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This study explores the effects of nicotinamide mononucleotide (NMN) in a letrozole-induced PCOS mouse model, focusing on metabolic regulation. Letrozole-induced aromatase inhibition elevated androgen and reduced bile acid levels, linking liver dysfunction and gut imbalance to PCOS. Letrozole-treated mice exhibited disrupted estrous cycles, ovarian congestion, and elevated testosterone. NMN intervention alleviated hyperandrogenism, ovarian abnormalities, and bile acid decline but did not fully restore the estrous cycle or improve lipid profiles. Metabolomic analysis showed that NMN partially reversed bile acid and lipid metabolism disturbances. These findings highlight NMN\u2019s protective role in reducing hyperandrogenism and ovarian cyst formation. However, effective PCOS treatment should target liver and gut metabolism, not just ovarian symptoms, to mitigate systemic effects. Bile acid dysregulation may play a key role in PCOS progression and warrants further investigation.<\/jats:p>","DOI":"10.3390\/biology13121028","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:01:37Z","timestamp":1733716897000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nicotinamide Mononucleotide Alleviates Bile Acid Metabolism and Hormonal Dysregulation in Letrozole-Induced PCOS Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6837-8874","authenticated-orcid":false,"given":"Caifang","family":"Ren","sequence":"first","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"},{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3038-3535","authenticated-orcid":false,"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9887-7845","authenticated-orcid":false,"given":"Junjie","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzi","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengrong","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang 212013, China"},{"name":"Hematological Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum. 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