LECTURE 31 - implantation, placenta formation & function Flashcards
What is a receptive endometrium?
To enable place for blastocyst to implant
Mid-luteal phase
- secretory activity peaks - endometrial cells rich in glycogen and lipids ~14mm thick
- glands increase in number and size
- maintained by high levels of progesterone and oestrogen levels
- endometrial receptivity is marked by changes on surface epithelium
What cells changes occur in the endometrium during the implantation window?
- between day 19/20-23-24 of period
- ciliated epithelial cells to help blastocyst oocyte to be transported
- microvillus present that also change
- pinopode formation occurs
- uprising of surface of epithelial cell
- microvilli reduce in size and surface swells in size
- blastocyst hidden by structure
- important for adhesion of blastocysts on surface
- important for implantation
What is implantation?
- embryo attachment and penetration of the endometrium and maternal circulatory system to form the placenta
- conceptus enters the uterus bathed in uterine secretion for 1-3 days prior to hatching from the zona pellucida
What are the 3 stages of implantation?
- Apposition - blastocysts loosely associates with the uterine wall
- Attachment
- Invasion - blastocyst attachment to the uterine wall triggers enzyme production
- degrades and invades the glycogen rich endometrial stroma
- provides further nutrient support
What is decidualisation of the endometrium?
Where the blastocysts attach there is
- oedema
- changes in ECM (extracellular matrix)
- angiogenesis
- leucocyte infiltration
- uterine natural killer cells (uNK cells)
Also have packing tissue (stroll fibroblasts) that have a dramatic change in phenotype, they undergo morphological and biochemical changes
fibroblast-like –> polygonal
- become nutrient rich, store glycogen and lipids and are ready to support implanting blastocyst by producing lots of proteins e.g. prolactin, IGFBP-1
The decidua completely surrounds the implanted blastocyst by day ~10
What are the 3 main types of classification of the placenta?
- based on structural organisation and separation of metal and maternal blood supplies
1. Haemochorial - the chorion is in direct contact with the blood (humans)
2. Endotheliochorial - the maternal blood vessel endothelium comes in direct contact with the chorion (dog, cat)
3. Epithelialchorial - the most primitive form - the maternal epithelium of the uterus comes into contact with the chorion (cows, pigs)
What is an invading blastocyst?
- blastocyst comes in and starts to differentiate
- driven by gradients of growth factors particularly oxygen tension
- inner cell mass is forming embryo
- trophectoderm around outs the contributes to placenta differentiates itself and produces lots of enzymes and hCG
What are the 3 main types of trophoblasts that the trophectoderm gives rise to?
- Cytotrophoblasts (villous cytotrophoblasts)
differentiates to give –> - Syncytiotrophoblast
- forms by fusion of villous cytotrophoblasts - Extravillous cytotrophpoblast
- interstitial
- endovascular
What is happening to an implanting blastocyst at ~day 15?
- sat on top of decidualised endometrium completely enclosed
- growing and developing
- O2 and nutrients reach the developing embryo by diffusion from the surrounding decidua
- the initial phases of development occur at low O2 tensions (no firm blood supply)
- this whole phase is called the Histiotrophic phase
What are the main stages of development of placental villi?
- Lacunae formation
- Primary villi
- Secondary villi
- Tertiary villi
- Intermediate/mature villi
Lacunae formation
- lacunae form in the syncytiotrophoblast
- syncytiotrophoblast invades and erodes maternal capillaries
- these anastomose with trophoblast lacunae to form sinusoids
- intervillous space develops
Primary villi
- day 11-13: trophoblasts invade into decidua
- swellings of cytotrophoblasts extended into syncytiotrophoblast layer form finger-like projections in the decidua
- cover the entire surface of the blastocyst
Secondary villi
- extra-embryonic mesoderm (mesoblast) invades the core of the primary villous (>day 16)
- mesoderm covers the entire surface of the chorionic sac
- villi continue to extend into the decidua between the blood filled lacunae
Tertiary villi
- mesodermal cells differentiate to form endothelial and other cell types
- blood vessels form an aterio-capillary network in the villi
- these vessels fuse with developing vessels in the stalk - to link the fetal blood system via invading vessels from the umbilical cord (end week 3)
Describe the structure of mature placental villi
Stem villi - basal part of villi, attached to chorionic plate
Branch/intermediate villi - project from the sides of stem villi
Terminal villi - swellings at the tips of branch villi contain terminal vessels - form convoluted knots where the majority of exchange takes place (continue to be produced throughout gestation)
- the cytotrophoblast layer becomes very thin, but remains mostly in tact ~80% coverage in full term placenta
Why is remodelling of the maternal blood vessels important?
- critical to establish a low resistance - high flow blood supply to intervillous space
- essential for normal pregnancy
Spiral arteries
- resistance vessels supplying the endometrium/decidua
- coiled appearance in the inner myometrium and decidua
- ~150 arteries are transformed
- diameter is increased 10-fold (200μm to ~2mm)
What happens to extravillous trophoblast outgrowth in the first trimester?
- cytotrophoblast columns form at the tips of anchoring villi
- extravillous trophoblasts (EVT) differentiate and form interstitial and endovascular EVT
- EVT invade the decidua and occlude the spiral arteries
- replace the endothelium and smooth muscle cells forming the endovascular trophoblast layer
- establish normal utero-placental dynamics
What maternal adaptations are there to meet increasing oxygen/ nutrient demand of the growing fetus?
- uterine blood flow increases ~20 fold during pregnancy via uterine (+ ovarian) arteries
- cardiac output increases by 30-40% (>25% of cardiac output goes to the placenta)
- increased maternal blood volume ~40%
- increased ventilation rate
How does blood flow in the placenta?
Umbilical arteries (deoxygenated) --> fetal capillaries within villi --> umbilical vein (oxygenated)
What is transported across the placenta and how?
There is a parabiotic relationship between mother and fetus Diffusion - O2 and CO2 - Na+ - urea - fatty acids and sugars
Active transport
- amino acids
- iron
- Ca2+
What is the placental barrier?
Haemotrophic nutrition (> week 14) - maternal blood delivers nutrients to fetal circulation across the placenta
~3-4 layers separate the maternal and fetal circulations
1. syncytiotrophoblasts
2. cytotrophoblasts
3. connective tissue
4. fetal capillary endothelium
What gas exchange occurs in the placenta?
- O2 and CO2 by passive diffusion
- ~40% more haemoglobin in fetal vs adult
- fetal haemoglobin ~80% in late gestation
- higher affinity for O2 achieves saturation at lower pO2
- simultaneous movement of CO2 on a concentration gradient back to mother
- double Bohr effect results in increase of pH on fetal side - promotes O2 uptake at lower pO2
How does glucose-carbohydrate metabolism occur in the placenta?
- uptake by insulin insensitive hexose transporters (GLUT3, GLUT1)
- maternal insulin regulates glucose - increases glycogen and adipose stores
- maternal tissues show insulin insensitivity/ resistance (due to human placental lactogen) promoting transfer of blood glucose to the placenta
- glucose is also metabolised to lactate which is used as an energy source by the fetus
How are amino acids and urea metabolised in the placenta?
- fetus regulates maternal amino acid metabolism through progesterone
- mother retains extra amino acids and transports them to fetal circulation
- some are metabolised e.g. serine –> glycine
- fetal urea diffuses passively into the maternal blood
How are water and electrolytes exchanged in the placenta?
- exchange in water occurs in placenta and non-placental chorion at the amnion
- amniotic fluid increases from 15ml at 8weeks to 450ml at week 20
- net production decreased to 0 by week 34
- Na+ and other electrolytes transfer readily across the placenta
What is intra-uterine growth restriction (IUGR)?
- occurs in 8-14% of normal pregnancies, associated with pregnancy hypertension
- blood flow on both sides of placenta compromised
- O2 passes across by simple diffusion - reduced flow leads to fetal hypoxia
- glucose transfer is generally not affected
- reduced fatty acid transfer
Amino acid transport is compromised - reduced ion transport
- acidosis
- reduced bone mineralization in 3rd trimester
