2. Academic Validation
  3. VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location

VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location

  • Adv Sci (Weinh). 2024 Sep 17:e2308823. doi: 10.1002/advs.202308823.
Wenwen Liu 1,  Kehan Wang 2,  Yuting Lin 3,  Lu Wang 4 5,  Xin Jin 4 6,  Yuexin Qiu 4,  Wenya Sun 4,  Ling Zhang 7,  Yan Sun 4,  Xiaowei Dou 4 8,  Shiming Luo 9,  Youqiang Su 10,  Qingyuan Sun 9,  Wenpei Xiang 7,  Feiyang Diao 3,  Jing Li 4 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
  • 2 State Key Laboratory of Reproductive Medicine and Offspring Health, Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, China.
  • 3 The Center for Clinical Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 212028, China.
  • 4 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
  • 5 Department of Reproductive Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, 061012, China.
  • 6 Department of Center of Reproductive Medicine, Wuxi Maternity and Child Health Care Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214200, China.
  • 7 Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
  • 8 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
  • 9 Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, 513023, China.
  • 10 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China.
  • 11 Innovation Center of Suzhou Nanjing Medical University, Suzhou, 430074, China.
PMID: 39287146 DOI: 10.1002/advs.202308823
Abstract

Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (Vps34) is renowned for its pivotal role in regulating Autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte-specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2- to 4-cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2-cell embryos. The findings further elucidated the regulation of Vps34 on the activity and subcellular translocation of RAS-related GTP-binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating Mitophagy via retrograde trafficking. Vps34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating Vps34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, Vps34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

Keywords

VPS34; autophagy; mitophagy; oocyte; retromer.

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