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Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes

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, a...

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Autores principales: Monti, Paola, Solazzo, Giulia, Accurti, Veronica, Gambitta, Bianca, Iodice, Simona, Boito, Simona, Cantone, Laura, Manenti, Alessandro, Dioni, Laura, Montomoli, Emanuele, Persico, Nicola, Bollati, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252646/
https://www.ncbi.nlm.nih.gov/pubmed/37298229
http://dx.doi.org/10.3390/ijms24119278
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author Monti, Paola
Solazzo, Giulia
Accurti, Veronica
Gambitta, Bianca
Iodice, Simona
Boito, Simona
Cantone, Laura
Manenti, Alessandro
Dioni, Laura
Montomoli, Emanuele
Persico, Nicola
Bollati, Valentina
author_facet Monti, Paola
Solazzo, Giulia
Accurti, Veronica
Gambitta, Bianca
Iodice, Simona
Boito, Simona
Cantone, Laura
Manenti, Alessandro
Dioni, Laura
Montomoli, Emanuele
Persico, Nicola
Bollati, Valentina
author_sort Monti, Paola
collection PubMed
description 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 11–13 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.
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spelling pubmed-102526462023-06-10 Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes Monti, Paola Solazzo, Giulia Accurti, Veronica Gambitta, Bianca Iodice, Simona Boito, Simona Cantone, Laura Manenti, Alessandro Dioni, Laura Montomoli, Emanuele Persico, Nicola Bollati, Valentina Int J Mol Sci Article 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 11–13 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. MDPI 2023-05-25 /pmc/articles/PMC10252646/ /pubmed/37298229 http://dx.doi.org/10.3390/ijms24119278 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Monti, Paola
Solazzo, Giulia
Accurti, Veronica
Gambitta, Bianca
Iodice, Simona
Boito, Simona
Cantone, Laura
Manenti, Alessandro
Dioni, Laura
Montomoli, Emanuele
Persico, Nicola
Bollati, Valentina
Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title_full Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title_fullStr Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title_full_unstemmed Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title_short Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
title_sort pyroptosis: a promising mechanism linking sars-cov-2 infection to adverse pregnancy outcomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252646/
https://www.ncbi.nlm.nih.gov/pubmed/37298229
http://dx.doi.org/10.3390/ijms24119278
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