Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes

Liang Zhang, Longsen Han, Rujun Ma, Xiaojing Hou, Yang Yu, Shaochen Sun, Yinxue Xu, Tim Schedl, Kelle H. Moley, Qiang Wang

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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.

Original languageEnglish
Pages (from-to)2959-2968
Number of pages10
JournalCell Cycle
Issue number18
StatePublished - 2015


  • Obese
  • Oocyte
  • Oxidative stress
  • SOD
  • Sirtuin


Dive into the research topics of 'Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes'. Together they form a unique fingerprint.

Cite this