Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 14:9:e58716.
doi: 10.7554/eLife.58716.

Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

Roger Pique-Regi  1   2   3 , Roberto Romero  1   2   4   5   6   7 , Adi L Tarca  1   3   8 , Francesca Luca  2   3 , Yi Xu  1   3 , Adnan Alazizi  2 , Yaozhu Leng  1   3 , Chaur-Dong Hsu  1   3   9 , Nardhy Gomez-Lopez  1   3   10
Affiliations

Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

Roger Pique-Regi et al. Elife. .

Abstract

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 exists. The novel coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. Herein, building upon our previous single-cell study (Pique-Regi et al., 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy in the placenta as well as in third-trimester chorioamniotic membranes. We report that co-transcription of ACE2 and TMPRSS2 is negligible in the placenta, thus not a likely path of vertical transmission for SARS-CoV-2. By contrast, receptors for Zika virus and cytomegalovirus, which cause congenital infections, are highly expressed by placental cell types. These data show that the placenta minimally expresses the canonical cell-entry mediators for SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; genetics; genomics; human; human biology; medicine; placenta; pregnancy vertical transmisssion; scRNA-seq; viral receptors.

PubMed Disclaimer

Conflict of interest statement

RP, RR, AT, FL, YX, AA, YL, CH, NG No competing interests declared

Figures

Figure 1.
Figure 1.. Transcriptional map of the human placenta, including the decidua, in the three trimesters of pregnancy.
(A) Uniform Manifold Approximation Plot (UMAP), where dots represent single cells/nuclei and are colored by cell type (abbreviations used are: STB, Syncytiotrophoblast; EVT, Extravillous trophoblast; CTB, cytotrophoblast; HSC, hematopoietic stem cell; npiCTB, non-proliferative interstitial cytotrophoblast; LED, lymphoid endothelial decidual cell) (B) UMAP plot with cells/nuclei co-expressing one or more transcripts for ACE2 and TMPRSS2, genes that are necessary for SARS-CoV-2 viral infection and spreading, in red.
Figure 1—figure supplement 1.
Figure 1—figure supplement 1.. UMAP highlighting cells expressing syncytiotrophoblast genes CGA + CSH1 + GH2 that are more efficiently captured when isolating nuclei in snRNA-seq.
Uniform Manifold Approximation Plot (UMAP), where dots represent single cells/nuclei and are colored the combined gene expression of CGA + CSH1 + GH2 and normalized to transcripts per million per cell.
Figure 2.
Figure 2.. Dot plot depicting the expression of different viral receptors/molecules used by SARS-CoV-2, CMV, and ZIKV.
Each row represents a different cell type, and columns are grouped first by virus type, receptor/molecule gene, and placental tissue/time-of sampling (1DP, 2DP and 3DP represent the first, second, and third trimester, 3Nuc represents the third trimester nuclei, and 3CAM represents the third trimester chorioamniotic membranes). The size of the dot represents the proportion of cells that express the receptor with more than zero transcripts, and the color represents the average gene expression for the subset of cells expressing that gene in transcripts per million (TPM). Cell type abbreviations used are: STB, Syncytiotrophoblast; EVT, Extravillous trophoblast; CTB, cytotrophoblast; HSC, hematopoietic stem cell; npiCTB, non-proliferative interstitial cytotrophoblast; LED, lymphoid endothelial decidual cell.
Figure 2—figure supplement 1.
Figure 2—figure supplement 1.. Gene expression values for BSG across tissues collected by the GTEx project.
For each tissue, a violin plot and a boxplot describe the variation in gene expression levels for BSG across all of the samples collected by the project sorted left to right by median gene expression (plot generated through the GTEx portal).
Figure 2—figure supplement 2.
Figure 2—figure supplement 2.. Dot plot depicting the expression of different viral receptors/molecules used by virus that caused congenital infection.
Each row represents a different cell type, and columns are grouped first by virus type, receptor/molecule gene, and placental tissue/time-of sampling (1DP, 2DP and 3DP represent the first, second and third trimester, 3Nuc represents the third trimester nuclei, and 3CAM represents the third trimester chorioamniotic membranes). The size of the dot represents the proportion of cells that express the receptor with more than zero transcripts, and the color represents the average gene expression for the subset of cells expressing that gene in transcripts per million (TPM). Cell type abbreviations used are: STB, Syncytiotrophoblast; EVT, Extravillous trophoblast; CTB, cytotrophoblast; HSC, hematopoietic stem cell; npiCTB, non-proliferative interstitial cytotrophoblast; LED, lymphoid endothelial decidual cell.
See this image and copyright information in PMC

References

    1. Aagaard KM, Lahon A, Suter MA, Arya RP, Seferovic MD, Vogt MB, Hu M, Stossi F, Mancini MA, Harris RA, Kahr M, Eppes C, Rac M, Belfort MA, Park CS, Lacorazza D, Rico-Hesse R. Primary human placental trophoblasts are permissive for zika virus (ZIKV) Replication. Scientific Reports. 2017;7:41389. doi: 10.1038/srep41389. - DOI - PMC - PubMed
    1. Adams Waldorf KM, Stencel-Baerenwald JE, Kapur RP, Studholme C, Boldenow E, Vornhagen J, Baldessari A, Dighe MK, Thiel J, Merillat S, Armistead B, Tisoncik-Go J, Green RR, Davis MA, Dewey EC, Fairgrieve MR, Gatenby JC, Richards T, Garden GA, Diamond MS, Juul SE, Grant RF, Kuller L, Shaw DW, Ogle J, Gough GM, Lee W, English C, Hevner RF, Dobyns WB, Gale M, Rajagopal L. Fetal brain lesions after subcutaneous inoculation of zika virus in a pregnant nonhuman primate. Nature Medicine. 2016;22:1256–1259. doi: 10.1038/nm.4193. - DOI - PMC - PubMed
    1. Adams Waldorf KM, Nelson BR, Stencel-Baerenwald JE, Studholme C, Kapur RP, Armistead B, Walker CL, Merillat S, Vornhagen J, Tisoncik-Go J, Baldessari A, Coleman M, Dighe MK, Shaw DWW, Roby JA, Santana-Ufret V, Boldenow E, Li J, Gao X, Davis MA, Swanstrom JA, Jensen K, Widman DG, Baric RS, Medwid JT, Hanley KA, Ogle J, Gough GM, Lee W, English C, Durning WM, Thiel J, Gatenby C, Dewey EC, Fairgrieve MR, Hodge RD, Grant RF, Kuller L, Dobyns WB, Hevner RF, Gale M, Rajagopal L. Congenital zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nature Medicine. 2018;24:368–374. doi: 10.1038/nm.4485. - DOI - PMC - PubMed
    1. Al-Haddad BJS, Oler E, Armistead B, Elsayed NA, Weinberger DR, Bernier R, Burd I, Kapur R, Jacobsson B, Wang C, Mysorekar I, Rajagopal L, Adams Waldorf KM. The fetal origins of mental illness. American Journal of Obstetrics and Gynecology. 2019;221:549–562. doi: 10.1016/j.ajog.2019.06.013. - DOI - PMC - PubMed
    1. Aldo P, You Y, Szigeti K, Horvath TL, Lindenbach B, Mor G. HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells. American Journal of Reproductive Immunology. 2016;76:348–357. doi: 10.1111/aji.12578. - DOI - PubMed

Publication types

MeSH terms

Associated data