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The aim of this study was to determine how obesity impairs sperm mitochondrial structural integrity and function, and reduces sperm quality in both overweight\/obese men and mice on a high\u2010fat diet (HFD). Mice fed the HFD demonstrated higher body weight and increased abdominal fat content than those fed the control diet. Such effects accompanied the decline in antioxidant enzymes, such as glutathione peroxidase (GPX) and catalase and superoxide dismutase (SOD) in testicular and epidydimal tissues. Moreover, malondialdehyde (MDA) content significantly increased in sera. Mature sperm in HFD mice demonstrated higher oxidative stress, including increased mitochondrial reactive oxygen species (ROS) levels and decreased protein expression of GPX1, which may impair mitochondrial structural integrity and reduce mitochondrial membrane potential (MMP) and ATP production. Moreover, cyclic AMPK phosphorylation status increased, whereas sperm motility declined in the HFD mice. Clinical studies demonstrated that being overweight\/obese reduced SOD enzyme activity in the seminal plasma and increased ROS in sperm, accompanied by lower MMP and low\u2010quality sperm. Furthermore, ATP content in the sperm was negatively correlated with increases in the BMI of all clinical subjects. In conclusion, our results suggest that excessive fat intake had similar disruptive effects on sperm mitochondrial structure and function, as well as oxidative stress levels in humans and mice, which in turn induced lower sperm motility. This agreement strengthens the notion that fat\u2010induced increases in ROS and impaired mitochondrial function contribute to male subfertility.<\/jats:p>","DOI":"10.1002\/2211-5463.13589","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T13:20:07Z","timestamp":1677849607000},"page":"763-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Obesity\u2010induced oxidative stress and mitochondrial dysfunction negatively affect sperm quality"],"prefix":"10.1002","volume":"13","author":[{"given":"Jia","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Fan","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center of Ruijin Hospital Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihua","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunran","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2700-922X","authenticated-orcid":false,"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3510-7313","authenticated-orcid":false,"given":"Zhide","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine Shanghai Jiao Tong University School of Medicine  China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO(2018)WHO fact sheet No 311. 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