placentation & trophoblast I and II Flashcards
The placenta
- The placenta is fetal in origin at term it weighs 500-1000g
- Acts as the lungs, gut and kidneys of the fetus
- Acts as an endocrine organ releasing hormones into the maternal circulation such as hCG and progesterone
The placenta is a semi-allograft, the cells have genetic material from both the mother and the father
In a human pregnancy, fetal cells are in direct contact with maternal blood this means it comes into contact with maternal immune system so requires mechanisms to evade the maternal immune system.
However the fetal and maternal circulations do not mix
Placental development
· Blastocyst attaches and adheres to epithelial layer of uterine wall
· Trophoectoderm cells divide and migrate between epithelial cells through basement membrane and to uterine wall.
· Trophoectoderm proliferates and fuses to form a primitive syncytium (PS) beneath the implanted embryo.
· TC migrate or invade the decidua
· Lacunae (L) form by the action of proteases which later develop into the intervillous space.
· Behind the PS cytotrophoblasts proliferate and migrate through the syncytium into the uterine wall to form the anchoring villi.
implantation …
multistep process by which free floating blastocysts attaches to the endometrium , invades through epithelium and into the stroma beneath and begins to establish the placenta.
The placenta
As placenta develops , anchoring villi branch to form secondary and tertiary villi .
Blood vessels that supply foteus that supply are spiral arteries , which deliver maternal blood to the intervillious space . veins drain blood from intervillious space back into the maternal circualtion.
Highly branched with a large surface area for exchange.
Outer layer of fused cells- the syncytium
Underlying cytotrophoblast stem cells
Diffusion distance to vessels small
Growth is regulated by a number of factors including IGF I and II
Villious structure
- highly branched vascular networks of arteries and veins that take blood to and from the developing fetus.
- the vessels are very close to the surface which enables rapid exchange of material.
-Hofbauer cells are macrophages and may be involved in immune protection of placenta and regulating the formation and branching of the vessels
Formation of the syncytium
- combined action of hCG and syncytin 1/2 forms synctium
1. hCG binds to the LH/CGR receptor
2. this stimulates the production of cAMP
3. cAMP will activate membrane protein called Scramblase and PKA
4. Scramblase is responsible for the redistribution of phosphodyl serine from the inner surface of the plasma membrane to the outer surface of the membrane for apoptosis and fusion
5. PKA phosphorylates Gilial Cell Missing homologue 1 (this is a transcription factor that will move to the nucleus and regulate the expression of syncytin 1/2 and hCG.
6. Synytin 1/2 will move to the plasma membrane where it will induce self fusion and formation of primary syncytin and secondary
7. Syncytium is continually shed in to the maternal circulation and cytotrophoblast has to fuse with syncytium to replace lost material.
What is the role of synctium?
help fusion of placental cells
made in the nucleus - Gililial cell missing homologue transcription factor involved in regulating expression of synctin 1/2 in the nucleus
synctium will move to the membrane where it is involved in fusion.
what protein do you use to stain syncytium and look at it under a microscope?
- desmoplacin
- multinucleated cells
What is the function of syncytium?
Syncytin-1 is a human endogenous retroviral envelope gene product that plays an important role in the formation and maintenance of normal syncytium throughout pregnancy.
Syncytium is constantly regenerated throughout gestation and slows down towards term( to allow placental rupture in pregnancy) – to do this, cytotrophoblasts have to fuse with the syncytium to replace lost material.
Syncytium is continually being shed in to the maternal circulation and is replaced by the underlying cytotrophoblasts.
What is the role of trophoblasts in placenta formation?
trophoblasts are important causing vascular smooth muscle loss in the placental arteries to remodel them from constricted high resitence low flow vessels to low resistance high flow vessels.
Trophoblast differentiation and function
Extravillous trophoblast differentiate into endovascular and intristial trophoblasts.
Endovascular and interstitial trophoblast work together to ultimately remodel the maternal spiral arteries.
-in the initial stages of pregnancy the endovascular trrophoblast forms a trophoblast plug which prevents the maternal blood from entering the intervillus space.
-interstitial extravillous trophoblast (EVT) invades into the decidua and migrates towards spiral arteries.
What happens when the trophoblast moves into the decidua (extravillious cytotrophoblast)
as cells move into the decidua they undergo epithelial mesoncymal transition during this process the cells lose their polarity and lose adherens and as this progresses they express different cell surface markers.
What regulates growth of the trophoblast?
Growth of the trophoblast column regulated by factors such as IGF1
produced by the underlying mesenchymal cells
What factors stimulates proliferation and inhibit differentiation?
HIF-1α and Stox1
Oxygen tension and gestational age
trophoblast plug reduces level of oxygen
the villus tissue is exposed to in early gestation.
Up until 12th week the uterine spiral arteries are plugged with trophoblasts
Placental development therefore occurs under relative hypoxia 2-3% O2
While the spiral arteries are plugged nutrition is histiotrophic nutrients being secreted by the glandular cells
Following dissolution of the trophoblast plug the placenta switches to haemotrophophic nutrition
Oxygen concentration:
- 8-10 weeks gestation 2-3%
- 12-13 weeks gestation 7-8%
Why is it important to have low oxygen in early stages of pregnancy but not good to have prolonged low oxygen?
- Prolonged low oxygen leads to placental pathologies
Limitation of using animal model to study human placental development.
Animal models
There are significant differences in the placental development between mammals
Human studies are limited for ethical reasons
The similarities and difference in mice compared to humans.
- Trophoblasts invade the decidua and maternal arterial wall and come in to direct contact with maternal blood (similar)
- However there is no deep interstitial invasion of the decidua
- Mice do not exhibit the same obstetric complications as humans
Why are Apes a better animal model than mice?(bc more simialrities)
- Trophoblasts invade the decidua and maternal arterial wall and
come in to direct contact with maternal blood - Deep interstitial invasion of the decidua does occur
- Some evidence that they do exhibit the same obstetric
complications as humans - Ethically unacceptable to experiment on these animals (limitation)
more expensive and need licesnsing
If animal models arent appropriate what can we use to study placental development?
human tissue
What are two types of human tissue used?
- Trophoblast cell lines
- Tissue transfected with oncogenes
Problem with using human tissue?
Human tissue can only be obtained either in the first trimester from miscarriages or at term whereas pre eclampsia manifests in week 20 after first trimester , after birth you can observe physiological changes live while they happen
human tissue : trophoblast lines used derived from …
JEG3, Jar and BeWo
=> grow well
=> have lost some characteristics