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Updated: Apr 16, 2026
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes
Liang Zhang1,2, Longsen Han1, Rujun Ma1,3
1a College of Animal Science & Technology; Nanjing Agricultural University ; Nanjing , China.
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.
Insights
Maternal obesity increases oxidative stress in oocytes. Sirtuin 3 (Sirt3) protects against this by deacetylating superoxide dismutase 2 (SOD2), preventing meiotic defects.
Area of Science:
- Reproductive Biology
- Cellular Metabolism
- Maternal Health
Background:
- Maternal obesity is linked to oocyte oxidative stress and meiotic errors.
- The molecular mechanisms underlying these defects remain largely unknown.
Purpose of the Study:
- To investigate the role of Sirtuin 3 (Sirt3) in regulating oxidative stress and meiotic integrity in oocytes from a mouse model of maternal obesity.
- To elucidate the specific molecular targets and pathways involved in Sirt3-mediated protection.
Main Methods:
- Utilized a high-fat diet (HFD) mouse model to induce obesity.
- Assessed reactive oxygen species (ROS) levels, Sirt3 expression, and oocyte meiotic status (spindle organization, chromosome alignment).
- Employed genetic manipulation (Sirt3 depletion/overexpression) and site-directed mutagenesis (SOD2 acetylation mimic/non-mimic) to study protein function.
Main Results:
- HFD-induced oocytes exhibited elevated ROS and reduced Sirt3 expression.
- Sirt3 depletion increased ROS, while Sirt3 overexpression reduced ROS and rescued meiotic defects in HFD oocytes.
- Sirt3 deacetylated superoxide dismutase 2 (SOD2) at lysine 68 (SOD2K68).
- Acetylation-mimetic SOD2K68Q mutant significantly increased ROS, while the non-acetylatable SOD2K68R mutant partially rescued HFD-induced oocyte defects.
Conclusions:
- Sirt3 plays a critical role in maintaining ROS homeostasis in oocytes.
- Sirt3-dependent deacetylation of SOD2 protects oocytes from oxidative stress and meiotic abnormalities associated with maternal obesity.
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