{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:59:10Z","timestamp":1791644350248,"version":"4.3.4"},"reference-count":92,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VICTOR BABES UNIVERSITY OF MEDICINE AND PHARMACY TIMISOARA"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic pathways that converge across these disorders. Integrating morphological evidence with mechanistic data highlights how villous maldevelopment, shallow trophoblast invasion, and aberrant vascular remodeling translate into clinical disease. Advances in biomarker research have already transformed clinical care: the sFlt-1\/PlGF ratio is now established in the prediction and management of preeclampsia, while placental proteins such as PAPP-A and PP13, nucleic acid signatures including cfDNA, cfRNA and miRNAs, and extracellular vesicle cargo show promising potential for early, non-invasive detection of placental pathology. Multi-omics approaches, particularly single-cell and spatial transcriptomics combined with proteomic and metabolomic profiling, are paving the way for composite diagnostic panels that capture the polygenic and multicellular nature of placental disease. This review synthesizes current knowledge of molecular mechanisms, histological correlates, and translational biomarkers, and outlines how precision obstetrics may emerge from bridging mechanistic discoveries with clinical applications.<\/jats:p>","DOI":"10.3390\/ijms26199483","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Molecular Insights into Human Placentation: From Villous Morphogenesis to Pathological Pathways and Translational Biomarkers"],"prefix":"10.3390","volume":"26","author":[{"given":"Ioana","family":"Vornic","sequence":"first","affiliation":[{"name":"Discipline of Gynecology, Department Medicine, Vasile Goldis Western University, Liviu Rebreanu Boulevard, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Caprariu","sequence":"additional","affiliation":[{"name":"Discipline of Radiology and Medical Imaging, Department XV, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-7636","authenticated-orcid":false,"given":"Dorin","family":"Novacescu","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Cristina","family":"Barb","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Buciu","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"B\u0103loi","sequence":"additional","affiliation":[{"name":"Department X\u2013Surgery II, Disclipline Anaesthesia and Intensive Care, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Szekely","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Silviu","family":"Suciu","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Patrascu","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-179X","authenticated-orcid":false,"given":"Flavia","family":"Zara","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3060","authenticated-orcid":false,"given":"Cristina Stefania","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kn\u00f6fler, M., and Pollheimer, J. (2013). Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling. Front. 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