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 Salomon; Kirsty Short; Lana McClements; Lucia de Noronha; Ruby Huang; Gabrielle T Belz; Fernando Souza-Fonseca-Guimaraes; Vicki Clifton; Arutha Kulasinghe

doi:10.1002/cti2.1488

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

Clin Transl Immunology. 2024 Feb 6;13(2):e1488. doi: 10.1002/cti2.1488. eCollection 2024.

Authors

Nataly Stylianou¹, Ismail Sebina², Nicholas Matigian³, James Monkman², Hadeel Doehler¹, Joan Röhl⁴, Mark Allenby⁵, Andy Nam⁶, Liuliu Pan⁶, Anja Rockstroh¹, Habib Sadeghirad², Kimberly Chung², Thais Sobanski¹, Ken O'Byrne⁷, Ana Clara Simoes Florido Almeida⁸, Patricia Zadorosnei Rebutini⁸, Cleber Machado-Souza⁹, Emanuele Therezinha Schueda Stonoga¹⁰, Majid E Warkiani¹¹, Carlos Salomon¹², Kirsty Short¹³, Lana McClements¹¹, Lucia de Noronha⁸, Ruby Huang¹⁴, Gabrielle T Belz², Fernando Souza-Fonseca-Guimaraes², Vicki Clifton¹⁵, Arutha Kulasinghe²

Affiliations

¹ Australian Prostate Cancer Research Centre - Queensland, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health Queensland University of Technology Brisbane QLD Australia.
² Frazer Institute, Faculty of Medicine The University of Queensland Brisbane QLD Australia.
³ QCIF Bioinformatics St Lucia QLD Australia.
⁴ Faculty of Health Sciences and Medicine Bond University Robina QLD Australia.
⁵ BioMimetic Systems Engineering Lab, School of Chemical Engineering University of Queensland (UQ) St Lucia QLD Australia.
⁶ Nanostring Technologies, Inc. Seattle WA USA.
⁷ Princess Alexandra Hospital Woolloongabba QLD Australia.
⁸ Postgraduate Program of Health Sciences, School of Medicine Pontifícia Universidade Católica do Paraná ´ -PUCPR Curitiba Brazil.
⁹ Postgraduate Program in Biotechnology Applied in Health of Children and Adolescent Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe Curitiba Brazil.
¹⁰ Department of Medical Pathology, Clinical Hospital Universidade Federal do Paraná ´ -UFPR Curitiba Brazil.
¹¹ School of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science University of Technology Sydney Sydney NSW Australia.
¹² Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine The University of Queensland Brisbane QLD Australia.
¹³ School of Chemistry and Molecular Biosciences, Faculty of Science The University of Queensland St Lucia QLD Australia.
¹⁴ School of Medicine, College of Medicine National Taiwan University Taipei Taiwan.
¹⁵ Mater Medical Research Institute University of Queensland Brisbane QLD Australia.

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.

Keywords: COVID‐19; SARS‐CoV‐2; digital spatial profiling; gene expression profiling; placental dysfunction; trophoblasts.