Molecular mechanisms of labour Flashcards
Placental clock concept
Increased placenta CRH at term –> stim fetal pit to release ACTH –> increase fetal adrenal DHEA (oest precursor) secretion –> increase MGJ –> uterine contraction
Flaw in PCC?
Anencephalic babies still deliver spont
Message from baby?
Seen in mice
Fetal surfactant act amn macro which migrate to uterine wall and act inflam g.e. –> labour
What happens during labour?
Cervix remodelled Pro-inflam needed Myocyte depol and increase IC ca Increased MGJ Change in myo responsiveness to prog
Myometrial pro-quiescent mol
Prog, GaS, CRH, cAMP, PGE2, PKC, PKA, cGMP, NO
Myometrial contractile-ass mol
Oest, CRH, Gaq, oxytocin, PGE2, PGF2a, Calcium, IP3
3 stages of parturition
- Cervical dilation
- Fetal expulsion
- Placental delivery
What helps myometrial contractility?
Inflam
Differential g.e.
Elevated IC calcium (volt-gate calcium and IC stores from SR)
Nifedipine
Ca channel blocker
Inhib prem myo contraction
Oxytocin
Increase IC ca by releasing IC stores
Increase OTR on fundal myo
Released by cervical stim and myo stretch
Secreted from paravent nuc - postive FB
OT and IC Ca
OTR activation –> IP3 act –> IP3R on SR –> Act Ca channels on SR –> IC Ca increase
PGF2a does same via FPR
Atosiban
OTR antag, prevents premat contract via OTR
Carboprost
Blocks PGF2a action
PPH
Myometrial quiescence
Sig binds R in myo Increase 2nd messenger mol Act enzymes that phos cell pt Dephos of myosin light-chain kinase Promoted by progesterone (stops MGJ, induces cAMP and impairs OT and PGF2a
Antag of quies
- oest - gap junc and OTR
- CRH - general inflam
- PGs
- Calcium ions
- Generalised inflam