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Neutrophil extracellular traps in the pathogenesis of placenta-associated pregnancy complications: molecular mechanisms, biomarkers, and therapeutic perspectives

Year: 2026
Type: article
Abstract: Introduction . Placenta-associated pregnancy complications (preeclampsia, fetal growth restriction, preterm birth, recurrent pregnancy loss, antiphospholipid syndrome, gestational diabetes mellitus) share impaired placentation and endothelial dysfunction. Neutrophil extracellular traps (NETs) act as key drivers of sterile inflammation and microthrombosis at the maternal–fetal interface. Aim : to summarize current evidence on NETosis molecular pathways, their pathogenic involvement across placenta-associated complications as well as translational potential of circulating biomarkers and targeted therapies. Materials and Methods . A narrative review using structured search strategies in PubMed/MEDLINE, Scopus, eLibrary, and CyberLeninka (2004–2026) was conducted. Eighty peer-reviewed publications (80 % in English) were included based on predefined eligibility criteria. Results . Both suicidal and vital NETosis pathways are characterized. Physiological NETs formation occurs during early gestation, whereas excessive NETosis coupled with impaired endogenous DNase I clearance forms a convergent mechanism of placental injury. Circulating biomarkers – cell-free DNA, myeloperoxidase‑DNA complexes, citrullinated histone H3, calprotectin, high mobility group box 1 (HMGB1) and therapeutic strategies – peptidylarginine deiminase 4 (PAD4) inhibitors, recombinant DNase I, hydroxychloroquine are systematized. Conclusion . The imbalance between NETs formation and degradation constitutes a cross-nosological hub of placenta-associated complications. Prospective studies are required to standardize biomarker assays and evaluate safety of targeted NETosis modulators in pregnancy.
DOI: 10.17749/2313-7347/ob.gyn.rep.2026.822
Authors: E. V. Ushakova, N. A. Apkadirova, E. Antoshchuk, Ya. A. Borovskaya, A. A. Gabitova, D. A. Zaytseva, V. V. Iatsuk, D. S. Kolomiets, A. G. Dolgopolov, M. A. Demidenko, A. A. Akhmadeeva, A. E. Mishchenko, D. N. Gadzhieva, A. S. Poletaeva
Institutions: Ministry of Health of the Russian Federation, Bashkir State Medical University, North-Western State Medical University named after I.I. Mechnikov, First Pavlov State Medical University of St. Petersburg, Saint Petersburg State Pediatric Medical University, Rostov State Medical University, Krasnoyarsk State Medical University, Ural State Medical University, Tver State Medical University, Yaroslavl State Medical Academy
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $142
OpenAlex ID: W7224948067
FWCI:
Cites: 79
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Related to: 10