Researchers from the Institut Pasteur, the CNRS, Inserm, Necker-Enfants Malades Hospital (AP-HP), and Université de Paris have identified a novel cellular mechanism that alters placental development, potentially causing serious complications during pregnancy. The mechanism is linked with the production of interferon, a molecule produced particularly in response to viral infection.
The scientists demonstrated that interferon may be responsible for placental abnormality by preventing syncytiotrophoblast formation.
Syncytiotrophoblast is the external layer of the placenta, and is composed of cells that fuse together, forming giant cells that are optimised for the placenta’s barrier and exchange functions.
Interferon specifically induces the production of a family of cellular proteins known as IFITMs (interferon-induced transmembrane proteins), which block the cell fusion activity of syncytin. Failure in proper formation of syncytiotrophoblast thus can cause placental insufficiency and hinder foetal development. An abnormal syncytiotrophoblast can be observed in conditions such as slow intrauterine growth, lupus, and in women whose foetus has Down syndrome.
IFITM proteins are beneficial since they prevent viral fusion with cellular membrane, thereby stopping viruses from entering and multiplying within cells. The scientists used experimental models and human cells to demonstrate that this beneficial effect can nevertheless be harmful if IFITM proteins are produced in an important level in the placenta.
Interferon is a substance produced by immune cells during infection to combat viruses and other intracellular microbes. High levels of interferon are also observed in autoimmune or inflammatory diseases such as lupus, and also in some infections.
“Identifying the role of IFITMs gives us a better understanding of the mechanisms involved in placental development and how it may be disrupted during infections and other diseases,” comments Olivier Schwartz, head of the Virus and Immunity Unit at the Institut Pasteur in a statement.
High-risk pregnancies occur frequently, and have multiple causes. It is estimated that 10% to 20% of pregnant women miscarry during their first trimester of pregnancy. Slow foetal growth may also arise as a result of maternal infection with certain microbes, parasites, or viruses (such as toxoplasmosis or infection with rubella virus, cytomegalovirus, herpes, or Zika) or because of genetic or autoimmune diseases.