Oocyte‐specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early‐growing follicles by mitochondrial fission defect‐reactive oxygen species‐DNA damage

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

Abstract Background Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. Methods and results We generated eukaryotic factor 5 ( Eif5 ) conditional knockout mice aiming to investigate function of eIF5 during oocyte growth follicle development. Here, we demonstrated that deletion mouse primordial growing oocytes both resulted apoptosis within early‐growing follicles. Further studies revealed downregulated levels mitochondrial fission‐related proteins (p‐DRP1, FIS1, MFF MTFR) upregulated integrated stress response‐related (AARS1, SHMT2 SLC7A1) genes Atf4 , Ddit3 Fgf21 ). Consistent this, dysfunction characterized by elongated form, aggregated distribution beneath membrane, decreased adenosine triphosphate content mtDNA copy numbers, excessive accumulation reactive oxygen species (ROS) superoxide. Meanwhile, led a significant increase DNA damage response (γH2AX, p‐CHK2 p‐p53) proapoptotic (PUMA BAX), as well decrease anti‐apoptotic protein BCL‐xL. Conclusion These findings indicate follicles via fission defects, ROS damage. This study provides new insights into pathogenesis, genetic diagnosis potential therapeutic targets for POI. Key points leads arrest impairs proteins, followed dysfunction. Depletion causes pathway.

Language: Английский

ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Language: Английский