Late Foetal Development

Question 1

How does the circulatory system mature?

Answer 1

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 2

How does the Respiratory system mature?

Answer 2

Primitive air sacs form in lungs around 20 weeks, vascularization from 28 weeks
Surfactant production begins around week 20, upregulated towards term
Fetus spends 1-4h/day making rapid respiratory movements during REM sleep

Question 3

How does the GI system mature?

Answer 3

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

Question 4

How does the Nervous system mature?

Answer 4

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 5

What do we think brings upon these maturation changes?

Answer 5

Increase in Corticosteroids in Foetus

Question 6

What happens in the process of Labour?

Answer 6

Safe expulsion of the fetus at the correct time
Expulsion of the placenta and fetal membranes
Resolution/healing to permit future reproductive events

Question 7

What type of reaction is Labour?

Answer 7

Labour has the characteristics of a pro-inflammatory reaction
Immune cell infiltration
Inflammatory cytokine and prostaglandin secretion

Question 8

What are the 4 Phases of labour?

Answer 8

Phase 1 - Quiescent, prelude to partition, contractile unresponsiveness, cervical softening.

Phase 2 - Activation, Preparation for Labour, Cervical ripening

Phase 3 - Stimulation, process of labour, uterine contractions, cervical dilation, foetal and placenta expulsion, delivery of conceptus, 3 stages of labour.

Phase 4 - Involution, Parturient recovery, uterine involution, cervical repair, breast feeding.

Question 9

What happens in the 3 stages of labour?

Answer 9

First stage - Contractions start, Cervix dilation. Latent phase - slow dilation of the cervix to 2-3 cm, Active phase rapid dilation of the cervix to 10cm.

Second stage - Foetus delivery, Commences at full dilation of the cervix, Maximal myometrial contractions.

Third stage - Delivery of the placenta, Expulsion of the placenta & foetal membranes, postpartum repair.

Question 10

How long is the First Delivery?

Answer 10

8-18hrs

Question 11

How long are Subsequent deliveries?

Answer 11

5-12hrs

Question 12

What is the role of the Cervix?

Answer 12

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

Question 13

What underlies softening?

Answer 13

Changes to collagen bundle structure

Question 14

What are the phases of cervical remodelling?

Answer 14

Softening – begins in first trimester
Measurable changes in compliance but retains cervical competence

Ripening – weeks and days before birth
Monocyte infiltration and IL-6 and IL-8 secretion
Hylaluron deposition

Dilation – increased elasticity
Increased hyaluronidase expression -> HA breakdown
MMPs decrease collagen content

Post-partum repair
Recovery of tissue integrity and competency

Question 15

How is timing of delivery controlled?

Answer 15

fetus determines timing of parturition through changes in fetal HPA axis
CRH levels rise exponentially towards the end of pregnancy
Decline in CRH binding protein levels, so CRH bioavailability increases

Question 16

What are CRH functions in Labour?

Answer 16

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

DHEAS - Dehydroepiandrosterone Sulphate

Question 17

What is the role of oestrogen and progesterone in Labour?

Answer 17

High progesterone through pregnancy maintains uterine relaxation

Serum estrogen:progesterone ratio may shift in favour of estrogen – this is unclear

Question 18

What are the changes in oestrogen and progesterone signalling as Labour approaches?

Answer 18

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

Question 19

What is the effect od Oestrogen and progesterone changes?

Answer 19

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 20

Where is oxytocin produced?

Answer 20

Nonapeptide (9aa) hormone synthesized mainly in the utero-placental tissues and pituitary.
Uterine oxytocin production increases sharply at onset of labour
Expression increase is driven by increase in estrogen levels.
Release promoted by stretch receptors -> Ferguson reflex

Question 21

How is Oxytocin signalled?

Answer 21

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 22

What are the functions of Oxytocin in pregnancy?

Answer 22

Increases connectivity of myocytes in myometrium (syncytium)
Destabilise membrane potentials to lower threshold for contraction
Enhances liberation of intracellular Ca2+ ion stores

Question 23

What are the prostaglandins role in Labour?

Answer 23

Primary PGs synthesized during labour are PGE2, PGF2alpha and PGI2.
Rising estrogen levels drive prostaglandin action in the uterus in two ways:
1. Rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
2. Estrogen stimulation of oxytocin receptor expression promotes PG release.

Question 24

What is the role of PGE2?

Answer 24

cervix re-modelling

Promotes leukocyte infiltration into the cervix, IL-8 release and collagen bundle re-modelling

Question 25

What is the role of PGF2-alpha?

Answer 25

myometrial contractions

Destabilises membrane potentials and promotes connectivity of myocytes (with Oxytocin)

Question 26

What is the role of PGI2?

Answer 26

myometrium

Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segnment.

Question 27

Which peptide hormones are involved in cervical remodelling?

Answer 27

Relaxin, Nitric Oxide

Question 28

How do Myometrial Contractions take place?

Answer 28

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 29

How does Foetal expulsion occur?

Answer 29

Head engages with pelvic space 34-38wks

Pressure on fetus causes chin to press against chest (flexion)
Fetus rotates (belly to mother’s spine)
Shoulders delivered sequentially (upper first) followed by torso.
expelled first after cervix dilates

Question 30

How does Placental expulsion take place?

Answer 30

Rapid shrinkage of the uterus after fetal delivery causes area of contact of placenta with endometrium to shrink
Uterine shrinkage also causes folding of fetal membranes – peel off the endometrium
Clamping of the umbilical cord after birth stops fetal blood flow to placenta -> villi collapse
Hematoma formation between decidua and placenta
Contractions expel placenta and fetal tissues

Question 31

How does Uterus repair take place?

Answer 31

Uterus remains contracted after delivery to facilitate uterine vessel thrombosis.
Uterine involution and cervix repair restore non-pregnant state
Shielding uterus from commensural bacteria
Restore endometrial cyclicity in response to hormones