{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:55:31Z","timestamp":1789156531416,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"The Research Council of Norway","doi-asserted-by":"publisher","award":["223255"],"award-info":[{"award-number":["223255"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"The Research Council of Norway","doi-asserted-by":"publisher","award":["223250"],"award-info":[{"award-number":["223250"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004590","name":"Central Norway Regional Health Authority","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100004590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Utero-placental development in pregnancy depends on direct maternal\u2013fetal interaction in the uterine wall decidua. Abnormal uterine vascular remodeling preceding placental oxidative stress and placental dysfunction are associated with preeclampsia and fetal growth restriction (FGR). Oxidative stress is counteracted by antioxidants and oxidative repair mechanisms regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). We aimed to determine the decidual regulation of the oxidative-stress response by NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) in normal pregnancies and preeclamptic pregnancies with and without FGR. Decidual tissue from 145 pregnancies at delivery was assessed for oxidative stress, non-enzymatic antioxidant capacity, cellular NRF2- and KEAP1-protein expression, and NRF2-regulated transcriptional activation. Preeclampsia combined with FGR was associated with an increased oxidative-stress level and NRF2-regulated gene expression in the decidua, while decidual NRF2- and KEAP1-protein expression was unaffected. Although preeclampsia with normal fetal growth also showed increased decidual oxidative stress, NRF2-regulated gene expression was reduced, and KEAP1-protein expression was increased in areas of high trophoblast density. The trophoblast-dependent KEAP1-protein expression in preeclampsia with normal fetal growth indicates control of decidual oxidative stress by maternal\u2013fetal interaction and underscores the importance of discriminating between preeclampsia with and without FGR.<\/jats:p>","DOI":"10.3390\/ijms23041966","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:40:17Z","timestamp":1644547217000},"page":"1966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Divergent Regulation of Decidual Oxidative-Stress Response by NRF2 and KEAP1 in Preeclampsia with and without Fetal Growth Restriction"],"prefix":"10.3390","volume":"23","author":[{"given":"Siv Boon","family":"Mundal","sequence":"first","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Women\u2019s Health and Perinatology Research Group, Department of Clinical Medicine, UiT\u2014The Arctic University of Norway, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-8211","authenticated-orcid":false,"given":"Johanne Johnsen","family":"Rakner","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Brettas","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lobke Marijn","family":"Gierman","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Austdal","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway"},{"name":"Department of Research, Stavanger University Hospital, 4068 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-9558","authenticated-orcid":false,"given":"Purusotam","family":"Basnet","sequence":"additional","affiliation":[{"name":"Women\u2019s Health and Perinatology Research Group, Department of Clinical Medicine, UiT\u2014The Arctic University of Norway, 9037 Troms\u00f8, Norway"},{"name":"Department of Obstetrics and Gynecology, University Hospital of Northern Norway, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattijs","family":"Elschot","sequence":"additional","affiliation":[{"name":"Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siril Skaret","family":"Bakke","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Ostrop","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-8518","authenticated-orcid":false,"given":"Liv Cecilie Vestrheim","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Haukeland University Hospital, 5058 Bergen, Norway"},{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Keith","family":"Moses","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-3107","authenticated-orcid":false,"given":"Ganesh","family":"Acharya","sequence":"additional","affiliation":[{"name":"Women\u2019s Health and Perinatology Research Group, Department of Clinical Medicine, UiT\u2014The Arctic University of Norway, 9037 Troms\u00f8, Norway"},{"name":"Department of Clinical Science, Division of Obstetrics and Gynecology, Intervention and Technology, Karolinska Institutet, 141 86 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-2770","authenticated-orcid":false,"given":"Line","family":"Bj\u00f8rge","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Haukeland University Hospital, 5058 Bergen, Norway"},{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-7684","authenticated-orcid":false,"given":"Ann-Charlotte","family":"Iversen","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S745","DOI":"10.1016\/j.ajog.2017.11.577","article-title":"Pathophysiology of placental-derived fetal growth restriction","volume":"218","author":"Burton","year":"2018","journal-title":"Am. 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