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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\u2010specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2\u2010 to 4\u2010cell 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\u2010cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS\u2010related GTP\u2010binding 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.<\/jats:p>","DOI":"10.1002\/advs.202308823","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T15:34:08Z","timestamp":1726587248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["VPS34 Governs Oocyte Developmental Competence by Regulating Mito\/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-6601","authenticated-orcid":false,"given":"Wenwen","family":"Liu","sequence":"first","affiliation":[{"name":"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 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