156639 20251030145435.0 doi 10.1016/j.placenta.2025.02.018 sideral 143905 ART-2025-143905 eng Medel-Martinez, Ana The placental transcriptomic profile determined by maternal COVID-19 disease encompasses alterations reminiscent of preeclampsia 2025 Access copy available to the general public Unrestricted Introduction. During initial stages of the pandemic, SARS-CoV-2 infection during pregnancy was related to adverse pregnancy outcomes and alterations in the placenta. Whether placental abnormalities in pregnant women with COVID-19 still persist afterwards remains poorly studied. Here, we determined whether the absence of obstetric complications after maternal COVID-19 disease, including preeclampsia, is accompanied by a complete return to normalcy in terms of placental physiology. Methods. Placental RNA was purified from placental samples from SARS-CoV-2 positive mothers taken either in 2022, when Omicron was the predominant variant of concern (termed Omicron) (n = 21); or from healthy pregnancies predating the pandemic (termed preCOVID-19). Our cohort included samples from pregnant women who got infected weeks and even months before term. We performed RNA-seq, identified differentially expressed genes and examined to which biological, biochemical and cellular pathways they belong, using gene set enrichment analysis. Results. We identified 71 differentially expressed genes (DEGs) (defined by p-value ≤0.05 and fold change (FC) of ≤ -2 or ≥2). The alterations identified in placentas delivered by mothers who suffered an episode of COVID-19 disease could be mainly attributed to pathways related to organogenesis, extracellular matrix organization and oxygen transport. These alterations were also detected after exclusion of gestational diabetes mellitus (GDM) samples. Although none of the samples were taken from cases of preeclampsia, several of the relevant DEGs have been previously reported as dysregulated in hypertensive disorders of pregnancy including preeclampsia. Discussion. We propose that maternal SARS-CoV-2 infection causes alterations in gene expression that are indicative of vascular defects in the placenta info:eu-repo/grantAgreement/ES/DGA/B46-20R info:eu-repo/grantAgreement/ES/DGA/B46-23R info:eu-repo/grantAgreement/ES/DGA/LMP228_21 info:eu-repo/grantAgreement/ES/ISCIII-FEDER/CM21-00045 nfo:eu-repo/grantAgreement/ES/ISCIII/FI21-00224 info:eu-repo/grantAgreement/ES/ISCIII/INT20-00033 info:eu-repo/grantAgreement/ES/ISCIII/JR19-00006 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/submittedVersion Strunk, Mark Cebollada-Solanas, Alberto (orcid)0000-0002-3312-7759 Puente-Santamaría, Laura Gómez-Muñoz, Sonia Universidad de Zaragoza Fabre, Marta Universidad de Zaragoza Paules, Cristina Universidad de Zaragoza (orcid)0000-0001-6795-0367 Oros, Daniel Universidad de Zaragoza (orcid)0000-0002-8476-9161 Schoorlemmer, Jon 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1013 645 Universidad de Zaragoza Dpto. Cirugía Área Obstetricia y Ginecología 1012 X Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Técnica. Lab. y Talleres 165 (2025), 127-135 Placenta PLACENTA 0143-4004 1064003 http://zaguan.unizar.es/record/156639/files/texto_completo.pdf Preprint 1530088 http://zaguan.unizar.es/record/156639/files/texto_completo.jpg?subformat=icon icon Preprint oai:zaguan.unizar.es:156639 articulos driver 2025-10-30-14:52:16 ARTICLE