{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:25:39Z","timestamp":1785363939016,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL049277"],"award-info":[{"award-number":["R01HL049277"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD101485"],"award-info":[{"award-number":["R01HD101485"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007890","name":"UNC-CH","doi-asserted-by":"crossref","award":["25VOUCH008"],"award-info":[{"award-number":["25VOUCH008"]}],"id":[{"id":"10.13039\/100007890","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Endothelin-1 (ET-1) is involved in the pathogenesis of preeclampsia. Mice (Edn1H\/+) having excess endothelin-1 developed preeclampsia-like phenotypes during pregnancy in a maternal genotype-dependent manner. Here, we investigated whether decidualization is impaired in Edn1H\/+ dams, and whether nicotinamide (a potent inhibitor of ET-1) exerts beneficial effect. We compared implantation sites between wild type (WT) and Edn1H\/+ dams with or without nicotinamide treatment. Implantation sites of Edn1H\/+ dams exhibited abnormal ectoplacental cones and sinusoids, along with reduced vascular density in the mesometrial regions of the decidua. VEGF levels were higher in the decidua of Edn1H\/+ dams compared with WT dams. Markers of decidualization were decreased in Edn1H\/+ dams. Nicotinamide supplementation corrected this abnormality. During differentiation (decidualization) of cultured human endometrial stomal cells, ET-1 impaired the upregulated expression of decidualization markers. The effect of ET-1 was reversed by nicotinamide. These results show nicotinamide counteracts the detrimental effects of ET-1 on endometrial decidualization and has potential to improve embryo implantation and subsequent pregnancy outcomes.<\/jats:p>","DOI":"10.3390\/cells14211645","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T08:41:08Z","timestamp":1761122468000},"page":"1645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nicotinamide Counteracts the Detrimental Effect of Endothelin-1 on Uterine Decidualization During Early Pregnancy by Influencing EDNRB"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuye","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meitong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Kayashima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7301-2698","authenticated-orcid":false,"given":"Jiayi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Golden LEAF Biomanufacturing Training and Education Center, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Bowser","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-2020","authenticated-orcid":false,"given":"Xianwen","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-3299","authenticated-orcid":false,"given":"Nobuyo","family":"Maeda-Smithies","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-5077","authenticated-orcid":false,"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0002-9378(97)80014-2","article-title":"Endothelin receptor A antagonism prevents hypoxia-induced intrauterine growth restriction in the rat","volume":"176","author":"Thaete","year":"1997","journal-title":"Am. 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