Human Umbilical Cord Mesenchymal Stem Cells Alleviate Autoimmune POI Associated With Downregulated UBE2N-Mediated Ovarian Inflammation.

OBJECTIVE: To evaluate the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a murine model of autoimmune premature ovarian insufficiency (POI), and to investigate the association between ubiquitin-conjugating enzyme E2N (UBE2N) expression and disease progression as well as treatment response. METHODS: Autoimmune POI was induced in female BALB/c mice by zona pellucida glycoprotein 3 peptide (pZP3) immunization. Thirty mice were randomly assigned to Control, POI Model, and hUC-MSC Treatment groups. Treated mice received weekly tail vein injections of hUC-MSCs (1 × 106 cells/mouse) for 4 weeks. Estrous cyclicity, fertility, ovarian histopathology, peripheral Th17/Treg balance, and the expression of IL-17, IFN-γ, and UBE2N were evaluated by immunohistochemistry. RESULTS: Compared with the POI Model group, hUC-MSC treatment restored regular estrous cyclicity, improved ovarian morphology, and increased litter size. Flow cytometry showed correction of the abnormal Th17/Treg imbalance in treated mice. Immunohistochemistry revealed marked upregulation of UBE2N, IL-17, and IFN-γ in ovarian tissue from POI mice, whereas hUC-MSC administration significantly reduced their expression. No treatment-related adverse effects were observed. CONCLUSION: hUC-MSCs effectively alleviated ovarian dysfunction in autoimmune POI mice. The therapeutic improvement was accompanied by systemic immune rebalancing and decreased aberrant ovarian UBE2N expression, indicating UBE2N as a candidate inflammatory biomarker associated with autoimmune ovarian injury and immune dysregulation.