{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:14:09Z","timestamp":1792588449459,"version":"4.5.0"},"reference-count":180,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preeclampsia is a pregnancy-specific multisystem disorder and a major cause of maternal and perinatal morbidity and mortality worldwide. This narrative review summarizes current evidence on the principal risk factors and pathophysiological mechanisms involved in its development. The disease is best explained by the two-stage model: in stage 1, inadequate trophoblast invasion and incomplete spiral artery remodeling lead to placental hypoperfusion, hypoxia, and oxidative stress; in stage 2, the hypoxic placenta releases anti-angiogenic and pro-inflammatory factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), which trigger systemic endothelial dysfunction and the maternal clinical syndrome. The review highlights the central role of angiogenic imbalance, immune dysregulation, and chronic inflammation in disease progression. Particular emphasis is placed on maternal risk factors such as primiparity, advanced maternal age, obesity, diabetes mellitus, chronic hypertension, multiple pregnancy, prior preeclampsia, genetic susceptibility, and epigenetic regulation. We also emphasize the contribution of microRNAs in relation to placental hypoxia, trophoblast invasion, angiogenesis, endothelial injury and microchimerism to the development of preeclampsia. The review also examines the role of T helper 1 (Th1)\/Th2\/Th17\/regulatory T cells (Treg) imbalance and uterine natural killer cell dysfunction at the maternal\u2013fetal interface. Improved understanding of these interconnected mechanisms may support earlier diagnosis, better risk stratification, and the development of targeted preventive and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27104281","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Understanding Preeclampsia: Integrating Placental Dysfunction, Immune Dysregulation and microRNA-Mediated Epigenetic Regulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-5775","authenticated-orcid":false,"given":"Lucia Maria","family":"Procopciuc","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Valentina","family":"Caracostea","sequence":"additional","affiliation":[{"name":"Medicover Hospital, Suceagu, 407062 Cluj, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0944-3161","authenticated-orcid":false,"given":"Adriana Corina","family":"Hangan","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Pharmacy, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4920-4760","authenticated-orcid":false,"given":"Roxana Liana","family":"Lucaciu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0140-6736(00)03577-7","article-title":"Pathogenesis and genetics of pre-eclampsia","volume":"357","author":"Roberts","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0140-6736(10)60279-6","article-title":"Pre-eclampsia","volume":"376","author":"Steegers","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dickerson, A.G., Joseph, C.A., and Kashfi, K. 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