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

Abstract

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.

Advances in the cellular immunological pathogenesis and related treatment of primary ovarian insufficiency

“…Anti-ovarian antibodies [26][27][28][29][30][31][32][33][34][35][36][37][38] zona pellucida antibodies zona pellucida AOA the ooplasm, the zona pellucida, the granulosa cells…”

“…The antibody against it has been suggested as a diagnostic marker of ovarian failure. 30 Immunizing C57BL/6 female mice to generate active HSP90 antibodies ultimately leads to ovarian failure. 38 These antibodies have been found for the early detection and adequately treatment of POI before irreversible ovarian dysfunction.…”

Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology

“…Similar to the protective function of Treg cells in other female reproductive organs, a role for tissue Treg cells for ovary gland homeostasis/physiology has been suggested (163). While their functional and transcriptional phenotype has not been addressed so far in greater detail, current data support a protective function as in a murine model for premature ovarian insufficiency adoptive transfer of Treg cells could alleviate ovarian cell apoptosis in a protein kinase B (Akt) signaling-dependent manner (164).…”

Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice

“…A total of 2 Â 10 5 CD4þCD25þ Treg cells in 200 mL of phosphate buffered saline (PBS) were transferred to a recipient mouse by intraperitoneal injection 1 day before MPTP treatment, in accordance with an optimized protocol from a previously published paper. 23…”