{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:50:14Z","timestamp":1785163814371,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Intrauterine fetal death and perinatal death represent one of the most relevant medical scientific problems since, in many cases, even after extensive investigation, the causes remain unknown. The considerable increase in medical legal litigation in the obstetrical field that has witnessed in recent years, especially in cases of stillborn births, has simultaneously involved the figure of the forensic pathologist in scientific research aimed at clarifying the pathophysiological processes underlying stillbirth. Methods: our study aims to analyze cases of sudden intrauterine unexplained death syndrome (SIUD) to evaluate the role of oxidative stress in the complex pathogenetic process of stillbirth. In particular, the immunohistochemical expression of specific oxidative stress markers (NOX2, NT, iNOS, 8-HODG, IL-6) was evaluated in tissue samples of placentas of SIUDs belonging to the extensive case series (20 cases), collected from autopsy cases of the University of Ferrara and Politecnica delle Marche between 2017 and 2023. Results: The study demonstrated the involvement of oxidative stress in intrauterine fetal deaths in the placenta of the cases examined. In SIUD, the most expressed oxidative stress markers were NOX2 and 8-HODG. Conclusions: The study contributes to investigating the role of oxidative stress in modulating different pathways in unexplained intrauterine fetal death (SIUD) tissues.<\/jats:p>","DOI":"10.3390\/cells13161347","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T13:35:49Z","timestamp":1723556149000},"page":"1347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sudden Intrauterine Unexplained Death (SIUD) and Oxidative Stress: Placental Immunohistochemical Markers"],"prefix":"10.3390","volume":"13","author":[{"given":"Angelo","family":"Montana","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, University Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-5525","authenticated-orcid":false,"given":"Letizia","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Legal Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Legal Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantaleo","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Obstetrics and Gynecology, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-1202","authenticated-orcid":false,"given":"Cristina","family":"Taliento","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Obstetrics and Gynecology, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Fulcheri","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology, Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16148 Genoa, Italy"},{"name":"Fetal-Perinatal Pathology Unit, IRCCS-Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasio","family":"Tini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, University Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-2651","authenticated-orcid":false,"given":"Francesca","family":"Buffelli","sequence":"additional","affiliation":[{"name":"Fetal-Perinatal Pathology Unit, IRCCS-Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-1669","authenticated-orcid":false,"given":"Margherita","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Legal Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/jmf.16.2.43.45","article-title":"Autoptic Examination in Sudden Infant Death Syndrome and Sudden Intrauterine Unexpected Death: Proposal of a National Law","volume":"16","author":"Matturri","year":"2004","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_2","first-page":"5","article-title":"Proposal of the Acronym \u201cSIUDS\u201d for Unexplained Stillbirths, Like \u201cSIDS\u201d","volume":"3","author":"Lavezzi","year":"2014","journal-title":"J. Neonatal Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ottaviani, G. (2016). Defining Sudden Infant Death and Sudden Intrauterine Unexpected Death Syndromes with Regard to Anatomo-Pathological Examination. Front. Pediatr., 4.","DOI":"10.3389\/fped.2016.00103"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ottaviani, G. (2014). Crib Death-Sudden Infant Death Syndrome (SIDS): Sudden Infant and Perinatal Unexplained Death: The Pathologist\u2019s Viewpoint, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-08347-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13052-018-0594-6","article-title":"Inequalities in Infant Mortality in Italy","volume":"45","author":"Simeoni","year":"2019","journal-title":"Ital. J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F118","DOI":"10.1136\/fn.87.2.F118","article-title":"Comparative Epidemiology of Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death","volume":"87","author":"Arnestad","year":"2002","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Grzeszczak, K., \u0141anocha-Arendarczyk, N., Malinowski, W., Zi\u0119tek, P., and Kosik-Bogacka, D. (2023). Oxidative Stress in Pregnancy. Biomolecules, 13.","DOI":"10.20944\/preprints202310.1578.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s13760-020-01308-3","article-title":"Pathophysiology of Hypoxic-Ischemic Encephalopathy: A Review of the Past and a View on the Future","volume":"120","author":"Greco","year":"2020","journal-title":"Acta Neurol. Belg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","article-title":"Superoxide Dismutase. An Enzymic Function for Erythrocuprein (Hemocuprein)","volume":"244","author":"McCord","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.12.009","article-title":"Free Radicals, Metals and Antioxidants in Oxidative Stress-Induced Cancer","volume":"160","author":"Valko","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2174\/1389200023337054","article-title":"The Cytochrome P450 Superfamily: Biochemistry, Evolution and Drug Metabolism in Humans","volume":"3","author":"Danielson","year":"2002","journal-title":"Curr. Drug Metab."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fuchs, J. (1992). Oxidative Injury in Dermatopathology, Springer.","DOI":"10.1007\/978-3-642-76823-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1007\/BF01504715","article-title":"\u00dcber Die Katalyse Des Hydroperoxydes","volume":"20","author":"Haber","year":"1932","journal-title":"Naturwissenschaften"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bbamcr.2006.05.003","article-title":"Activation of Superoxide Dismutases: Putting the Metal to the Pedal","volume":"1763","author":"Culotta","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.pharmtox.45.120403.095857","article-title":"Glutathione Transferases","volume":"45","author":"Hayes","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0367-326X(00)00164-7","article-title":"Effect of Feronia Limonia on Mosquito Larvae","volume":"71","author":"Rahuman","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6501046","DOI":"10.1155\/2017\/6501046","article-title":"Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans","volume":"2017","author":"Marrocco","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/1471-0528.17727","article-title":"Ambient Air Pollution and Adverse Birth Outcomes: A Review of Underlying Mechanisms","volume":"131","author":"Fussell","year":"2024","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.placenta.2016.04.001","article-title":"Mitochondrial\u2013Endoplasmic Reticulum Interactions in the Trophoblast: Stress and Senescence","volume":"52","author":"Burton","year":"2017","journal-title":"Placenta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.placenta.2017.01.116","article-title":"The Role of Cellular Senescence in Ageing of the Placenta","volume":"52","author":"Cox","year":"2017","journal-title":"Placenta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.placenta.2015.12.018","article-title":"Reduced Placental Oxygenation during Subclinical Uterine Contractions as Assessed by BOLD MRI","volume":"39","author":"Sinding","year":"2016","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1161\/01.RES.0000024411.22110.AA","article-title":"Hypoxia-Reoxygenation: A Potent Inducer of Apoptotic Changes in the Human Placenta and Possible Etiological Factor in Preeclampsia","volume":"90","author":"Hung","year":"2002","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ncb1909","article-title":"Persistent DNA Damage Signalling Triggers Senescence-Associated Inflammatory Cytokine Secretion","volume":"11","author":"Rodier","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Baldari, B., De Simone, S., Cipolloni, L., Frisoni, P., Alfieri, L., D\u2019Errico, S., Fineschi, V., Turillazzi, E., Greco, P., and Vitagliano, A. (2023). Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512221"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Schiavone, S., Neri, M., Trabace, L., and Turillazzi, E. (2017). The NADPH Oxidase NOX2 Mediates Loss of Parvalbumin Interneurons in Traumatic Brain Injury: Human Autoptic Immunohistochemical Evidence. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09202-4"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Schiavone, S., Neri, M., Maffione, A.B., Frisoni, P., Morgese, M.G., Trabace, L., and Turillazzi, E. (2019). Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051242"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bpobgyn.2010.10.016","article-title":"Oxidative Stress","volume":"25","author":"Burton","year":"2011","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Grossini, E., Aquino, C.I., Venkatesan, S., Tro\u00eca, L., Tizzoni, E., Fumagalli, F., Ferrante, D., Vaschetto, R., Remorgida, V., and Surico, D. (2024). Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202403.1238.v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mito.2017.09.001","article-title":"Mitochondrial DNA Content: A New Biomarker for Sudden Intrauterine Unexplained Death Syndrome (SIUDS)","volume":"40","author":"Lattuada","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0140-6736(15)00837-5","article-title":"Stillbirths: Rates, Risk Factors, and Acceleration towards 2030","volume":"387","author":"Lawn","year":"2016","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0140-6736(15)00954-X","article-title":"Stillbirths: Ending Preventable Deaths by 2030","volume":"387","author":"Kinney","year":"2016","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1515\/jpm-2015-0318","article-title":"Classification of Stillbirths Is an Ongoing Dilemma","volume":"44","author":"Nappi","year":"2016","journal-title":"J. Perinat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0143-4004(98)80019-2","article-title":"Evidence for Oxygen-Derived Free Radical Mediated Damage to First Trimester Human Trophoblast in Vitro","volume":"19","author":"Watson","year":"1998","journal-title":"Placenta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.3109\/14767058.2015.1046045","article-title":"Placental Telomere Shortening in Stillbirth: A Sign of Premature Senescence?","volume":"29","author":"Ferrari","year":"2016","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0002-9440(10)61778-6","article-title":"In Vitro Ischemia-Reperfusion Injury in Term Human Placenta as a Model for Oxidative Stress in Pathological Pregnancies","volume":"159","author":"Hung","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0002-9440(10)64733-5","article-title":"Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia","volume":"156","author":"Many","year":"2000","journal-title":"Am. J. Pathol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/16\/1347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:36:11Z","timestamp":1760110571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/16\/1347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":36,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["cells13161347"],"URL":"https:\/\/doi.org\/10.3390\/cells13161347","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]}}}