Parturition Flashcards
Outline the hormonal changes that occur around parturition
- Drop in progesterone, increase in oestradiol
- Increase in foetal cortisol
- Increase in prolactin
How does cortisol affect the oestrogen:progesterone ratio?
- Rise in foetal cortisol increases oestrogen:progesterone ratio
- Upregulates aromatase enzymes
- Convert androgens to oestrogens
- Reduces progesterone production
What are the potential endocrine reasons for delayed parturition?
- Too much progesterone
- Too little oestradiol preventing increased oxytocin
- Decreased glucocorticoids
What is the dominant hormone during pregnancy?
Progesteron
What is the major hormonal change that occurs prior to parurition?
Switch from progesterone to oestrogen
What happens to foetal cortisol approaching parturition?
Cortisol increases (is the stimulus for parturition)
What initiates parturition?
Foetal cortisol levels
What causes the increase in foetal cortisol?
- Increased stress of foetus
- In response to reachign maximal size within available space and reaching maximal nutritional demands
How does foetal cortisol cause changes that will ultimately lead to parturition?
- alters catalytic enzymes
- Progesterone converted to oestradiol using series of enzymes, upregulated by foetal cortisol
- Also stimulates productin of surfactant in lungs
What are some functions of glucocorticoids?
- Affect glucose metabolism (inhibit insulin)
- Anti-inflammatory and immuno-suppressive
- Negative feedback to hypothalamus and ant. pit in HPA axis
- Increases uterine secretions
- Stimulates uterine prostaglandin production
What changes allow myometrial contractions to take place?
- Increase in foetal cortisol
- Decrease in progesterone to remove block
What may cause prolonged gestation?
- Lack of HPA axis
- Inability to produce foetal cortisol
- e.g. ingestion of “skunk cabbage” producing cyclopic lamb with absence of hypophysial stalk and pituitary, and adrenal hypoplasia
Explain the importance of uterine prostaglandin production prior to parturition
- Stimulated by foetal cortisol
- Causes uterine contraction
- Acts on ovary and causes lysis of CL to further reduce progesterone levels
- Stimulates relaxin production
What is the role of relaxin in parturition?
Increases elasticity of cervix for parturition
What stimulates oxytocin release during parturition?
- Pressure from the foetus on the cervix
- Controlled by neurohormonal reflex
Describe the neurohormonal reflex in oxytocin release
- Increasing pressure on cervix stimulates pressure sensitive neurons
- Relay afferent info to PVN of hypothalamus
- Neural input to posterior pituitary = oxytocin release
- Induces further contractions, increases pressure, positive feedback loop
Outline the use of glucocorticoids for induction of parturition
- Induce abortion/parturition in late term gestation
- Support final developmental stages of young in humans (surfactant)
- Mimic action of foetal cortisol
Outline the use of oxytocin in the induction of parturition
- Given to strengthen contractions and expel placenta/membranes
- e.g. uterine inertia, removal of uterine produced, retained placenta
Outline the use of PGF2a in the induction of parturition
- Causes luteolysis
- Strengthens contractions
- Give prior to/during delivery
Outline the use of beta-adrenergic agonists in parturition
- Inhibits contractions and causes relaxation
- Given to reduce contractions e.g. in C-section, or to correct dystocia
Outline the actions of the mediators of contraction
- Stretch increases COX-2 and oxytocin receptors
- Oxytocin binds to receptors to simulate contraction (positive feeback) and also increases arachidonic acid
- Arachidonic acid converted by COX-2 to PGE and PGF2a
- PGs potentiate oxytocin
- Oestradiol increases COX-2 and oxytocin receptors
Describe the biochemical mechanisms in myometrial contraction
- Hormone (oxytocin) binds to membrane receptor
- Second messenger signalling
- Calcium into cytoplasm from SER or extracellular sources
- Calcium binds to calmodulin forming complex
- Complex interacts with MLCK, needed for myosin activation (phosphorylates myosin)
- Myosin binds to actin, walks up to generate pull
- Contraction in all planes due to fibres running in multiple
directions - No troponin complex for regulating contraction
Describe the physical contraction mechanism in myometrium
- 3D as fibres run in different directions
- Actin fibres attach to cell wall and dense bodies in cytoplasm
- When activated, slide over myosin bundles causing shortenin go f cell walles
- No striations
- Myosin performs powestroke
Describe the role of gap junctions in the coordination of contractility
- Low resistance pathways allowing action as functional syncitium
- Allow passage of small molecules
- Increase in number and size towards parturition
- Oestradiol stimulates their production
- Presence and permeability under steroid and PG control
- Some influence of stretch
Describe the structure of gap junctions in the myometrial myocytes
- Made up of connexons and connexins, half in each cell
- Each connexon is made up of 6 connexins
What is the role of progesterone in myometrial activity?
Inhibits it
What is the role of oxytocin in myometrial activity?
- Stimulates cascade of events leading to contraction
- Increases force, duration and frequency of contractions
What is the role of oestradiol in myometrial activity?
- Stimulates production of gap junctions
- Makes contractions more likely
- Allows synchornous contraction
What is the role of prostaglandins in myometrial activity?
- Isoform locally produced to act locally
- PGF2a = contraction
- PGI2 = relaxation
- PGE2 = cervical softening
What is the neural input into myometrial activity?
- Autonomic via pelvix plexus innervates uterus through alpha1 and 2 and beta 1 and 2 adrenergic receptors
- Alpha-1 activation causes contraction
- Beta-2 activation causes relaxation
- High progesterone increases number of beta receptors
What are the stages of parturition?
- INitiation of myometrial contractions
- Expulsion of the foetus
- Expulsion of the foetal membranes
Describe the first stage of parturition
- Onset of uterine contractions
- Foetus produces cortisol, upregulation of enzymes
- P4 to E2
- Removal of P4 block on contractions
- Increased E2 increases repro tract secreions
- Cortisol increases uterine PGs
- PG causes relaxin prod
- Degradation of collagen and remodelling of cervical matrix over period of hours to days
- Cervical os opens
- PG lyses CL if present
- Uterine contraction increases due to increase in PGF2a and E2
- Foetus assumes disposition for expulsion
Outline the onset of coordinated myometrial contractions
- Transition from uncoordinate to regular peristaltic type
- Duration, frequency and amplitude increase
- Peristaltic waves towards vulva
Describe assumption of foetal disposition for parturition in general
- Adoopts characteristic position for passage through cervix to vagina then vulva
- Some species variation
- Trigger for foetal response unknown *may be result of increasing uterine pressure
Describe assumption of foetal disposition in foal and pup
- Rotation from ventral to dorsal position
- Forelimbs, head and neck extend
Describe assumption of foetal disposition in calf and lamb
Simple extension of limbs and head
Describe the reduction in attachment of placenta in teh first stage of parturition
- Uterine contractions cause less intimate attachment
- Superficial cells undergo fatty degeneration
- in species with deciduate placenta, separation of margins and haemorrhage begins
Give the signs of the first stage of parturition
- Uterine/myometrial contractions
- Anorexia, shivering
- Nesting behaviour
- Vulval discharge
Compare the second stage of parturition in monotocous and polytocous species
- Monotocous: one foetus to be delivered, expulsion of foetus
- Polytocous: multiple foetuses to be delivered, cannot spearate second and third stage
Describe the second stage of parturition
- Expulsion of foetus
- Onset of abdominal contractions
- Ferguson’s reflex initiated
- Allantochorion ruptures as consequence of movements towards teh cervix
- Contractions continue, amnion at vulva
- Foetal limbs in amnion
- Foetus hypoxic in birth canal
- Foetal head at vulva, maximal contractile effort
- Complete when all foetuses delivered