lecture 17: parturition

Question 1

What are words for birth?

Answer 1

• a dog whelps and gives birth to puppies
• a cow calves and gives birth to a calf
• a sow farrows and gives birth to piglets
• a ewe lambs and gives birth to lambs
• a horse foals and give birth to a foal

Question 2

What is the birth process?

Answer 2

• transition:
  
  • retain and nurture foetus
  • → expel foetus
• synchrony
  
  • parturition and foetal maturation
  • foetal and maternal regulation of timing
• activation of myometrium
• softening of cervix
• timing – synchrony with foetal maturation

Question 3

What do we mean by foetal maturation?

Answer 3

• lung
  
  • transitiin between amniotic fluid to air
  • structural maturation
  • surfactant production (cortisol induced)
• circulation
  
  • placental to pulmonary gas exchange
  • closure of foramen ovale and ductus arteriosus
• carbohyrdate and fat reserves
  
  • mobilisation of liver glycogen by cortisol
  • fat reserves released by insulin and thyroxine until lactation established

Question 4

What is the myometrium?

Answer 4

• circular and longitudinal muscle layers, blood vessels and connective tissue
• muscle cells hypertrophy during pregnancy
• electrical connection via gap junctions leading to coordinated contractions
• intracellular Ca²⁺ activates contraction
• spontaneous pacemaker activity → excitation threshold
• oxytocin

Question 5

What are hormones involved in parturition?

Answer 5

• progesterone and oestradiol
• prostaglandins
• oxytocin
• nitric oxide (NO) (vasodilation)
• relaxin

Question 6

What are progesterone and oestradiol doing in parturition?

Answer 6

• production by placenta and CL
• towards end of pregnancy usually lower P4 and higher E2
• tend to have opposing activities
• P4 tends to suppress prostaglandins in the uterus and increase Ca++ sequestration in the myometrium → tends to inhibit the pathways for uterine contraction and suppresses the production of one of the stimulators of uterine contraction
• so at birth, P4 is dropping, releasing those blocks
• at the same time E2 is rising
  
  • stimulates PG production by the uterus
  • increase number of OT receptors in the uterus i.e. myometrium is more sensitive to oxytocin
  • increases Ca2+ uptake into the cells
  • increases the gap junctions between the cells so more likely to propagate a signal
  • i.e. E2 is making the uterus more contractile

Question 7

What is the role of prostaglandins in parturition?

Answer 7

• produced in endometrium, myometrium and placenta
• PGF2a → uterine contractions
  
  • increased release of Ca2+ from intracellular stores
• PGE2 and F2a induce cervical ripening
• made from phospholipids via arachidonic acid
  
  • prostaglandin synthetase
  • unstable intermediated PGH2
  • and that through various other enzymes can be converted into PGE2, PGF2a etc
• E2 upregulates production of phospholipase A2 (converts phospholipids to arachadonic acid) while progesterone downregulates it

Question 8

What is oxytocin?

Answer 8

• produced by
  
  • hypothalamus, released from posterior pituitary
  • CL
    uterus
• induces uterine contractions
  
  • increase Ca++ influx
  • stimulate PG release
• release stimulated by cervical stimulation – Ferguson reflex
• positive feedback
• contractions → cervical stretch → oxytocin release → contractions → etc
• need pregnancy to go all the way through

Question 9

What is the role of Nitric Oxide in parturition?

Answer 9

• NO - potent inhibitor of smooth muscle contraction
• myometrium
  
  • pregnancy: progesterone promotes increased iNOS
  • shut down NO production in labour
• cervix
  
  • activation of iNOS at term
  • NO activates matrix metalloproteases (different mechanism, remodelling collagen)

Question 10

What is the role of relaxin in parturition?

Answer 10

• cytokine related to insulin
• produced in CL - released in late gestation
• softens (relaxes) connective tissue in cervix and pubic symphysis
• also can suppress uterine contractions
• stimulates mammary development

Question 11

What is the process of birth in a goat?

Answer 11

• goats rely on the corpus luteum throughout pregnancy
• cortisol is linking characteristic
• foetal pituitary
  
  • hypothalamus etc developing
  • building up endocrine system it needs to survive after it is born
  • part of that process is turning on the production of corticotrophin releasing hormone from hypothalamus which turns on ACTH
• ACTH
  
  • acts on foetal adrenal to cause release of glucocorticoids like cortisol
• foetal adrenal
  
  • also putting out C19 steroids - androgen like precursors
  • circulate
  • when they get to the placenta, aromatase can turn them into oestrogens
  • therefore a method of increasing oestrogens with maturation of foetus
• cortisol
  
  • foetal maturation
    
    • drives some of the structural maturation that needs to happen
• aromatase
  
  • activated by cortisol
• in placenta
• oestrogens in placenta
  
  • stimulate PGF2a production → luteolysis (regression of CL) therefore dropping of progesterone
• progesterone withdrawal
  
  • • PG synthesis by increased oestrogens leads to contractions of myometrium
• maternal neurohypophysis
  
  • ferguson reflex once contractions start
• myometrium

Question 12

What are placental steroidogenic enzymes activated by cortisol?

Answer 12

• cortisol activates a couple of key steps
• 17a-hydroxylase
• 17-20-lyase
• which are on the pathway between progesterone and androstenedion (C19 carbon)

Question 13

How does parturition occur in the sheep?

Answer 13

• foetal pituitary
  
  • matures
• ACTH
• foetal adrenal
  
  • increased sensitivity to ACTH at term
  • releases cortisol
• cortisol
  
  • foetal maturation
    
    • surfactant production, structural maturation of the lungs
• placenta
  
  • cortisol → 17 hydroxylase → C17 - C20 lyase → aromatase
  • aromatase converts progesterone to oestrogens i.e. still increase oestrogens at the expense of progesterone
• P4 decrease as production redirected into E2
• Progesterone withdrawal + rising oestrogens → PG synthesis → contractions in myometrium → ferguson reflex
• maternal neurohypophysis
• myometrium

Question 14

What is the process of parturition in humans?

Answer 14

• foetal pituitary
• ACTH
• foetal adrenal
  
  • produces cortisol
  • foetal maturation
  • putting out a lot of C19 steroids (largely DHAS/EA)
• placenta
  
  • no 17a-hydroxylase
  • aromatase
  • exactly what’s setting the timing is probably something different: CRF
  • C19 steroids coverted by aromatase to oestrogens
• CRF
  
  • corticotrophin releasing factor
  • in placenta
  • goes up about time for birth
  • acts on foetal adrenal
  • increases PGF2a → CL regression → prorgesterone withdrawal → PG synthesis → contractions in myometrium
  • also acts directly to increase PG synthesis
• Oestrogens → PGF2a etc
• myometrium
• maternal neurohypophysis
• progesterone withdrawal turns off iNOS
• ferguson reflex

Question 15

What are some adaptations of the foetus?

Answer 15

• foetal haemoglobin
  
  • higher affinity for oxygen than maternal haemoglobin
• bohr effect: pH change as CO2 exchanged increases O2 transfer
• note: placenta highly metabolically active – uses 30% of O2 supplied