Language

English

Publication Date

5-13-2025

Journal

Biology of Reproduction

DOI

10.1093/biolre/ioaf035

PMID

39982420

PMCID

PMC13017552

PubMedCentral® Posted Date

2-21-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may drive the premature follicle loss phenotype. Label-free mass spectrometry results showed that 238 proteins were significantly altered more than 2-fold (p <  0.05). Proteins upregulated in the Ube2i conditional knockout ovaries included those involved in mRNA splicing and WNT signaling, while those downregulated were related to metabolism, mitochondria, and the maternal effect proteins NLRP2 and NLRP9B. The majority of differentially expressed proteins showed no change by transcriptome analysis, indicating protein level regulation and revealing potential SUMOylation targets with necessary roles in oocyte and follicle development.

Keywords

Animals, Female, Oocytes, Sumoylation, Mice, Ovarian Follicle, Mice, Knockout, Ubiquitin-Conjugating Enzymes, Oogenesis, folliculogenesis, infertility, posttranslational protein modification, proteomics, ovary, SUMOylation

Published Open-Access

yes

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