Week 9 Flashcards
(20 cards)
What is the role of the placenta?
- Exchange (gases, nutrients, waste) between mother and foetus
- Hormone production - an endocrine organ
- Immunological barrier/interface between mother and foetus
- Metabolic function
- Haematopoetic function in early pregnancy
What are the components of the placental villi?
Thick walled vessels
Stem villus
Mature intermediate villi
Very thin walled vessels
Terminal villi
What are the steps of villus and vessel growth?
a. Weeks 5-6
Vasculogenesis
b. Weeks 7-9
c. Weeks 9-25
Prevalence of branching angiogenesis in pre-existing and newly developing villi
d. Weeks 20-32
Pre-existing villi;
Capillary regression, media formation, newly developing villi; switch to non-branching angiogenesis
e. Weeks 25-40
Normal development: prevalence of non-branching angiogenesis
What is vasculogenesis?
The development of vessels from mesenchymal precursors (differentiation of angioblasts into endothelial cells and subsequent morphogenesis)
What is angiogenesis?
The development of new vessels from pre-existing vessels (continues the growth of the vasculature - sprouting and splitting
What are the stages of villous vessel maturation?
Development and recruitment of haemangioblastic progenitor cells
Formation of haemangioblastic cords
Endothelial tube formation
Stimulation of non-branching angiogenesis
Establishment and maintenance of vessel walls
What key factors regulating vasculogenesis/angiogenesis?
VEGFA
Angiopoietin 1 and 2
What is the biology of VEGFA?
Di-sulfide linked homodimer. At least 5 splic variants
- VEGF206
- VEGF189
- VEGF165
- VEGF145
- VEGF121
Longer forms are strongly heparin binding, but can be proteolitically cleaved to release bio-active molecules
VEGF-A, the prototypical member of a gene family, VEGF-A, -B, -C, -D, PIGF (And VEGF-E and VEGF-Fs)
Why is VEGFA regulation important?
Too little is lethal
Too much is harmful
Regulated by:
- Oxygen
- Hormones (e.g. oestradiol and progesterone)
What is the endothelial response to VEGFA?
Phosphorylation of receptors and MAP kinase, PLC and Act
Increased vascular permeability
Profileration
Migration
Induction of protease and protease inhibitors
Endothelial maintenance (survival) factor
When is the onset of maternal blood flow in the placenta?
Spiral artery remodelling
What are trophoblast plugs?
Early placentation occurs in a low oxygen environment
<20mmHg at 7-10 weeks gestation
This rises to >50mmHg at 11-14 weeks gestation
This coincides with the onset of maternal blood flow in the inter villous space as the plugs in the spiral arterioles are displaced
What do NK cells play a role in?
Vascular remodelling
What are the spiral artery remodelling cellular interactions?
Decidual natural killer cell
- Regulate EVT invasion
- Prime vessel for remodelling
- Induce VSMC disorganisation/loss
Decidual macrophage
- Regulate EVT invasion
- Accumulate around spiral arteries
- Phagocytose dead cells
Extravillous trophoblast
- Invade interstitially/endovascularly
- Plug spiral arteries
- Remodel extracellular matrix
- Induce EC and VSMC apoptosis
Fibrinoid
- Deposited by EVT
Extracellular matrix
Endothelial cell
- Interact with EVT
- Temporarily lost from vessel
VSMC
- Lost from vessel
- De-differentiate/migrate
- Undergo apoptosis
- Loss of vessel contractility
What are the consequences of perturbed blood flow in the placenta?
High velocity flow (1-2ms-1 vs 10cms-1)
- Damages anchoring and floating villi
- Increased trophoblast deportation3
Decreased transit time
Turbulent flow
- Less effective gas transfer
What do we know about stress in pre-eclampsia?
Pretty familiar with placental stress
- Oxidative
- Immunological
- Endoplasmic reticulum
What are some molecular factors associated with pre-eclampsia?
Placental growth factor (PIGF) and soluble fms-like tyrosine kinase 1 (sFLT1) - angiogenic factors
What is the mechanism of action of sFLT1?
Potential disruption of VEGFA and PIGF signalling
Antiangiogenic action/state
What happens to VEGF binding in preeclampsia?
Endothelial dysfunction
Impaired relaxation
Loss of VEGF binding
What is VEGF instrumental for?
Endothelial cell proliferation
