Lecture 13: Placenta

List three main functions of the placenta

Provides nutrients and oxygen to fetus, produces hormones Removes waste products Immune protection from maternal cells, viral and bacterial cells Buffers environment

How does the structure of the placenta lead to patchiness in terms of distribution of mosaicism?

Placenta is derived from the blastocyst in a clonal manner Some cells are from the ICM and some are from the trophoblast If early cell acquires a mutation, downstream placental structures will share that mutation and therefore affect distribution of mosaicism. Patchiness: Each cotyledon that arises from a distinct mutated cell population will be mosaic compared to other cotyledons

In what ways is the human placenta similar to mouse? In what ways is it different?

• Similarities: both are discoid, hemochorial, and trophoblast cells line maternal vessels, have analogous cells

• Differences

  • trophoblast sub-types, organization at the molecular level

  • mouse placenta has maternal blood channels arranged in parallel with fetal capillaries → maternal and fetal blood flow in

  • opposite directions for efficient counter curren exchange

  • primate placenta, maternal blood bathes the syncytiotrophoblast layer

Name two ways that the placenta evades rejection from the maternal immune cells

Immunomodulation - low expression of receptors recognized by maternal immune system, downregulation of tumour-suppressor genes

• placenta secretes immunosuppressive molecules

Physical barrier - placenta acts as barrier to maternal immune cells

In what ways is a healthy placenta similar to cancer/tumor?

Rapid proliferation, invasion of adjacent tissues Establishes its own blood supply Similar gene expression features

Tumor suppressors silenced, proto-oncogenes active Growth factors and their receptors expresse

Similar epigenomes (low DNA methylation)

High mutation rate

What are the three major types of trophoblast cells in the human placenta and what is their function?

VCT cytotrophoblast - stem cells SCT syncytiotrophpoblast - secretes hormones, nutrient transport CCC columnar cytotrophoblast - connection between mother and fetus

What cells derive from the inner cell mass?

Fibroblasts - provide structure Endothelial - fetal arteries/veins/capillaries Hofbauer cells - promote angiogenesis and innate immunity Red blood cells

In what ways does the placenta protect against SARAS-CoV-2 and some other viruses and bacteria

STB acts as barrier to viral infections

Some receptors required for viral entry are lowly expressed on STB Not expressed at all in mesenchymal or Hofbauer cells

What are some pregnancy complications that may arise from placental dysfunction?

Fetal growth restriction - small for gestational age, increase in short and long term negative health outcomes

Maternal preeclampsia - maternal hypertensive disorder

What is confined placental mosaicism? Why does it matter?

CPM - when fetus and placenta have different chromosomal makeup

Associated with increased incidence of poor growth and other adverse outcomes

• growth restriction, maternal preeclampsia, preterm delivery, increased malformations

Considering early events in development, why might CPM be more common than fetal mosaicism?

Only 3-5 cells of ICM contribute to fetus, most blastocyst cells contribute to placenta Negative selection in fetus decreases contribution of new mutation with increasing cell divisions

Give an example of how an omics tool can give insight into placental health, development or function?

Single cell transcriptomics - used to identify additional placental cell subtypes

Placental DNA circulates in maternal blood during pregnancy. What can this be useful for? What else from the placenta circulates in mother’s blood?

Non-invasive prenatal testing