LECTURE 31 - implantation, placenta formation & function Flashcards

1
Q

What is a receptive endometrium?

A

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

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2
Q

What cells changes occur in the endometrium during the implantation window?

A
  • 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
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3
Q

What is implantation?

A
  • 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
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4
Q

What are the 3 stages of implantation?

A
  1. Apposition - blastocysts loosely associates with the uterine wall
  2. Attachment
  3. Invasion - blastocyst attachment to the uterine wall triggers enzyme production
    - degrades and invades the glycogen rich endometrial stroma
    - provides further nutrient support
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5
Q

What is decidualisation of the endometrium?

A

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

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6
Q

What are the 3 main types of classification of the placenta?

A
  • 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)
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7
Q

What is an invading blastocyst?

A
  • 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
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8
Q

What are the 3 main types of trophoblasts that the trophectoderm gives rise to?

A
  1. Cytotrophoblasts (villous cytotrophoblasts)
    differentiates to give –>
  2. Syncytiotrophoblast
    - forms by fusion of villous cytotrophoblasts
  3. Extravillous cytotrophpoblast
    - interstitial
    - endovascular
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9
Q

What is happening to an implanting blastocyst at ~day 15?

A
  • 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
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10
Q

What are the main stages of development of placental villi?

A
  1. Lacunae formation
  2. Primary villi
  3. Secondary villi
  4. Tertiary villi
  5. Intermediate/mature villi
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11
Q

Lacunae formation

A
  • lacunae form in the syncytiotrophoblast
  • syncytiotrophoblast invades and erodes maternal capillaries
  • these anastomose with trophoblast lacunae to form sinusoids
  • intervillous space develops
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12
Q

Primary villi

A
  • 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
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13
Q

Secondary villi

A
  • 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
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14
Q

Tertiary villi

A
  • 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)
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15
Q

Describe the structure of mature placental villi

A

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

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16
Q

Why is remodelling of the maternal blood vessels important?

A
  • 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)
17
Q

What happens to extravillous trophoblast outgrowth in the first trimester?

A
  • 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
18
Q

What maternal adaptations are there to meet increasing oxygen/ nutrient demand of the growing fetus?

A
  • 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
19
Q

How does blood flow in the placenta?

A
Umbilical arteries (deoxygenated)
--> 
fetal capillaries within villi
--> 
umbilical vein (oxygenated)
20
Q

What is transported across the placenta and how?

A
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+
21
Q

What is the placental barrier?

A

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

22
Q

What gas exchange occurs in the placenta?

A
  • 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
23
Q

How does glucose-carbohydrate metabolism occur in the placenta?

A
  • 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
24
Q

How are amino acids and urea metabolised in the placenta?

A
  • 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
25
Q

How are water and electrolytes exchanged in the placenta?

A
  • 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
26
Q

What is intra-uterine growth restriction (IUGR)?

A
  • 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