Adoptive transfers of CD4⁺ CD25⁺ Tregs partially alleviate mouse premature ovarian insufficiency

This study was designed to investigate the protective effect of CD4⁺ CD25⁺ regulatory T cells (Tregs) against zona pellucida glycoprotein 3 peptide (pZP3) immunization-induced premature ovarian insufficiency (POI) in mice. A mouse POI model was induced by two subcutaneous injections of pZP3 (50 nmol/L). Mice in the pZP3-Treg group were intraperitoneally injected with 5 × 10⁵ CD4⁺ CD25⁺ Tregs after the POI model was established. Sex hormone levels, follicle numbers, apoptotic events, and the Akt/FOXO3a signaling pathway molecules in the ovaries were assessed. Compared with control group, the weight of ovaries in both pZP3 group and pZP3-Treg group was decreased and no difference was found between them. The number of follicles in the Treg transferred mice, like in pZP3 group, was significantly reduced compared to the control group, but showed a modest improvement when compared the pZP3 group alone. Significantly lower serum concentrations of follicle-stimulating hormone, luteinizing hormone, and anti-zona pellucida antibodies (AZPAbs) were found, while the concentrations of estradiol and anti-Mullerian hormone increased. In mechanism, Treg cell transfer to ZP3 treated mice restored the levels of Caspase3 to control levels, and partially restored Bax, however, had no effect on Bcl-2. Moreover, Treg cell transfer to ZP3 treated mice partially restored the levels of Akt and FOXO3a, and partially restored the ratios of p-Akt/Akt and p-FOXO3a/FOXO3a. In conclusion, Treg cells improved some aspects of ZP3-induced POI which may be mediate by suppressing ovarian cells apoptosis and involving the Akt/FOXO3a signaling pathway. Therefore, Treg cells may be protective against autoimmune POI.