UBE2V1 governs aging induced protein aggregation and developmental defects in oocytes and embryos

Abstract While protein aggregation is a well-documented factor in various age-related diseases, its specific impact on oocyte aging and the molecular mechanisms responsible remain poorly understood. In a mouse model of advanced maternal age, we observe that aging promotes ubiquitinated protein aggre...

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Bibliographic Details
Main Authors: Ling Li, Ying Liu, Xi He, Junqing Chen, Xiaowei Guan, Longsen Han
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08214-5
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Summary:Abstract While protein aggregation is a well-documented factor in various age-related diseases, its specific impact on oocyte aging and the molecular mechanisms responsible remain poorly understood. In a mouse model of advanced maternal age, we observe that aging promotes ubiquitinated protein aggregation in oocytes and embryos. Starting with this clue, we identify that the expression of ubiquitin-conjugating enzyme (E2) UBE2V1 in oocyte increases with age and correlates with aggresome formation. We further provide evidence that UBE2V1 positively regulates protein aggregates formation in oocyte under both physiological and stress conditions. Moreover, enhanced UBE2V1 expression mimics the phenotypes observed in aged oocytes. Notably, restoring UBE2V1 expression in aged oocytes and embryos not only alleviates aggresome formation but also partly ameliorates the age-related defects in oocyte maturation and embryo development. Thus, our findings provide a mechanistic link between UBE2V1 expression, protein aggregation and developmental defects in aged oocytes and embryos.
ISSN:2399-3642