sensitive to estrogen

Question 54

how does progesterone maintain uterine relaxation

Answer 54

inhibits expression of oxytocin receptor on uterus → means that the myometrium is not sensitive to oxytocin so will not contract if it is released

Question 55

where is oxytocin produced

Answer 55

9aa hormone produced in utero-placental tissues but mainly posterior pituitary

Question 56

what is the effect of oxytocin

Answer 56

increases connectivity of myocytes in myometrium - promotes formation of gap junctions to form a syncytium destabilised membrane potentials to lower the threshold for contraction promotes liberation of intracellular Ca2+ stores within myometrial cells

Question 57

what stimulates release of prostaglandins in labour

Answer 57

rising estrogen levels drive prostaglandin production in 2 ways: rising estrogen activates phospholipase A2 enzyme → generates more arachidonic acid for PG synthesis estrogen stimulation of oxytocin receptor expression promotes PG release (through oxytocin signalling)

Question 58

what are the effects of prostaglandin release

Answer 58

PGE₂ - acts on cervix PGF₂alpha - acts on myometrium PGI₂ - acts on myometrium

Question 59

draw flow chart of the regulation of labour

Answer 59

Question 60

explain the process of myometrial contraction

Answer 60

myocytes in upper uterine segment formed a syncytium (due to oxytocin binding) → gap junctions allow the contractions to be transmitted across the whole upper segment contractions start at fundus → spread down upper segment → action of the contractions it to pull up + apart the lower segment + cervix → forms open birth canal (cervix is dilated and lower segment is passive) lower segment + cervix are pulled up because the contractions are brachystatic - after contraction the muscle fibres do not become completely relaxed, so they retain some shortening (don't return to full length on relaxation) each contraction progressively pulls the lower segment + cervix up and apart until full 10cm dilation is reached (birth canal is formed)

Question 61

describe the process of fetal expulsion from uterus

Answer 61

head engages with cervix at 34-38 weeks onset of labour - myometrial contractions put pressure on hindquarters of fetus + pressure of head on cervix → head flexion = causes chin to press against chest as labour progresses - fetus rotates, so that belly faces mother's spine → head is expelled first after cervical dilation → shoulders are delivered sequentially (upper first) → torso (once shoulders are out fetus is delivered quite quickly)

Question 62

how are the placenta and fetal membranes delivered

Answer 62

rapid shrinkage of uterus after fetus has been delivered → area of contact of placenta with endometrium starts to shrink at the same time uterine shrinkage causes folding of fetal membranes (which were stretched before) → fetal membranes peel off endometrium umbilical cord is clamped after birth → stops fetal blood flow to placenta → chorionic villi collapse → haematoma formation between decidua and placenta haematoma + ongoing myometrial contractions → expel placenta + fetal membranes from uterus

Question 63

what happens after the placenta and fetal membranes have been delivered why

Answer 63

Uterus remains contracted after delivery to facilitate uterine vessel thrombosis → prevents intra uterine bleeding Uterine involution and cervix repair restore non-pregnant state → important because it stops: commensural bacteria in reproductive tract from entering up into uterus Restore endometrial cyclicity in response to reproductive hormones to allow implantation of another embryo