{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:18:11Z","timestamp":1788801491534,"version":"build-2803163510"},"reference-count":348,"publisher":"Portland Press Ltd.","issue":"24","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:p>Preeclampsia, defined by hypertension and end organ damage after 20 weeks of gestation, remains a significant cause of maternal and fetal morbidity and mortality. This disorder has a diverse clinical presentation and is likely driven by several underlying mechanisms, many remaining poorly understood. However, there is emerging evidence that epigenetic regulators, including histone deacetylases (HDACs), may contribute to the pathophysiology of preeclampsia. Of the many HDACs, HDAC9 is particularly intriguing in the context of preeclampsia due to its decreased presence in preeclamptic placenta and prominent role in controlling trophoblast, vascular, and immune behavior, which are often dysregulated in this condition. This review focuses specifically on HDAC9, detailing its expression patterns, molecular properties, known and hypothesized targets at the maternal\u2013fetal interface, and potential causes of dysregulation. Special emphasis is placed on its impact on trophoblast function, immune signaling, angiogenesis, and G-protein\u2013coupled receptor pathways, which are frequently disrupted in preeclampsia. Although current evidence for altered HDAC9 expression in this disorder is confined to the placenta, its potential role in maternal physiology remains an open and important question. By integrating findings from placental biology and disorders with overlapping pathways such as cardiovascular disease and cancer research, this review aims to establish a framework for understanding how HDAC9 contributes to preeclampsia pathogenesis and to identify promising directions for future investigation and therapeutic development.<\/jats:p>","DOI":"10.1042\/cs20242385","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:42:47Z","timestamp":1766155367000},"page":"1769-1798","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The multifactorial role of HDAC9 at the maternal\u2013fetal interface in the pathogenesis of preeclampsia"],"prefix":"10.1042","volume":"139","author":[{"given":"Megan A.","family":"Opichka","sequence":"first","affiliation":[{"name":"1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"McIntosh","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"2Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"3Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-0873","authenticated-orcid":false,"given":"Justin L.","family":"Grobe","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"3Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"4Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"5Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226"},{"name":"6Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"2025122309063325600_CS-2024-2385C1","doi-asserted-by":"crossref","first-page":"f6564","DOI":"10.1136\/bmj.f6564","article-title":"Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis","volume":"347","author":"Ananth","year":"2013","journal-title":"BMJ"},{"key":"2025122309063325600_CS-2024-2385C2","doi-asserted-by":"crossref","first-page":"F1315","DOI":"10.1152\/ajprenal.00071.2020","article-title":"Preeclampsia beyond pregnancy: long-term consequences for mother and child","volume":"318","author":"Turbeville","year":"2020","journal-title":"Am. 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