13. Parturition Flashcards
What controls the labour timing and process in sheep?
Sequential + parallel signalling - fetal signal to mother -> labour initiation
What are the complications of preterm birth?
Preterm birth:
- low birthweight
- Survival 85% - important neonatal care
- High morbidity - having a disease / symptom of disease
- Long-term chronic lung, heart disease, diabetes
What are the main components of labour initiation in sheep?
- Fetal cortisol - signals for initation of labour
- Maternal progesterone - falls - pregnancy no longer supported
- Maternal oestrogens - induce prostaglandin production
- Maternal prostaglandins - cervix dialates
Explain the role of progesterone role in labour in sheep
Progesterone - maintains pregnancy:
- secreted first by CL - placenta takes over
- suppresses immune response to fetus
- maintains uterine quiescence - no contractions
-> progesterone levels fall 5 days before labour - progesterone receptor antagonists can be used to induce labour
How are the cortisol levels raised by the fetus?
Fetal anterior pituitary secretes adenocorticotropic hormone (ACTH) - drives cortisol levels up -> signals to maternal tissue for labour + for final maturation of fetal organs
Why are congenital disorders associated with delayed labour?
In congenitally defected sheep - non-functional fetal hypothalamic pituitary adrenal axis (HPA) - no cortisol - no signal to mother for labour initiation
What maternal structure recognises raised cortisol levels?
Placenta - recognises cortisol spike - 17 alpha hydroxylase activated -> induces oestrogen production
Fetal and placental sterodogenesis - cortisol
Explain the role of oestrogens in sheep labour
Oestrogens - induce **prostaglandin secretion **- cervix dialation:
- rise 1-2 days before labour
- promotes myometrium of uterus responsiveness - formation of gap junctions + excitatory receptors
- elevated oestrogens stimulate prostaglandin (PG) E2 secretion for cervix dialation + activates myometrium stimulants
Does the fetus or the mother control the timing of labour in sheep?
The fetus controls labour timing:
- maturation of fetal HPA axis - secretes ACTH -> cortisol signal to mother -> stiulates placental 17 alpha hydroxylase -> progesterone levels fall -> osetrogen levels rise -> prostaglanding levels rise to stimulate cervix dialation + uterus contractions
What is the experimental model for investigating sheep fetal initiation of labour?
Experimental model -** chronically catheterised fetal sheep**
Can experiment with:
- removing HPA axis components
- block hypothalamo - pituitary link
- measure circulating hormones
- replace removed factors to control labour induction
- stimulate labour by adding fetal HPA back
Why is cortisol crucial for fetal maturation and is the trigger for birth?
Cortisol - needed for fetal maturation because:
- stimulates fetal lung maturation and surfactant secretion
- need for cardiovascular function and liver glycogen storage
- reflects maturation of nervous system
- initiates labour in maternal tissues
What is the maternal response to fetal cortisol signal for labour?
Maternal response to cortisol:
- dilate cervix
- switch from myometrial contractures -> contractions in uterus
Explain the role of prostaglandins in labour in sheep
Prostaglandings (PG) - PGE2 and PGF2alpha increase locally at fetal-maternal interface:
- PGE2 stimulates dilation of cervix
- PG synthesis inhibitors delay / inhibit labour
- PGF2alpha stimulates labour
How is cervix tissue remodelled in labour in sheep?
Just before / during labour cervix tissue undergoes collage breakdown:
- WBCs recruited to cervix - neutrophils in humans / eosinophils in sheep - contain granules with collagen proteases - digest collagen - better delivery - remodel back after labour
What is the labour timing regulation in women?
What is a difference between sheep and women in response to cortisol?
In women fetal cortisol doesn’t activate 17alpha hydroxylase in placenta - expressed by fetus
What model should be used to study human parturition?
Human parturition not fully studied - models used - sheep + mice - but different mechanisms - not very representative - KO in mice
What are the differences betwene the models used to study human parturition and human mechanism of labour induction?
Different mechanisms controlling labour initiation
