lecture 17: parturition Flashcards Preview

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Flashcards in lecture 17: parturition Deck (15):
1

What are words for birth?

  • 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 

2

What is the birth process?

  • 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 

3

What do we mean by foetal maturation?

  • 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 

4

What is the myometrium?

  • 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 

5

What are hormones involved in parturition?

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

6

What are progesterone and oestradiol doing in parturition?

  • 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 

7

What is the role of prostaglandins in parturition?

  • 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 

8

What is oxytocin?

  • 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 

9

What is the role of Nitric Oxide in parturition?

  • 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)

10

What is the role of relaxin in parturition?

  • 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 

11

What is the process of birth in a goat?

  • 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 

12

What are placental steroidogenic enzymes activated by cortisol?

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

13

How does parturition occur in the sheep?

  • 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 

14

What is the process of parturition in humans?

  • 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 

15

What are some adaptations of the foetus?

  • 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