An Exploratory Proteomics Study of Autoimmune Premature Ovarian Insufficiency in a Mouse Model

ABSTRACT: Premature ovarian insufficiency (POI) impairs fertility and health in reproductive-age women, with autoimmune factors contributing to 4-30% of cases[1]. To investigate immune dysregulation in POI, we developed two mouse models using pZP3 induction: regular immune (RE-POI) and enhanced immune (EN-POI) cycles. The EN-POI model exhibited stable, irreversible ovarian dysfunction, including disrupted estrous cycles, hormonal changes (elevated FSH, decreased AMH and estradiol), follicular depletion, and infertility. Immune profiling revealed increased CD4+ T cells and decreased regulatory T cells in the spleen, elevated inflammatory cytokines (e.g., interferon-γ, CCL4, CCL5) in serum, and ovarian fibrosis. Proteomics identified 198 differentially expressed proteins enriched in immune and inflammatory pathways. Network analysis highlighted six hub proteins, such as MMP9, ISG15, and IKBKE, with expressions negatively correlating with ovarian reserve markers in human POI. This study establishes a stable autoimmune POI model, elucidates T-cell imbalance with cytokine storm and fibrosis, and identifies key molecules linking immune abnormalities to ovarian failure, offering new insights for POI research.

ORGANISM(S): Mus Musculus

SUBMITTER: Feiyang Diao  

PROVIDER: PXD077415 | iProX | Mon Apr 20 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX