1. Genetics and Genomics
  2. Medicine

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

  1. Roger Pique-Regi  Is a corresponding author
  2. Roberto Romero  Is a corresponding author
  3. Adi L Tarca
  4. Francesca Luca
  5. Yi Xu
  6. Adnan Alazizi
  7. Yaozhu Leng
  8. Chaur-Dong Hsu
  9. Nardhy Gomez-Lopez  Is a corresponding author
  1. Wayne State University, United States
https://doi.org/10.7554/eLife.58716
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  1. Roger Pique-Regi
  2. Roberto Romero
  3. Adi L Tarca
  4. Francesca Luca
  5. Yi Xu
  6. Adnan Alazizi
  7. Yaozhu Leng
  8. Chaur-Dong Hsu
  9. Nardhy Gomez-Lopez
(2020)
Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?
eLife 9:e58716.
https://doi.org/10.7554/eLife.58716
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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, 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.

Data availability

Placenta and decidua scRNA-seq data from first-trimester samples were downloaded through ArrayExpress (E-MTAB-6701). Data for third-trimester samples previously collected by our group are available through NIH dbGAP (accession number phs001886.v1.p1), and newly generated second-trimester scRNA-seq and third-trimester snRNA-seq data are being deposited in the same repository.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Roger Pique-Regi

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    For correspondence
    rpique@wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1262-2275

  2. Roberto Romero

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    For correspondence
    prbchiefstaff@med.wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4448-5121

  3. Adi L Tarca

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1712-7588

  4. Francesca Luca

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8252-9052

  5. Yi Xu

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Adnan Alazizi

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Yaozhu Leng

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Chaur-Dong Hsu

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Nardhy Gomez-Lopez

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    For correspondence
    ngomezlo@med.wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3406-5262

Funding

National Institutes of Health (HHSN275201300006C)

  • Roberto Romero

Wayne State University (Perinatal Initiative)

  • Adi L Tarca
  • Nardhy Gomez-Lopez

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The collection and use of human materials for research purposes were approved by the Institutional Review Board of the Wayne State University School of Medicine [IRB# 110605MP2F(RCR), IRB# 082403MP2F(5R), and IRB# 031318MP2F]. All participating women provided written informed consent prior to sample collection.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Roger Pique-Regi
  2. Roberto Romero
  3. Adi L Tarca
  4. Francesca Luca
  5. Yi Xu
  6. Adnan Alazizi
  7. Yaozhu Leng
  8. Chaur-Dong Hsu
  9. Nardhy Gomez-Lopez
(2020)
Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?
eLife 9:e58716.
https://doi.org/10.7554/eLife.58716

Share this article

https://doi.org/10.7554/eLife.58716

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Further reading

    1. Genetics and Genomics

    Single cell transcriptional signatures of the human placenta in term and preterm parturition

    Roger Pique-Regi, Roberto Romero ... Nardhy Gomez-Lopez
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    More than 135 million births occur each year; yet, the molecular underpinnings of human parturition in gestational tissues, and in particular the placenta, are still poorly understood. The placenta is a complex heterogeneous organ including cells of both maternal and fetal origin, and insults that disrupt the maternal-fetal dialogue could result in adverse pregnancy outcomes such as preterm birth. There is limited knowledge of the cell type composition and transcriptional activity of the placenta and its compartments during physiologic and pathologic parturition. To fill this knowledge gap, we used scRNA-seq to profile the placental villous tree, basal plate, and chorioamniotic membranes of women with or without labor at term and those with preterm labor. Significant differences in cell type composition and transcriptional profiles were found among placental compartments and across study groups. For the first time, two cell types were identified: 1) lymphatic endothelial decidual cells in the chorioamniotic membranes, and 2) non-proliferative interstitial cytotrophoblasts in the placental villi. Maternal macrophages from the chorioamniotic membranes displayed the largest differences in gene expression (e.g. NFKB1) in both processes of labor; yet, specific gene expression changes were also detected in preterm labor. Importantly, several placental scRNA-seq transcriptional signatures were modulated with advancing gestation in the maternal circulation, and specific immune cell type signatures were increased with labor at term (NK-cell and activated T-cell signatures) and with preterm labor (macrophage, monocyte, and activated T-cell signatures). Herein, we provide a catalogue of cell types and transcriptional profiles in the human placenta, shedding light on the molecular underpinnings and non-invasive prediction of the physiologic and pathologic parturition.

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    Determining the effects of paternal obesity on sperm chromatin at histone H3 lysine 4 tri-methylation in relation to the placental transcriptome and cellular composition

    Anne-Sophie Pepin, Patrycja A Jazwiec ... Sarah Kimmins
    Research Article Updated

    Paternal obesity has been implicated in adult-onset metabolic disease in offspring. However, the molecular mechanisms driving these paternal effects and the developmental processes involved remain poorly understood. One underexplored possibility is the role of paternally induced effects on placenta development and function. To address this, we investigated paternal high-fat diet-induced obesity in relation to sperm histone H3 lysine 4 tri-methylation signatures, the placenta transcriptome, and cellular composition. C57BL6/J male mice were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. Males were timed-mated with control-fed C57BL6/J females to generate pregnancies, followed by collection of sperm, and placentas at embryonic day (E)14.5. Chromatin immunoprecipitation targeting histone H3 lysine 4 tri-methylation (H3K4me3) followed by sequencing (ChIP-seq) was performed on sperm to define obesity-associated changes in enrichment. Paternal obesity corresponded with altered sperm H3K4me3 at promoters of genes involved in metabolism and development. Notably, altered sperm H3K4me3 was also localized at placental enhancers. Bulk RNA-sequencing on placentas revealed paternal obesity-associated sex-specific changes in expression of genes involved in hypoxic processes such as angiogenesis, nutrient transport, and imprinted genes, with a subset of de-regulated genes showing changes in H3K4me3 in sperm at corresponding promoters. Paternal obesity was also linked to impaired placenta development; specifically, a deconvolution analysis revealed altered trophoblast cell lineage specification. These findings implicate paternal obesity effects on placenta development and function as one potential developmental route to offspring metabolic disease.