Pregnancy, Parturition and late foetal development:

Question 1

how is fetus nutrition provided?

Answer 1

• early- histiotrophic
  
  • reliant on uterine gland secretions and breakdown of endometrial tissues
• switch at start of 2nd trimester- haemotrophic
  
  • achieved through a haemochorial- type placenta where maternal blood directly contacts the fetal membranes (chorion)

Question 2

what are the fetal membranes

Answer 2

extraembryonic tissue that forms a tough but flexible sac

encapsulates the fetus and forms the basis of the maternal-fetal interface

Question 3

what are the types of fetal membrane?

Answer 3

amnion (inner fetal membrane)

chorion (outer fetal membrane)

allantois

Question 4

what is the amnion?

Answer 4

arises from the epiblast (does not contribute to the fetal tissues)

forms a closed, avascular sac with the developing embryo at one eld

begins to secrete amniotic fluid for 5th week- forms a fluid-filled sac that encapsulates and protects the fetus

Question 5

what is the chorion

Answer 5

outer fetal membrane

• Outer membrane surrounding 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

Question 6

what is the allantois?

Answer 6

• 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.

Question 7

how does the amniotic sac form?

Answer 7

Expansion of the amniotic sac by fluid accumulation forces the amnion into contact with the chorion, which fuse, forming the amniotic sac

Question 8

what is the composition of the amniotic sac?

Answer 8

2 layers

amnion on inside

chorion on outside

Question 9

what is the makeup of the placenta?

Answer 9

Question 10

what are primary chorionic villi formed from?

Answer 10

cytotrophoblast

forms finger-like projections through syncytiotrophoblast layer into maternal endometrium

Question 11

what is the use for primary chorionic villi?

Answer 11

provide substantial surface area for exchange

Question 12

what are the phases of chorionic villi developement?

Answer 12

3 phases:

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.

Question 13

what is the terminal villus microstructure?

Answer 13

• convoluted know of vessels and vessel dilation
• slows blood flow enabling exchange between maternal and fetal blood
• whole structure coated with trophoblast
• change through pregnancy
  
  • in late pregnancy are thinner with less trophoblast separation from maternal blood
  • this allows reduction in transfer distance later in pregnancy

Question 14

how is maternal supplied to endometrium?

Answer 14

• Uterine artery branches give rise to a network of arcuate arteries.
• Radial arteries branch from arcuate arteries, and branch further to form basal arteries.
• Basal arteries form spiral arteries during menstrual cycle endometrial thickening.

Question 15

what is the function of spiral arteries?

Answer 15

provide the maternal blood supply to the endometrium

Question 16

how do spiral arteries re-model?

Answer 16

• 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 (replace maternal endothelium/SM)
• Conversion: turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow.

Question 17

what is the structure of the placenta?

Answer 17

Question 18

how does oxygen transport to fetus?

Answer 18

diffusional gradient (high maternal O2, low fetal O2 tension)

Question 19

how does glucose transfer to fetus?

Answer 19

facilitated diffusion by transporters on maternal side and fetal trophoblast cells

Question 20

how does water transfer to fetus?

Answer 20

placenta main site of exchange

some crosses amnion-chorion

majority by diffusion, some local hydrostatic gradients

Question 21

how do electrolytes transport to fetus?

Answer 21

large traffic of sodium and other electrolytes across the placenta

combination of diffusion and active energy dependant co-transport

Question 22

how does calcium transport to fetus?

Answer 22

actively transported across a concentration gradient by magnesium APTase calcium pump

Question 23

how do amino acids transport to fetus?

Answer 23

reduced maternal urea excretion and active transport of amino acids to fetus

Question 24

how does maternal supply change during pregnancy?

Answer 24

• 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%

Question 25

what does the placenta and fetus absorb from maternal supply?

Answer 25

* 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

Question 26

how does the circulatory system mature in late fetal development

Answer 26

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

Question 27

how does the respiratory system develop?

Answer 27

primitive air sacs form in the lungs around 20 weeks vascularisation from 28 weeks surfactant production begins around week 20, upregulated towards term fetus spends 1-4hrs/day making rapid respiratory movements during REM sleep

Question 28

how does the GI system develop in late fetal development?

Answer 28

endocrine pancreas functional from start of 2T- insulin from mid-2T liver glycogen progressively deposited- accelerates towards term large amounts to amniotic fluid swallowed- debris and bile acids form meconium

Question 29

how does the nervous system develop in late fetal development?

Answer 29

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

Question 30

what is organ maturation coordinated by?

Answer 30

fetal corticosteroids

Question 31

what is the point of labour?

Answer 31

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 pro-inflammatory reaction

Question 32

how does labour have the characteristics of pro-inflammatory reaction?

Answer 32

immune cell infiltration inflammatory cytokine and prostaglandin secretion

Question 33

what are the phases of labour?

Answer 33

quinescence activation stimulation involution

Question 34

what are the 3 stages of labor?

Answer 34

* all occur in phase 3 of labour * first stage * contractions start * cervix dilated * latent phase (slow dilation of cervix to 2-3 cm) * active phase (rapid dilation of cervix to 10cm) * second stage * deliver of fetus * commences at full dilation of cervix * maximal myometrial contractions * third stage * delivery of placenta * expulsion of placenta and fetal membranes * post-partum repair

Question 35

how long does first delivery take?

Answer 35

8-18 hours

Question 36

how long do subsequent deliveries take?

Answer 36

5-12 hours

Question 37

how does the cervix change during pregnancy?

Answer 37

remodeling of cervix occurs * 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.

Question 38

how is labour initiated?

Answer 38

* Fetus determines timing of parturition through changes in fetal HPA axis * CRH levels rise exponentially towards end of pregnancy * Decline in CRH binging protein levels, so CRH bioavailability increases

Question 39

what are the functions of CRH in labour?

Answer 39

* 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

Question 40

what are the levels of progesterone and estrogen in labour?

Answer 40

* High progesterone through pregnancy maintains uterine relaxation * Serum estrogen:progesterone ratio *may* shift in favour of estrogen – this is unclear * 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.

Question 41

what is the role of oxytocin in labour?

Answer 41

* NonapeHSptide (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

Question 42

what are the functions of oxytocin in labour?

Answer 42

* Increases connectivity of myocytes in myometrium (syncytium) * Promotes formation of gap junctions to myometrium can act as a syncytium * Destabilise membrane potentials to lower threshold for contraction * Enhances liberation of intracellular Ca2+ ion stores

Question 43

what are the primary prostaglandins synthesised in labour?

Answer 43

PGE2 PGF2alpha PGI2

Question 44

how do estrogen levels drive prostaglandin action in uterus in labour?

Answer 44

* Rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis * Estrogen stimulation of oxytocin receptor expression promotes PG release.

Question 45

what do prostaglandins do during labour?

Answer 45

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 segment Other factors: peptide hormone relaxin and nitric oxide (NO) implicated in cervix re-modelling

Question 46

what is the hypothesis for the regulation of labour?

Answer 46

Question 47

how do myometrial contractions cause the formation of the birth canal?

Answer 47

* 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

Question 48

what happens to the uterus after fetal delivery?

Answer 48

rapid shrinkage of uterus causing area of contact of placental with endometrium to shrink also causes folding of fetal membranes- peel off the endometrium

Question 49

what is the effects of clamping of the umbillical cord after brith?

Answer 49

stops fetal blood flow to placenta -\> villi collapse hematoma formation between decidua and plaenta contractions expel placenta and fetal tissues

Question 50

what state does the uterus remain in after delivery?

Answer 50

contracted to facilitate uterine vessel thrombosis uterine involution and cervix repair restore the non-pregnant state, shielding uterus from commensural bacteria and restore endometrial cyclicity in response to hormones

Question 51

how does expulsion of the fetus occur?

Answer 51