{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:22:35Z","timestamp":1790997755026,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/NHLBI","award":["R01HL163234"],"award-info":[{"award-number":["R01HL163234"]}]},{"name":"National Institutes of Health\/NHLBI","award":["R03HL162756"],"award-info":[{"award-number":["R03HL162756"]}]},{"name":"Preeclampsia Foundation","award":["R01HL163234"],"award-info":[{"award-number":["R01HL163234"]}]},{"name":"Preeclampsia Foundation","award":["R03HL162756"],"award-info":[{"award-number":["R03HL162756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality worldwide, with the placenta playing a central role in disease pathophysiology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying PE, focusing on placental genes, proteins, and genetic variants identified through multi-omic approaches. Transcriptomic studies in bulk placental tissue have identified many dysregulated genes in the PE placenta, including the PE signature gene, Fms-like tyrosine kinase 1 (FLT1). Emerging single-cell level transcriptomic data have revealed key cell types and molecular signatures implicated in placental dysfunction and PE. However, the considerable variability among studies underscores the need for standardized methodologies and larger sample sizes to enhance the reproducibility of results. Proteomic profiling of PE placentas has identified numerous PE-associated proteins, offering insights into potential biomarkers and pathways implicated in PE pathogenesis. Despite significant progress, challenges such as inconsistencies in study findings and lack of validation persist. Recent fetal genome-wide association studies have identified multiple genetic loci associated with PE, with ongoing efforts to elucidate their impact on placental gene expression and function. Future directions include the integration of multi-omic data, validation of findings in diverse PE populations and clinical subtypes, and the development of analytical approaches and experimental models to study the complex interplay of placental and maternal factors in PE etiology. These insights hold promise for improving risk prediction, diagnosis, and management of PE, ultimately reducing its burden on maternal and neonatal health.<\/jats:p>","DOI":"10.3390\/ijms25179343","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:54:10Z","timestamp":1724846050000},"page":"9343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Placental Origins of Preeclampsia: Insights from Multi-Omic Studies"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-8807","authenticated-orcid":false,"given":"Chang","family":"Cao","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Saxena","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-3724","authenticated-orcid":false,"given":"Kathryn J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1001\/jama.2021.14781","article-title":"Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: US Preventive Services Task Force Recommendation Statement","volume":"326","author":"Davidson","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat. 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