title: Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes.
abstract: Maternal obese environment has been reported to induce oxidative stress and meiotic defects in oocytes, however the underlying molecular mechanism remains unclear. Here, using mice fed a high fat diet (HFD) as an obesity model, we first detected enhanced reactive oxygen species (ROS) content and reduced Sirt3 expression in HFD oocytes. We further observed that specific depletion of Sirt3 in control oocytes elevates ROS levels while Sirt3 overexpression attenuates ROS production in HFD oocytes, with significant suppression of spindle disorganization and chromosome misalignment phenotypes that have been reported in the obesity model. Candidate screening revealed that the acetylation status of lysine 68 on superoxide dismutase (SOD2K68) is dependent on Sirt3 deacetylase activity in oocytes, and acetylation-mimetic mutant SOD2K68Q results in almost threefold increase in intracellular ROS. Moreover, we found that acetylation levels of SOD2K68 are increased by ~80% in HFD oocytes and importantly, that the non-acetylatable-mimetic mutant SOD2K68R is capable of partially rescuing their deficient phenotypes. Together, our data identify Sirt3 as an important player in modulating ROS homeostasis during oocyte development, and indicate that Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress and meiotic defects in oocytes under maternal obese conditions.
authors: a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.|b State Key Laboratory of Reproductive Medicine; Nanjing Medical University ; Nanjing , China.
authors: Liang
authors: L
authors: Zhang
authors: a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.
authors: Longsen
authors: L
authors: Han
authors: a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.|c College of Veterinary Medicine; Nanjing Agricultural University , Nanjing , China.
authors: Rujun
authors: R
authors: Ma
authors: b State Key Laboratory of Reproductive Medicine; Nanjing Medical University ; Nanjing , China.
authors: Xiaojing
authors: X
authors: Hou
authors: d Center of Reproductive Medicine; Department of Obstetrics and Gynecology; Peking University Third Hospital , Beijing , China.
authors: Yang
authors: Y
authors: Yu
authors: a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.
authors: Shaochen
authors: S
authors: Sun
authors: a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.
authors: Yinxue
authors: Y
authors: Xu
authors: e Washington University School of Medicine , St. Louis , MO USA.
authors: Tim
authors: T
authors: Schedl
authors: e Washington University School of Medicine , St. Louis , MO USA.
authors: Kelle H
authors: KH
authors: Moley
authors: b State Key Laboratory of Reproductive Medicine; Nanjing Medical University ; Nanjing , China.
authors: Qiang
authors: Q
authors: Wang
mesh_terms: D000107:Acetylation; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D006706:Homeostasis; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D009765:Obesity / Q000150:complications*; D009865:Oocytes / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C525046:Sirt3 protein, mouse; D013482:Superoxide Dismutase; D056566:Sirtuin 3
keywords: SOD; obese; oocyte; oxidative stress; sirtuin