{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:58:46Z","timestamp":1790585926339,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Preeclampsia (PE) affects 2%\u20138% of pregnancies globally and remains a leading cause of maternal and perinatal mortality. A central clinical gap is the absence of analytically and clinically validated non\u2010invasive biomarkers capable of predicting PE before symptom onset. Current clinical tools, including angiogenic markers (sFlt\u20101\/PlGF ratio) and first\u2010trimester risk algorithms, have limitations that underscore the need for complementary approaches. Placental extracellular vesicles (EVs)\u2014small particles released predominantly by syncytiotrophoblast cells\u2014are implicated across PE pathophysiology. Circulating total small EV (sEV) concentrations, typically 30\u2013150\u00a0nm and isolated by differential centrifugation or size\u2010exclusion chromatography, are measurably elevated in maternal circulation from the first trimester in women who develop PE; this operational, size\u2010 and isolation\u2010based definition does not by itself establish placental origin, which requires placental\u2010attribution markers (e.g., PLAP, syncytins) discussed in Section 2. Their molecular cargo, encompassing microRNAs (miR\u2010210, miR\u201015a\u20105p, miR\u2010520a\u20105p, miR\u2010146a\u20105p, miR\u201093\u20105p), anti\u2010angiogenic proteins (sFlt\u20101, sEng), and hypoxia markers (HIF\u20101\u03b1), reflects placental pathophysiology. Recent evidence has expanded the known pathophysiological reach of placental EVs: beyond endothelial dysfunction and angiogenic imbalance, they are now implicated in blood\u2010brain barrier disruption via claudin\u20105 (CLDN5) downregulation, supporting a plausible mechanistic link to neurological complications of PE. Proteomic profiling of EV fractions identifies molecularly distinct PE subtypes, enabling investigational subtype discrimination beyond current clinical criteria. Recent in vivo proof\u2010of\u2010concept evidence in a rat model demonstrates that amniotic fluid\u2010derived EV\u2010associated miR\u2010146a\u20105p ameliorates PE phenotypes, opening a preclinical therapeutic avenue. This narrative review synthesises evidence from a structured PubMed\/MEDLINE and Scopus search covering 2017\u2013March 2025 on placental EV biogenesis, cargo heterogeneity, immune modulation, organ\u2010specific pathological consequences, and translational potential as first\u2010trimester liquid biopsy candidates. Methodological standardization challenges and future research priorities are discussed.<\/jats:p>","DOI":"10.1111\/aji.70315","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:15:02Z","timestamp":1788023702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental Extracellular Vesicles in Preeclampsia: Molecular Cargo, Pathophysiological Roles, and Emerging Diagnostic and Therapeutic Frontiers"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4945-4542","authenticated-orcid":false,"given":"Marhaen","family":"Hardjo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine Hasanuddin University  Makassar, South Sulawesi Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-2110","authenticated-orcid":false,"given":"Alfi","family":"Sophian","sequence":"additional","affiliation":[{"name":"Food and Drug Investigation Laboratory The Indonesian Food and Drug Authority  Jakarta Pusat Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"StatPearls.Preeclampsia [Internet]. 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