Lecture 13: Placenta

What are the three main functions of the placenta?

Provides nutrients and oxygen to the fetus, produces hormones, removes waste products, and offers immune protection.

How is patchiness in distribution of mosaicism related to the structure of the placenta?

Patchiness occurs because some cells are derived from the inner cell mass (ICM) and others from the trophoblast. If an early cell acquires a mutation, it's passed on downstream to form distinct regions with mutations.

Similarities between human and mouse placenta

Both are discoid, hemochorial, and trophoblast cells line maternal vessels

Have analogous cells

Differences between human and mouse placenta

Different trophoblast sub-types and organization at the molecular level

Mouse placenta has maternal blood channels arranged in parallel with fetal capillaries, maternal and fetal blood flow in these capillaries

Opposite directions of flow for efficient counter current exchange

Primate placenta has maternal blood bathing the syncytiotrophoblast layer

The early placenta produces substances to

Rapidly proliferate and invade maternal decidua

Prevent menstruation

Avoid rejection by maternal immune system

Promote angiogenesis and establish own blood supply

What are two ways the placenta evades rejection from maternal immune cells?

Immunomodulation through low expression of receptors and secretion of immunosuppressive molecules

Physical barrier preventing maternal immune cells from accessing the placenta.

How does a healthy placenta operate similarly to cancer/tumor?

Rapid proliferation, establishment of its own blood supply, silencing of tumor suppressors, activation of proto-oncogenes, and similar epigenomes.

High mutation rate

What are the three major types of trophoblast cells in the human placenta and their functions?

VCT (cytotrophoblast) - stem cells

SCT (syncytiotrophoblast) - secretes hormones and nutrient transport

CCC (columnar cytotrophoblast) - connection between mother and fetus.

What cells derive from the inner cell mass (ICM)

Fibroblasts - provide structure

Endothelial - fetal arteries, veins, capillaries

Hofbauer cells - promote angiogenesis and innate immunity

Red blood cells

How does the placenta protect against viruses and bacteria

Syncytiotrophoblast acts as physical barrier

Low expression of receptors required for viral entry

• not expressed at all in mesenchymal/Hofbauer cells

What are some pregnancy complications that may arise from placental dysfunction

Fetal growth restriction - small for age, increase in negative health outcomes

Maternal preeclampsia - hypertensive disorder

What is confined placental mosaicism (CPM) and why is it significant?

CPM is when the fetus and placenta have different chromosomal makeups, associated with higher risks of poor growth, maternal preeclampsia, and other complications.

Why is confined placental mosaicism more common than fetal mosaicism?

Only 3-5 cells of ICM contribute to fetus, lots of blastocyst cells contribute to placenta

Stronger negative selection against mutations in fetus

What insight can single cell transcriptomics provide regarding placental health?

It helps identify additional placental cell subtypes.

GWAS studies in regards to placental health

identifies distinct and shared genetic influences between placental and fetal growth

What is a use of placental DNA circulating in maternal blood during pregnancy?

Non-invasive prenatal testing.