Sirtuin 5-driven meiotic spindle assembly and actin-based migration in mouse oocyte meiosis
Cong Ma,
Xueke Zhang,
Yingying Zhang,
Hongzhen Ruan,
Xiaofeng Xu,
Caiyun Wu,
Zhiming Ding,
Yunxia Cao
Affiliations
Cong Ma
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No.81 Meishan Road, Hefei, 230032, China
Xueke Zhang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No.81 Meishan Road, Hefei, 230032, China
Yingying Zhang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China
Hongzhen Ruan
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China
Xiaofeng Xu
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China
Caiyun Wu
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China
Zhiming Ding
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No.81 Meishan Road, Hefei, 230032, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China.
Yunxia Cao
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No.81 Meishan Road, Hefei, 230032, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No.81 Meishan Road, Hefei, 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Anhui Provincial Institute of Translational Medicine, No.81 Meishan Road, Hefei, 230032, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China.
Sirtuin 5 (Sirt5), a member of the Sirtuin family, is involved in various intracellular biological processes. However, the function of Sirt5 in oocyte maturation has not been clearly elucidated. In this study, we observed that Sirt5 was persistently expressed during the meiotic division of mouse oocytes, with a notable decline in expression in aging oocytes. Sirt5 inhibition led to the failure of the first polar body extrusion and induced cell cycle arrest, indicative of unsuccessful oocyte maturation. Furthermore, Sirt5 inhibition was associated with the extrusion of abnormally large polar bodies, suggesting disrupted asymmetric oocyte division. Mechanistically, the inhibition of Sirt5 resulted in aberrant spindle assembly and disordered chromosome alignment in oocytes. Moreover, Sirt5 inhibition caused the spindle to be centrally located in the oocyte without migrating to the cortical region, consequently preventing the formation of the actin cap. Further investigation revealed that Sirt5 inhibition notably diminished the expression of phosphorylated cofilin and profilin1, while increasing cytoplasmic F-actin levels. These findings suggest that Sirt5 inhibition during oocyte maturation adversely affects spindle assembly and chromosome alignment and disrupts actin dynamics impairing spindle migration and contributing to the failure of symmetric oocyte division and maturation.