Does the fetus have a microbiome? How does the placenta prevent infection? Carolyn Coyne talks about placental structure and biology, and why studying the maternal-fetal interface remains a critical area of research.

Julie's Biggest Takeaways:

The placenta forms within 3-5 days post conception as a single layer of cells surrounding the fertilized embryo. These cells differentiate and develop into more complex structures.

Very few microbes cause fetal disease. Of those that do, the disease-causing microorganisms are diverse and can lead to serious congenital defects or even death of a developing fetus. These microbes are largely grouped into the TORCH (now TORCH-Z) microorganisms:

• Toxoplasma gondii
• Other (a variety of different bacteria and viruses)
• Rubella
• Cytomegalovirus
• Herpesviruses
• Zika virus

The fetus is immunologically immature and unable to protect itself. Some of the maternal immunological molecules (such as maternal antibodies) cross the placenta to protect the fetus, but that only happens during later stages of fetal development. Between the first and second trimesters, the maternal vasculature reorganizes and maternal antibodies can begin to reach the fetus. This increases over time, until the end of the third trimester, when there is a higher concentration of maternal antibodies in fetal blood than in maternal blood.

In the later stages of development, the placenta is coated in a layer of fused cells, leading to a shared cytoplasm that covers the entire surface area of the placenta. This fused-cell layer is formed from syncytiotrophoblasts, and the fusion is facilitated by the activity of an endogenous retrovirus fusion protein.

Syncytiotrophoblasts are extremely resistant to infection with a number of different pathogens, and pathogen types. In initial tests experiments, Carolyn and her research team discovered that these cells releasing certain antimicrobial molecules to share protective properties. Syncytiotrophoblasts secrete type III interferons, which play a big role at barrier surfaces such as the airway and the gut—but unlike these barriers, the syncytiotrophoblast cells secrete type III interferons constitutively.

Links for this Episode:

• Carolyn Coyne Website on the University of Pittsburgh School of Medicine
• Arora N. et al. Microbial Vertical Transmission during Human Pregnancy. Cell Host & Microbe. May 2017.
• Coyne C.B. The Tree(s) of Life: The Human Placenta and My Journey to Learn More About It. PLoS Pathogens. April 2016.
• Ander S.E. et al. Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines. mBio. January 2018.
• Wells A.I. and Coyne C.B. Type III Interferons in Antiviral Defenses at Barrier Surfaces. Trends in Immunology. October 2018.
• Ander S.E. Diamond M.S. and Coyne C.B. Immune Responses at the Materna-Fetal Interface. Science Immunology. January 2019.
• HOM Tidbit: Women in Microbiology
• HOM Tidbit: Small Things Considered blog post: Retroviruses, the Placenta, and the Genomic Junk Drawer