Reproduction 2 - Pregnancy and Labour Flashcards
What are the three trimesters of pregnancy?
- Not defined by science, based on experience
- First (to 13 weeks, embryo to fetus), second (to 26 weeks, foetuses could survive birth here - viability) and third (to 39 weeks - term)
- If the first trimester is completed, it is likely to last until the expected delivery time
- Miscarriage is likely in the first trimester
List maternal changes in pregnancy, and the trimester they occur in
- Increased weight [3rd - not obvious a lady is pregnant in first stage]. Angle of the back changes, putting pressure on joints.
- Increased blood volume [2nd and later]
- Increased blood clotting tendency [2nd and later]
- Decreased blood pressure [2nd]
- Altered brain function [1st and later - due to high levels of steroids]
- Altered hormones [1st and later]
- Altered appetite (quantity and quality) [1st and later] GI imbalance and morning sickness, generally first trimester
- Altered fluid balance [2nd and later]
- Altered emotional state [1st and later]
- Altered joints [3rd]
- Altered immune system [1st and later]
Define conceptus
Everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)
Define embryo
The baby before it is clearly human
Define fetus
The baby for the rest of pregnancy
Define infant
Less precise, normally applied after delivery
How is pregnancy measured?
- Observations (of the mother, tissues from the foetus post miscarriage)
- Measurements of circulating factors or of dimensions
What are comparitive studies?
- Looking at embryos of different species early in development
- Can be done as they look very similar
- However, need to be cautious
- Helps to identify when the conceptus is the most vulnerable
List the key features of the placenta
- Very highly branched structure, provides a large surface area (~11m2).
- Very effective for transport of molecules between maternal and fetal circulations.
- Also anchors the placenta (and hence the baby) securely for 9 months.
- Intimate contact between maternal and placenta tissues
- Disc shaped on the fetal side, cotyledons on the maternal side (which contain one or more villi)
- Two umbilical arteries (to the placenta) carrying deoxygenated blood
- One umbilical vein (to the foetus) carrying oxygenated blood
List the functions of the placenta
- Separation (fetal and maternal vascular systems must remain separate)
- Exchange (placental villus provides a large surface for exchange to occur)
- Biosynthesis (placenta is highly active)
- Immunoregulation (preents rejection of the conceptus)
- Connection (must make strong connects with the maternal decidua and must be in contact with maternal arterial blood)
Describe the process of placental development
- Starts as a layer of single cells in the blastocyst (outer layer of the conceptus containing multinucleated syncytiotrophoblast)
- These proliferate and differentiate.
- Form a simple branched structure and then expand iteratively
- Mesenchymal cells at the centre of each villus, where the vascular system develops
- Overall structure does not change throughout pregnancy - though there are fewer cytotrophoblast present at term
What is the function of the cytotophoblast shell?
What happens to spiral arteries following its breakdown?
- Limits blood supply to the placenta and therefore embryo during early development (therefore, less likely to be damaged by oxygen free radicals - here main function of the placenta is to deliver nutrients)
- Remains until around 8 weeks post fertilisation. Block spiral arteries by cytotrophoblast plugs
- Remodelling of spiral arteries (from spiral to wide-bore vessels) and breakdown of cytotrophoblast plugs allows high volume blood supply in trimesters 2 and 3 when infant growth is greatest. Occurs from first trimester (4-6 weeks) to 16-18 weeks gestation.
List types of placental mal-development
- Miscarriage (late first trimester)
- Miscarriage (second trimester)
- Pre-eclampsia (early delivery)
- Fetal growth restriction (small infant)
How common is miscarriage?
- 350,000 per annum
- Within 13 weeks around 7,000 late miscarriages
List numbers of deliveries at term
- 37-41 weeks of gestation
- 700, 000 infants a year
- 525,000 or around 75% by labour
- 175, 000 or around 25% elective caesarean section
List number of infants deliveres preterm
- 23-37 weeks gestation
- 80, 000 infants per year
- 45000 preterm labour (difficult to stop)
- 35000 preterm emergency c-section (compromised maternal/ fetal health)
Define labour
The process of expulsion of the fetus and the placenta from the uterus.
- Fundally dominant contractions
- Fetal membrane remodeling
- Lower segment relaxation
- Cervical ripening (cervix is no longer firm) and effacement (thinning)
Describe the process of labour
- Cervical ripening and effacement (increasing)
- Co-ordinated myometrial contractions (increasing)
- Rupture of fetal membranes (lasts around 8 hours - longest in the first pregnancy)
- Delivery of infant
- Delivery of placenta (within 30 mins of the infant)
- Contraction of uterus (involution)
- Latent stage begins 8 weeks before labour, with small contractions
List the stages of labor at term
- Phase 1 lasts many hours (contractions and cervical changes)
- Phase 2 lasts hours (baby delivered)
- Phase 3 lasts 30 minutes (placenta delivery)
What causes initiation of labour at term?
- Oestrogens
- Low progesterone
- CRH
- Oxytocin
What causes initiation of labour preterm?
- Intrauterine infection
- Intrauterine bleeding
- Multiple pregnancy
- Stress (maternal)
- Others
Describe the process of cervical ripening and effacement
- Change from rigid to flexible structure
- Remodelling (loss) of extracellular matrix
- Recruitment of leukocytes (neutrophils)
- Inflammatory process (prostaglandin E2, interleukin-8)
- Local (paracrine) change in IL-8
Describe the process of co-ordinated myometrial contractions
- Fundal dominance
- Increased co-ordination of contractions
- Increased power of contractions
Describe the process of rupture of fetal membranes
- Loss of strength due to changes in amnion basement component
- Inflammatory changes, leukocyte recruitment
- Modest in normal labour, exacerbated in preterm labour
- Increased levels and activity of MMPs
- Inflammatory process in fetal membranes
What is the evidence for NFkB importance in labour?
- Almost all pro-labour genes have NFkB binding domains in their promoters, and activate NFkB
- Modification of NFkB sites in promoter sequences leads to a loss of expression in cells or in expression vectors
- Control production of cytokines (eg. IL1 beta, which in turn increases NFkB production in positive feedback)
- Important in inflammatory pathway
What is platelet activating factor?
- Part of lung surfactant
- Surfactant proteins and complexes
- Produced by maturing lung, before birth
- Levels in amniotic fluid increase near term
- Fetal signal of maturity
What regulates the inflammatory pathways in fetal membranes?
CRH (corticotrophin releasing hormone) and platelet activating factor
List things that predispose to labour
- Anything that increases CRH may predispose to labour (stress, multiple infants)
- Anything that increases muscle contraction may predispose to labour (excess stretch of uterus)
- Anything that activates inflammatory cascades may predispose to labour (eg. increased PGE2 early for labour to occur)
- The above apply to preterm labour (intrauterine infection, bleeding, twins)
Describe progesterone in human pregnancy
- Needed to sustain pregnancy
- Levels remain very high until after delivery of the placenta
- Effect lost in normal term labour
List actions of progesterone receptors
- PR-B mediates the main effects of progesterone via gene expression
- PR-A is less able to mediate these effects
- Ratio of PR-A : PR-B increases at term
- Loss or change in PR may lead to ‘functional progesterone withdrawal’
- Binds to NFkB to prevent labour occuring, prevents myometrial contractions
Describe hormone alteration in pregnancy
- HCG peaks in first trimester, and then falls (although still present later)
- Progesterone, oestrogens and human placental lactogen increase with placenta
- Progesterone highest
- High steroids suppressing HPG leading to low LH and FHS
Describe the source of progesterone during pregnancy
- Corpus luteum main source from fertilisation to 8 weeks gestation, sustained by hCG
- Placenta produces progesterone as it increases, taking over production by 10 weeks of gestation
- From 6 weeks, the corpus luteum produces less progesterone and by 9 weeks stops production
- Luteo-placental shift
Where are oestrogens from during pregnancy
- Early weeks, corpus luteum produces the oestrogens needed for pregnancy
- Later on it is produced in the fetal adrenals (developed in the first trimester), as they convert pregnenolone to androgens
- Sulphated and inactive, converted to oestradiol by the placenta
- Therefore, female fetuses are not exposed to androgens during development
Describe altered immune system in pregnancy
- Pregnancy requires the survival of a ‘non-self’ entity for a period of 9 months, with no signs of a rejection reaction in normal pregnancy.
- Decreasing Th1 responses and increasing the Th2 system. (Subtle)
- HLA-G has five known sequence variants, and it is expressed on the placenta
- The structure of HLA-G is simple compared with other HLAs. HLA-G provides an immunological signal that shows that the tissue is human – but little or no information on which human it is from. This that the maternal immune system recognises the tissue as being human, and not as being ‘non-self’
- HLA-G can suppress the activity of some leukocytes and can down-regulate the maternal immune system within the uterus.
How is pregnancy usually timed?
First day of the last menstrual period
Define embryology
The process through which a single cell (fertilised human oocyte) develops into a recognisable human being over a period of about 8 weeks.
How is the post fertilisation (PF) timing measured?
Staring from 2 weeks after last menstrual period
Describe embryo development in the foetus
- 2nd week development of bilaminar dsic
- 3rd week formation of trilaminar disc (mesoderm), CNS and somites, blood vessel initiation and formation of placental villi. (3mm).
- 4th week closure of neural tube, heart, Face, arm initiated as well as umbilical cord. Elaboration of placental villi. (4mm)
- 5th week face and limbs continue. (5-8mm)
- 6th week face, ears, hands, feet, liver, bladder, gut, pancreas. (10-14mm)
- 7th week face, ears, fingers, toes. (17-22mm)
- 8th week lungs, liver, kidneys, (28-30mm)
When are foetuses most vulnerable to teratogens?
- In the first trimester of pregnancy
- Mal devlopment allows us to determine when the foetus is the most vulnerable
What happens to spiral arteries following breakdown of the cytotrophoblast barrier?
- Remodelling of spiral arteries (from spiral to wide-bore vessels) and breakdown of cytotrophoblast plugs allows high volume blood supply in trimesters 2 and 3 when infant growth is greatest. Occurs from first trimester to 16-18 weeks gestation.
How is placental growth and development regulated?
- The placenta regulates its own growth and development through autocrine mechanisms.
- We know that it can produce a range of different growth factors and other proteins
When is term, postterm and preterm?
- Term is 37-41 weeks
- Postterm 42 weeks or more
- Preterm 22-37 weeks
List the key mediators of coordinated myometrial contractions
- Prostaglandin F2a (E2) levels increased from fetal membranes
- Oxytocin receptor increased
- Contraction associated proteins
List the key mediators of changes in the cervix during pregnancy
- Prostaglandin E2
- Interleukin-8
- Matrix metalloproteinases (MMPs)
List key mediators of rupture of the fetal membrane
- Inflammatory process in fetal membranes
- Prostaglandins, interleukins, MMPs
Why is involution of the uterus important?
- The primary process through which blood flow through the spiral arteries is stopped.
- This process is linked to increased maternal levels of oxytocin – if it does not occur spontaneously, an injection of oxytocin (or similar muscle contracting agent) can be given to accelerate the process.
- Influx of calcium is important
Describe the process of partuition (hormone basis)
- Steroidogenesis
- CRH made in the placenta.
- Stimulates prostaglandins and IL
- Can stimulate the fetus to produce cortisol, which goes back to the placenta
- However, rather than inhibiting CRH cortisol upregulates CRH production, accelerating cortisol and CRH production (positive feedback)
- Adrenal gland also produces steroids to mature the lung, which produces platelet activating factor (increases prostaglandins and IL)
- Fetal adrenal gland produces oestrogen which stimulates myometrium contractions
Describe the interaction between NFkB and progesterone in partruition
- During pregnancy large number of progesterone receptors
- Binds to NFkB to stop it working
- Progesterone will stop myometrial contractions and labour
- NFkB increase at the end of pregnancy, and progesterone receptors decrease so therefore NFkB can act to induce labour
List the maternal risks in pregnancy
- Mainly posed by labour and delivery
- Remodelling of the uterine spiral arteries can result in large blood loss hen contraction of the uterus does not occur
- Placenta must be checked to ensure that there are no pieces missing, which will permit continued blood flow through the spiral arteries
List the risks to the infant in pregnancy
- Defects in gametes (autosome chromosome addition/deletion)
- Partial chromosome loss, exchange between chromosomes, chimeras and mosaics all have variable effects on the phenotype
List the problems with the placenta during injury
- Incomplete anchorage leading to loss of pregnancy
- Detachment or issues of development
What is stillbirth?
- Death of the infant within the uterus
- Before 23 weeks it is a miscarriage, after that it is a still birth
- Can occur at any gestational age (even term)
How is stillbirth detected?
- Monitoring of fetal movements
- Ultrasound assessment of the infant
- Fetal blood flow (doppler ultrasound)
Describe PGE2 production during pregnancy
- Fetal membrane before term produces prostaglandins in higher concentrations when stimulated by IL1 beta
- However, tissues at term do not respond to IL1 beta anymore, they are already at maximum prostaglandin production
- Therefore, higher prostaglandins produced when about to go into labour (within a day or two)
How can labour be controlled?
- Platelet activating factor and CRH could be administered
- Prostaglandin administration
Describe CRH production during pregnancy
Increases around 3 weeks before pregnancy, alongside COX2 which makes the prostaglandins
What is the function of the surfactant?
Allows the lungs to fill with air when you breathe
How is labour monitored?
- Cervical ripening (becoming softer)
- Dilation (becoming stretched and thinner)
