journal article·2024-11Open access

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

Wenwen Liu, Kehan Wang, Yuting Lin, Lu Wang, Xin Jin, Yuexin Qiu, Wenya Sun, Ling Zhang, Yan Sun, Xiaowei Dou, Shiming Luo, Youqiang Su, Qingyuan Sun, Wenpei Xiang, Feiyang Diao, Jing Li

Advanced Science· Volume 11· Issue 41

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Autophagy in Disease and Therapy · Epigenetics and DNA Methylation · Genetic and Kidney Cyst Diseases

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

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

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

State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 China

Department of Reproductive Medicine Cangzhou Central Hospital Cangzhou Hebei 061012 China

Department of Center of Reproductive Medicine Wuxi Maternity and Child Health Care Hospital Nanjing Medical University Wuxi Jiangsu 214200 China

Institute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430074 China

Department of Obstetrics and Gynecology The Second Affiliated Hospital of Nanjing Medical University Nanjing Medical University Nanjing Jiangsu 210011 China

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

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology School of Life Sciences Shandong University Qingdao Shandong 266237 China

Innovation Center of Suzhou Nanjing Medical University Suzhou 430074 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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