{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:29:47Z","timestamp":1787801387044,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2014\u201cRicerca Corrente\u201d IRCCS"},{"name":"Public Health Sciences PhD Fellowship, University of Milan, Italy"},{"name":"Environmental Sciences PhD Fellowship, University of Milan, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11\u201313 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and\/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.<\/jats:p>","DOI":"10.3390\/ijms24119278","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T02:05:44Z","timestamp":1685066744000},"page":"9278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-497X","authenticated-orcid":false,"given":"Paola","family":"Monti","sequence":"first","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-7507","authenticated-orcid":false,"given":"Giulia","family":"Solazzo","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Accurti","sequence":"additional","affiliation":[{"name":"Fetal Medicine and Surgery Service, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Gambitta","sequence":"additional","affiliation":[{"name":"Fetal Medicine and Surgery Service, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-8761","authenticated-orcid":false,"given":"Simona","family":"Iodice","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Boito","sequence":"additional","affiliation":[{"name":"Fetal Medicine and Surgery Service, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3660-129X","authenticated-orcid":false,"given":"Laura","family":"Cantone","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Manenti","sequence":"additional","affiliation":[{"name":"VisMederi Srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dioni","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7595-4974","authenticated-orcid":false,"given":"Emanuele","family":"Montomoli","sequence":"additional","affiliation":[{"name":"VisMederi Srl, 53100 Siena, Italy"},{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Persico","sequence":"additional","affiliation":[{"name":"Fetal Medicine and Surgery Service, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"CRC, Center for Environmental Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-9598","authenticated-orcid":false,"given":"Valentina","family":"Bollati","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"CRC, Center for Environmental Health, University of Milan, 20122 Milan, Italy"},{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1749-6632.2010.05938.x","article-title":"Inflammation and pregnancy: The role of the immune system at the implantation site","volume":"1221","author":"Mor","year":"2011","journal-title":"Ann. 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