Human Umbilical Cord Mesenchymal Stem Cells Alleviate Autoimmune
POI
Associated With Downregulated
UBE2N
‐Mediated Ovarian Inflammation
Jinwei Li, Xianghui Wen, Jiaoshi Zhao, Min Gao, Xubin Hao, Shenghui Wen, Liuzhong Zhou, Xinyu Wu, Xiqing Luo, Shuangyan Cao, Qiujing Wei, Budian Liu, Yiman Fu, Qing Lv, Jieruo Gu ABSTRACT
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 × 10 6 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.