{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T13:55:50Z","timestamp":1792936550857,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of China","award":["8162010801"],"award-info":[{"award-number":["8162010801"]}]},{"name":"Natural Science Foundation of China","award":["31971892"],"award-info":[{"award-number":["31971892"]}]},{"name":"Natural Science Foundation of China","award":["32170864"],"award-info":[{"award-number":["32170864"]}]},{"name":"Natural Science Foundation of China","award":["2017YFC1001404"],"award-info":[{"award-number":["2017YFC1001404"]}]},{"name":"Natural Science Foundation of China","award":["2018YFC1002802"],"award-info":[{"award-number":["2018YFC1002802"]}]},{"name":"Natural Science Foundation of China","award":["82001574"],"award-info":[{"award-number":["82001574"]}]},{"name":"State Key Research and Development Program of China","award":["8162010801"],"award-info":[{"award-number":["8162010801"]}]},{"name":"State Key Research and Development Program of China","award":["31971892"],"award-info":[{"award-number":["31971892"]}]},{"name":"State Key Research and Development Program of China","award":["32170864"],"award-info":[{"award-number":["32170864"]}]},{"name":"State Key Research and Development Program of China","award":["2017YFC1001404"],"award-info":[{"award-number":["2017YFC1001404"]}]},{"name":"State Key Research and Development Program of China","award":["2018YFC1002802"],"award-info":[{"award-number":["2018YFC1002802"]}]},{"name":"State Key Research and Development Program of China","award":["82001574"],"award-info":[{"award-number":["82001574"]}]},{"name":"Natural Science Foundation of China","award":["8162010801"],"award-info":[{"award-number":["8162010801"]}]},{"name":"Natural Science Foundation of China","award":["31971892"],"award-info":[{"award-number":["31971892"]}]},{"name":"Natural Science Foundation of China","award":["32170864"],"award-info":[{"award-number":["32170864"]}]},{"name":"Natural Science Foundation of China","award":["2017YFC1001404"],"award-info":[{"award-number":["2017YFC1001404"]}]},{"name":"Natural Science Foundation of China","award":["2018YFC1002802"],"award-info":[{"award-number":["2018YFC1002802"]}]},{"name":"Natural Science Foundation of China","award":["82001574"],"award-info":[{"award-number":["82001574"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>We have previously demonstrated that placental 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2-HSD2) dysfunction contributes to PE pathogenesis. We sought to elucidate molecular mechanisms underlying 11\u03b2-HSD2 dysfunction-induced PE and to seek potential therapeutic targets using a 11\u03b2-HSD2 dysfunction-induced PE-like rat model as well as cultured extravillous trophoblasts (EVTs) since PE begins with impaired function of EVTs. In 11\u03b2-HSD2 dysfunction-induced PE-like rat model, we revealed that placental mitochondrial dysfunction occurred, which was associated with mitDNA instability and impaired mitochondrial dynamics, such as decreased optic atrophy 1 (OPA1) expression. MitoTEMPO treatment significantly alleviated the hallmark of PE-like features and improved mitDNA stability and mitochondrial dynamics in the placentas of rat PE-like model. In cultured human EVTs, we found that 11\u03b2-HSD2 dysfunction led to mitochondrial dysfunction and disrupted mtDNA stability. MitoTEMPO treatment improved impaired invasion and migration induced by 11\u03b2-HSD2 dysfunction in cultured EVTs. Further, we revealed that OPA1 was one of the key factors that mediated 11\u03b2-HSD2 dysfunction-induced excess ROS production, mitochondrial dysfunction and mtDNA reduction. Our data indicates that 11\u03b2-HSD2 dysfunction causes mitochondrial dysfunctions, which impairs trophoblast function and subsequently results in PE development. Our study immediately highlights that excess ROS is a potential therapeutic target for PE.<\/jats:p>","DOI":"10.3390\/antiox11081505","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"1505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11\u03b2-HSD2 Dysfunction via OPA1 and MtDNA Maintenance"],"prefix":"10.3390","volume":"11","author":[{"given":"Jing","family":"Long","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"},{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Navy Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshan","family":"Tang","sequence":"additional","affiliation":[{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"},{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dou","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"},{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqin","family":"Wang","sequence":"additional","affiliation":[{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Maternity and Child Health Hospital of Pudong New District, Shanghai 201206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Changhai Hospital, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruojin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-327X","authenticated-orcid":false,"given":"Xin","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha 410008, China"},{"name":"National International Joint Research Center for Medical Metabolomics, Xiangya Hospital Central South University, Changsha 410008, China"},{"name":"Department of Physiology, Navy Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","article-title":"Preeclampsia: Pathophysiology, Challenges, and Perspectives","volume":"124","author":"Rana","year":"2019","journal-title":"Circ. 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