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However, the mechanisms underpinning SARS\u2010CoV\u20102\u2010induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS\u2010CoV\u20102 infection.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We utilised whole\u2010transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS\u2010CoV\u20102 in the third trimester of their pregnancy (\n n<\/jats:italic>\n \u2009=\u20097) and those collected prior to the start of the coronavirus disease 2019 (COVID\u201019) pandemic (\n n<\/jats:italic>\n \u2009=\u20099).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS\u2010CoV\u20102 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with\u00a0vasodilation (\n NOS3<\/jats:italic>\n ), oxidative stress (\n GDF15<\/jats:italic>\n ,\n CRH<\/jats:italic>\n ) and preeclampsia (\n FLT1<\/jats:italic>\n ,\n EGFR<\/jats:italic>\n ,\n KISS1<\/jats:italic>\n ,\n PAPPA2<\/jats:italic>\n ) were enriched with SARS\u2010CoV\u20102. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS\u2010CoV\u20102 samples compared to uninfected controls.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS\u2010CoV\u20102 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\u2010CoV\u20102 infection.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cti2.1488","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T04:15:09Z","timestamp":1707279309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Whole transcriptome profiling of placental pathobiology in SARS\u2010CoV\u20102 pregnancies identifies placental dysfunction signatures"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8006-5730","authenticated-orcid":false,"given":"Nataly","family":"Stylianou","sequence":"first","affiliation":[{"name":"Australian Prostate Cancer Research Centre \u2013 Queensland, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health Queensland University of Technology Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3232-3472","authenticated-orcid":false,"given":"Ismail","family":"Sebina","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Medicine The University of Queensland Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7735-9415","authenticated-orcid":false,"given":"Nicholas","family":"Matigian","sequence":"additional","affiliation":[{"name":"QCIF Bioinformatics St Lucia QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-8402","authenticated-orcid":false,"given":"James","family":"Monkman","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Medicine The University of Queensland Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Doehler","sequence":"additional","affiliation":[{"name":"Australian Prostate Cancer Research Centre \u2013 Queensland, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health Queensland University of Technology Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-8730","authenticated-orcid":false,"given":"Joan","family":"R\u00f6hl","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences and Medicine Bond University Robina QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0423-4560","authenticated-orcid":false,"given":"Mark","family":"Allenby","sequence":"additional","affiliation":[{"name":"BioMimetic Systems Engineering Lab, School of Chemical Engineering University of Queensland (UQ) St Lucia QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-2245","authenticated-orcid":false,"given":"Andy","family":"Nam","sequence":"additional","affiliation":[{"name":"Nanostring Technologies, Inc. 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