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20S proteasomes are required for ELVAs-mediated protein degradation during oocyte-to-embryo transition and aging

ABSTRACT: The degradation of maternal factors is essential for oocyte-to-embryo transition (OET). While extensive research has focused on maternal mRNA degradation, the mechanisms underlying maternal protein degradation remain poorly understood. ELVAs, the oocyte-specific membraneless structure which comprises proteasomes, endolysosomes and autophagosomes, are required for protein degradation in maturing oocytes and zygotes. In this study, we embloyed oocyte-specific Psma7 knockout, targeting the α4 subunit of 20S proteasome, to investigate the physiological function of proteasomes in ELVAs-mediated protein degradation. PSMA7-deficiency destabilizes 20S proteasome components and disrupts ELVAs assembly and spatial organization, resulting in the accumulation of ubiquitinated proteins in both oocytes and zygotes. Consequently, maternal PSMA7-deletion results in female infertility, manifested by impaired oocyte maturation and developmental arrest at the 1- to 2-cell stage. Furthermore, in oocytes from both aged mice and women, reduced proteasome abundance and aberrations in ELVAs distribution and activity were found, providing a mechanistic explanation for the diminished developmental competence aged oocytes. Taken together, our findings elucidate the critical function of proteasome-regulated proteostasis in oocyte quality control during OET and reproductive aging in females.

ORGANISM(S): Mus musculus

PROVIDER: GSE293047 | GEO | 2026/04/27

REPOSITORIES: GEO

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