Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.
Journal
Clinical & translational immunology
Journal Volume
13
Journal Issue
2
Start Page
Article number e1488
ISSN
2050-0068
Date Issued
2024
Author(s)
Stylianou, Nataly
Sebina, Ismail
Matigian, Nicholas
Monkman, James
Doehler, Hadeel
Röhl, Joan
Allenby, Mark
Nam, Andy
Pan, Liuliu
Rockstroh, Anja
Sadeghirad, Habib
Chung, Kimberly
Sobanski, Thais
O'Byrne, Ken
Almeida, Ana Clara Simoes Florido
Rebutini, Patricia Zadorosnei
Machado-Souza, Cleber
Stonoga, Emanuele Therezinha Schueda
Warkiani, Majid E
Salomon, Carlos
Short, Kirsty
McClements, Lana
de Noronha, Lucia
Belz, Gabrielle T
Souza-Fonseca-Guimaraes, Fernando
Clifton, Vicki
Kulasinghe, Arutha
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.
Subjects
COVID‐19
SARS‐CoV‐2
digital spatial profiling
gene expression profiling
placental dysfunction
trophoblasts
Type
journal article