{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:55:56Z","timestamp":1792803356577,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["Estatal de I + D + I 2020\u20132027"],"award-info":[{"award-number":["Estatal de I + D + I 2020\u20132027"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Instituto de Salud Carlos III","award":["P2022\/BMD-7321"],"award-info":[{"award-number":["P2022\/BMD-7321"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Development Regional Fund \u201cA way to achieve Europe\u201d","award":["Estatal de I + D + I 2020\u20132027"],"award-info":[{"award-number":["Estatal de I + D + I 2020\u20132027"]}]},{"name":"European Development Regional Fund \u201cA way to achieve Europe\u201d","award":["P2022\/BMD-7321"],"award-info":[{"award-number":["P2022\/BMD-7321"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe3+) was observed in placenta samples stained with Perls\u2019 Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.<\/jats:p>","DOI":"10.3390\/antiox13050591","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-1708","authenticated-orcid":false,"given":"Miguel A.","family":"Ortega","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Garcia-Puente","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-6397","authenticated-orcid":false,"given":"Oscar","family":"Fraile-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Pekarek","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cielo","family":"Garc\u00eda-Montero","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-2476","authenticated-orcid":false,"given":"Julia","family":"Bujan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonel","family":"Pekarek","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvestra","family":"Barrena-Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Center for Cognitive and Computational Neuroscience, Complutense University of Madrid, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Gragera","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-3004","authenticated-orcid":false,"given":"Inmaculada 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melchor","family":"\u00c1lvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Prince of Asturias, Networking Research Center on for Liver and Digestive Diseases (CIBEREHD), 28806 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-6198","authenticated-orcid":false,"given":"Natalio","family":"Garc\u00eda-Honduvilla","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 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