Labour and Parturition Flashcards
What holds pregnancy inside uterus?
cervix
What changes occur in the cervix during labour and birth?
The cervix is usually tight and closed during pregnancy and birth it needs to open to allow the expulsion of contents of the uterine cavity
During the 9 months of pregnancy the cervix acts as the stopper between the inside and outside. How is the cervix prompted to change for pregnancy?
By a phenomenon called uterine quiescence (where the muscles of the uterus remains not active or contracting it is stretching and growing)
How is uterine quiescence controlled?
by progesterone
How does progesterone function?
inhibits NFkB and COX-2 pathway which controls the myometrial contractility and reduced the inflammatory process
What is the role of progesterone during pregnancy
minimise myometrial contractions
promotes a firm and closed cervix
- helps keep pregnancy in uterus and prevents accidental expulsion
What are the factors that initiate labour?
- progesterone withdrawal
- extracellular matrix remodelling
- inflammatory mediators
- prostaglandins
- surfactant protein A
- corticotropin releasing hormone (CRH)
How does the withdrawal of progesterone help initiate labour?
progesterone helps keeps cervix long and closed during pregnancy and inhibits the myometrium from contracting in mice and rats
In humans does progesterone withdrawal help with initiating labour?
no circulating progesterone levels are unchanged during labour
Why does progesterone withdrawal not initiate labour in humans?
humans have a slightly different progesterone receptor.
Progesterone in humans can be bound to progesterone receptor A or B or a hetero-dimer whereas rats and mice only have one progesterone receptor
The targets for gene expression in the 3 human progesterone receptors are all different
Progesterone receptor expression is altered in labour in humans. What are the different levels of progesterone during different points of labour?
in preterm labour (pregnancy and not ready to go into labour)
- low expression of progesterone receptor A and B
in labour
- up-regulation of receptor A
What is the relationship between progesterone receptors and labour in humans?
the up regulation of receptor A is what plays an important role in the initiation of labour
With the increased expression of progesterone receptor A there is also an increase in what kind of gene expression?
the genes expressed by receptor A are pro-inflammatory which leads to the up-regulation of pro-inflammatory markers and cytokines
this with-drawls the effects of progesterone on reducing inflammation
*note that progesterone itself is inflammatory
With the up-regulation of progesterone receptor A there is a simultaneous withdrawal of progesterone. Why is this?
There is a down regulation of the things that enhance progesterone activity:
- cAMP response element binding protein (CBP) and steroid receptor co-activators (SRC) are significantly reduced
Why is CBP and SRC significantly reduced when there is a functional progesterone withdrawal?
these molecules enhance the activity of progesterone (helping it suppress our inflam responses)
How do we know that inflammation plays an important role in the initiation of labour?
as progesterone receptor A is up-regulated during labour it produces more inflammatory molecules and simultaneously withdrawing the effects that progesterone has on reducing inflammation (too much to keep up with).
What is the function of the cytotrophoblast in inflammation?
manage and monitor the pro-inflammatory pathways stimulated by the withdrawal of progesterone function and stimulation of progesterone receptor A response genes
Why is corticotrophin releasing hormone (CRH) known as the clock of the placenta?
it is a protein released by the placenta that seems to play a role in initiating the onset of labour
As you get closer to labour CRH levels increase significantly
- CRH binding protein (CRH BP) is high throughout pregnancy preventing CRH from being used until labour when it decreases significantly when CRH increases
CRH levels increase corresponding with labour. What occurs in CRH levels in pre-term labour
CRH levels are higher in pre-term labour than term labour
In spontaneous pre-term labour mother the CRH levels were high throughout the whole pregnancy rather than a normal term pregnancy.
- CRH levels in pre-term labour mother rise exponentially the closer they got to delivery
What are the trends seen in term and post term labours with CRH levels?
term labour
- have relatively low CRH until the 3rd trimester
post term
- lower levels of CRH than term mothers that very slowly rose as they went into the third trimester
CRH is produced by the placenta and plays a role in fetal and maternal circulation. What suppresses CRH?
progesterone and nitric oxide
The presence of CRH promotes the production of what hormone?
estrogens
and the effect of estrogen dependant hormones
The presence of CRH accumulates in the placental circulation. What is the effects of this on maternal hormone pathways?
stimulates ACTH which then increases cortisol and DHEAS
cortisol and DHEAS simultaneously promote the production for more CRH
The presence of CRH accumulates in the placental circulation. What is the effects of this on fetal hormone pathways?
fetal brain will also respond by releasing ACTH and releasing cortisol
ACTH also increases surfactant protein A (lines the lungs and allows for fetus to transition from a water envrio to air enviro)
Cortisol also promotes production of DHEAS which also produces more CRH from placenta
Levels of CRH are increased due to maternal and fetal stress hormones. Increases in CRH help the placenta with
getting ready for delivery and labour