Whole transcriptome profiling of placental pathobiology in SARS‐CoV‐2 pregnancies identifies placental dysfunction signatures

Nataly Stylianou, Ismail Sebina, Nicholas Matigian, James Monkman, Hadeel Doehler, Joan Röhl, Mark Allenby, Andy Nam, Liuliu Pan, Anja Rockstroh, Habib Sadeghirad, Kimberly Chung, Thais Sobanski, Ken O'Byrne, Ana Clara Simoes Florido Almeida, Patricia Zadorosnei Rebutini, Cleber Machado‐Souza, Emanuele Therezinha Schueda Stonoga, Majid E Warkiani, Carlos SalomonKirsty Short, Lana McClements, Lucia de Noronha, Ruby Huang, Gabrielle T Belz, Fernando Souza‐Fonseca‐Guimaraes, Vicki Clifton, Arutha Kulasinghe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ‘preeclampsia-like syndrome’. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection.

Methods
We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9).

Results
Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls.

Conclusions
Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
Original languageEnglish
Article numbere1488
Pages (from-to)1-11
Number of pages11
JournalClinical & Translational Immunology
Volume13
Issue number2
DOIs
Publication statusPublished - 6 Feb 2024

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