{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:49:11Z","timestamp":1792014551417,"version":"4.4.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100006310","name":"Swedish Medical Research Council","doi-asserted-by":"publisher","award":["10380"],"award-info":[{"award-number":["10380"]}],"id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish government and the county councils","award":["ALFGBG-147791"],"award-info":[{"award-number":["ALFGBG-147791"]}]},{"name":"Jane and Dan Olsson\u2019s Foundation to H.B. and L.R.S"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004399"],"award-info":[{"award-number":["82004399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Medical University High-level University Construction Talents Fund","award":["B185006010046"],"award-info":[{"award-number":["B185006010046"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2019A1515110265"],"award-info":[{"award-number":["2019A1515110265"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014437","name":"Wenner-Gren Foundations","doi-asserted-by":"publisher","award":["RSh2019-0063"],"award-info":[{"award-number":["RSh2019-0063"]}],"id":[{"id":"10.13039\/100014437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81774136"],"award-info":[{"award-number":["81774136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Foundation for Postdoctoral Researchers of Heilongjiang Province"},{"name":"Project of Science Foundation of Heilongjiang University of Chinese Medicine and the Project of Excellent Innovation Talents of Heilongjiang University of Chinese Medicine"},{"name":"A Royal Society Dorothy Hodgkin Research Fellowship and Lister Institute Research Prize"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The mechanisms that link hyperandrogenism and insulin (INS) resistance (HAIR) to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investigated the efficacy and molecular mechanism of action of the antioxidant N-acetylcysteine (NAC) in reversing gravid uterine and placental ferroptosis in pregnant rats exposed to 5\u03b1-dihydrotestosterone (DHT) and INS. Molecular and histological analyses showed that NAC attenuated DHT and INS-induced uterine ferroptosis, including dose-dependent increases in anti-ferroptosis gene content. Changes in other molecular factors after NAC treatment were also observed in the placenta exposed to DHT and INS, such as increased glutathione peroxidase 4 protein level. Furthermore, increased apoptosis-inducing factor mitochondria-associated 2 mRNA expression was seen in the placenta but not in the uterus. Additionally, NAC was not sufficient to rescue DHT + INS-induced mitochondria-morphological abnormalities in the uterus, whereas the same treatment partially reversed such abnormalities in the placenta. Finally, we demonstrated that NAC selectively normalized uterine leukemia inhibitory factor, osteopontin\/secreted phosphoprotein 1, progesterone receptor, homeobox A11 mRNA expression and placental estrogen-related receptor beta and trophoblast-specific protein alpha mRNA expression. Collectively, our data provide insight into how NAC exerts beneficial effects on differentially attenuating gravid uterine and placental ferroptosis in a PCOS-like rat model with fetal loss. These results indicate that exogenous administration of NAC represents a potential therapeutic strategy in the treatment of HAIR-induced uterine and placental dysfunction.<\/jats:p>","DOI":"10.1093\/molehr\/gaab067","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T20:15:56Z","timestamp":1637180156000},"source":"Crossref","is-referenced-by-count":71,"title":["Suppression of uterine and placental ferroptosis by N-acetylcysteine in a rat model of polycystic ovary syndrome"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7731-5874","authenticated-orcid":false,"given":"Min","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"},{"name":"Institute of Integrated Traditional Chinese Medicine and Western Medicine, Guangzhou Medical University, Guangzhou, China"},{"name":"Department of Physiology and Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Nancy","family":"Sferruzzi-Perri","sequence":"additional","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1767-7344","authenticated-orcid":false,"given":"Xiaoke","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-613X","authenticated-orcid":false,"given":"Hongxia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"},{"name":"Institute of Integrated Traditional Chinese Medicine and Western Medicine, Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Br\u00e4nnstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-9570","authenticated-orcid":false,"given":"Linus R","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Physiology and Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Billig","sequence":"additional","affiliation":[{"name":"Department of Physiology and 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