Placental Trophoblasts Express SARS-CoV-2 Entry Factors

April 14, 2021

Washington, D.C. – April 14, 2021 – While transmission of COVID-19 from mother to fetus is extremely rare, a new study has found that certain cells in the placenta contain the receptors and processing proteins necessary for COVID-19 to enter the placenta. The findings, reported in mSphere, an open-access journal of the American Society for Microbiology, suggest the mechanisms involved in the placenta’s defense against SARS-CoV-2 likely involve post-entry processing. This finding may be germane for developing new therapeutics for COVID-19.
“Trophoblasts are equipped with SARS-CoV-2 entry factors which allow the virus to enter the placenta. Since transmission of COVID-19 to the fetus is very rare, we think that the placenta engages in some type of sophisticated antiviral mechanisms to block the virus from replication in the placenta to prevent transmission to the fetus,” said lead study author Yingshi Ouyang, PhD, assistant professor in the Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women’s Research Institute, University of Pittsburgh School of Medicine.
The researchers conducted the study because prior research had suggested that the virus could not enter the placenta. In the new study, the researchers analyzed whether 4 main different types of placental cells, trophoblasts, fibroblasts, macrophages, or microvascular endothelial cells expressed the critical SARS-CoV-2 entry factors ACE2, TMPRSS2, and furin. Trophoblasts are placental cells that are present four days post-fertilization in humans; they provide nutrients to the embryo and develop into a large part of the placenta. Fibroblasts produce the structural framework for animal tissues. While macrophages are involved in the immune response, microvascular endothelial cells have an important role in vessel homeostasis.
The researchers found that all 4 types of cells expressed the protease furin, but trophoblasts also contained the receptors ACE2 and protease TMPRSS2. “We found that ACE2 and TMPRSS2 are only expressed in the trophoblasts, which are directly facing the maternal blood,” said Dr. Ouyang.
Study principal investigator Yoel Sadovsky, MD, executive director of the Magee Women’s Research Institute, and professor of obstetrics and gynecology at University of Pittsburgh School of Medicine, said they confirmed the presence of the viral entry factors in both isolated cells and tissues. “Some people thought that the placenta would not be highly infected because of the lack of those entry factors, but we found that the entry factors are there,” said Dr. Sadovsky. He said both expression analysis and functional analysis showed this to be true.
The investigators are now researching what other players or defense mechanisms are expressed in the placenta to protect the fetus. “We see distinct and marked differences between infection by SARS-CoV-2  and infection by, for example, Zika,” said Dr. Sadovsky. “We and others are investigating what is it about the placenta that it is able to resist significant infection and protects the fetus from SARS-CoV-2. Commonly, we try to study from other systems how to protect the very vulnerable placenta and fetus during pregnancy, and maybe COVID-19 provides us an opportunity to learn from the resistance of the placenta and the fetus to infection and potentially learn from this to infer to other systems.”
If the researchers can identify the factors in the placenta that are protective against SARS-CoV-2, it could lead to new therapeutics against COVID-19.


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