L14: Parturition

Question 1

What are the complications of preterm labour?

Answer 1

long-term chronic lung and heart disease, diabetes, increased admission for acute illness

Question 2

What are the events of initiation of labour in sheep? what is their order?

Answer 2

• 1st event: fetal cortisol goes up
• 2nd event: maternal progesterone goes down
• 3rd event: maternal oestrogens go up
• 4th event: maternal prostaglandins go uo
• 5th event: labour

Question 3

What is the function of progesterone in pregnancy of sheep?

Answer 3

• essential for maintenance of pregnancy
• secreted firstly by CL then by placenta
• suppression of immune response
• maintains uterine quiescence / suppresses myometrial activity
• progesterone levels fall in 5+ days before labour (NOT in humans)
• progesterone receptor antagonists induce labour preterm

Question 4

What is the example of sheep with disrupted HPA axis?

Answer 4

• Because of eating a neurotoxin, lambs not producing cortisol anymore
• Cyclopian lambs

Question 5

What does cortisol stimulate?

Answer 5

cortisol stimulates 17-alpha hydroxylase expression by the trophoblast in the placenta, so progestagens can be used as the substrate for oestrogen synthesis

Question 6

What is the importance of oestrogens in pregnancy of sheep?

Answer 6

• rise 1-2 days before onset of labour
• promote uterine myometrium responsiveness
• formation of myometrium gap junctions
• formation of excitatory receptors
• stimulate secretion of prostaglanding (PG) E2 for dilatation of cervix
• stimulate secretion of myometrial stimulants (prostaglanding F2-alpha)

Question 7

What is the chronically catheterised fetal sheep experimental mode? What can be done with it?

Answer 7

A model when during pregnancy an embryo is cathetarised and put back in the womb, various signals observed.

Question 8

What is the set of events of a foetus controlling the time of its own labour?

Answer 8

1. Maturation of fetal hypothalamic-pituitary-adrenal axis
   i) In sequence CRH-ACTH-cortisol
2. Cortisol levels start and keep rising in foetus
   i) Also essential for lung development and blood pressure
3. Stimulates placental 17-alpha-hydroxylase
4. Progesterone levels fall
5. Oestrogen levels rise
6. Prostaglandin levels increase to stimulate cervix to dilate and uterus to contract – labour

Question 9

What is the importance of cortisol?

Answer 9

• stimulates maturation of the fetal lung structures and surfactant - essential to have the lung developed at deivery
• required for function of cardiovascular system and live glycogen storage
• signals the maturation of the fetus (refelcts maturation of nervous system)
• initiates labour

Question 10

What happens to myometrial activity during labour?

Answer 10

Switch myometrial activity from ‘contractures’ (low amplitude, long duration) to ‘contractions’ (high amplitude, short duration)

Question 11

How are prostaglandins important during labour in sheep?

Answer 11

• During labour PGE2 and PGF2-alpha increase locally at fetal- maternal interface (rise in amniotic fluid) and inactive metabolites increase in circulation
• PGE2 stimulates dilation of the cervix (important clinically for induction of labour)
• PG synthesis inhibitors (NSAID or COX inhibitors, e.g. asprin and indomethacin) delay/inhibit labour
• PGF2-alpha stimulates labour (mimic by infusion)

Question 12

How is collagen broken down in sheep cervix?

Answer 12

White blood cells invade and release matrix metalloproteases to break down collagen

Question 13

What are the sequential and parallel co-ordinated maturation to initiate labour?

Answer 13

• Maturation of fetus (HPA)
• Maturation of placenta (17alpha-hydroxylase)
• Excitability of myometrium (contractures: low amplitude, long duration)
• Dilation of cervix
• Stimulation of myometrium (contractions associated with active labour: high amplitude, short duration)

Question 14

How does regulation of labour happen in women?

Answer 14

• more complex
• role for fetal HPA axis, and fetal adrenal maturation for increased availability of substrates for oestrogen synthesis
• but CRH also secreted by placenta (stimulates fetal HPA?)
• no clear change in E2:P4 ratio
• gradual increase in stimulatory mediators over inhibitors
• inflammatory type response as final stimulus - initiated precociously in many deliveries preterm

Question 15

What are the knockout mouse models for parturition?

Answer 15

• Oxytocin KO – deliver on time
  i) Although pups die d1/2 due to starvation as lactation/milk let down disrupted
• PGF2alpha receptor (FP) KO – delayed delivery due to maintained progesterone by CL
• PGE2 (EP1-4) receptors individual KO – deliver on time
• COX-1 (cyclo-oxygenase for PG production) – delivered late and dead (due to extended gestation)
• COX-2 – infertile
• CRH KO – deliver on time