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We examined circulating and placental SEMA3A levels in women with healthy pregnancies, those with hypertensive disorders of pregnancy with appropriate-for-gestational-age fetuses, and hypertensive pregnancies complicated by fetal growth restriction, supplementing these analyses with in vitro endothelial assays. In maternal plasma and placental tissues, SEMA3A levels were elevated in hypertensive pregnancies, peaking in cases with fetal growth restriction. In cultured endothelial cells, SEMA3A disrupted cytoskeletal organization, compromised barrier stability, and altered cellular morphology. These changes were linked to lysosomal accumulation of its receptor neuropilin-1 and altered lysosomal function. Collectively, these findings identify SEMA3A as a regulator of endothelial cytoskeletal and lysosomal dynamics. By connecting in vitro mechanistic studies with in vivo pregnancy samples, this work underscores a novel role for SEMA3A that may be pertinent to hypertensive pregnancy and its complications.<\/jats:p>","DOI":"10.1042\/cs20258480","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:00:47Z","timestamp":1770904847000},"page":"409-425","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Semaphorin 3A disrupts endothelial structure and lysosomal function:\n                    <i>in vitro<\/i>\n                    mechanisms and\n                    <i>in vivo<\/i>\n                    evidence in hypertensive pregnancy"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1848-5950","authenticated-orcid":false,"given":"Gabriella","family":"Ferretti","sequence":"first","affiliation":[{"name":"1Unit of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-0367","authenticated-orcid":false,"given":"Sara","family":"Serafini","sequence":"additional","affiliation":[{"name":"1Unit of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"},{"name":"2Department of Medicine and Health Sciences, Centre for Research and Training in Medicine of Aging, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sarno","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Palese","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Abbruzzese","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca\u00a0R.","family":"Di Palo","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"De Simone","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Guida","sequence":"additional","affiliation":[{"name":"3Unit of Gynecology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-0107","authenticated-orcid":false,"given":"Carmela","family":"Matrone","sequence":"additional","affiliation":[{"name":"1Unit of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples, \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"2026030312264575600_B1","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1891\/NN-2024-0001","article-title":"Preeclampsia: short- and long-term effects","volume":"43","author":"Conley","year":"2024","journal-title":"Neonatal Netw."},{"key":"2026030312264575600_B2","doi-asserted-by":"publisher","first-page":"428","DOI":"10.5858\/arpa.2020-0027-OA","article-title":"Consensus definition of fetal growth restriction in intrauterine fetal death: a Delphi Procedure","volume":"145","author":"Beune","year":"2021","journal-title":"Arch. 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