{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T06:25:26Z","timestamp":1790576726795,"version":"4.1.0"},"reference-count":135,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age characterized by a spectrum of clinical, metabolic, reproductive, and psychological abnormalities. This syndrome is associated with significant long-term health risks, necessitating elucidation of its pathophysiology, early diagnosis, and comprehensive management strategies. Several contributory factors in PCOS, including androgen excess and insulin resistance, collectively enhance oxidative stress, which subsequently leads to mitochondrial dysfunction. However, the precise mechanisms through which oxidative stress induces mitochondrial dysfunction remain incompletely understood. Comprehensive searches of electronic databases were conducted to identify relevant studies published up to 30 September 2024. Mitochondria, the primary sites of reactive oxygen species (ROS) generation, play critical roles in energy metabolism and cellular homeostasis. Oxidative stress can inflict damage on components, including lipids, proteins, and DNA. Damage to mitochondrial DNA (mtDNA), which lacks efficient repair mechanisms, may result in mutations that impair mitochondrial function. Dysfunctional mitochondrial activity further amplifies ROS production, thereby perpetuating oxidative stress. These disruptions are implicated in the complications associated with the syndrome. Advances in genetic analysis technologies, including next-generation sequencing, have identified point mutations and deletions in mtDNA, drawing significant attention to their association with oxidative stress. Emerging data from mtDNA mutation analyses challenge conventional paradigms and provide new insights into the role of oxidative stress in mitochondrial dysfunction. We are rethinking the pathogenesis of PCOS based on these database analyses. In conclusion, this review explores the intricate relationship between oxidative stress, mtDNA mutations, and mitochondrial dysfunction, offers an updated perspective on the pathophysiology of PCOS, and outlines directions for future research.<\/jats:p>","DOI":"10.3390\/ijms26031172","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T10:36:28Z","timestamp":1738146988000},"page":"1172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-6269","authenticated-orcid":false,"given":"Hiroshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Medicine, Kei Oushin Clinic, 5-2-6 Naruo-cho, Nishinomiya 663-8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Prefecture General Medical Center, 2-897-5 Shichijyonishi-machi, Nara 630-8581, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shigetomi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Gynecology and Reproductive Medicine, Aska Ladies Clinic, 3-3-17 Kitatomigaoka-cho, Nara 634-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Teede, H., Deeks, A., and Moran, L. 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