The role of mTOR signaling pathway-mediated Treg/Th17 cell imbalance in recurrent spontaneous abortion.

Recurrent Spontaneous Abortion (RSA) is a significant clinical issue that affects many women, yet its underlying mechanisms remain poorly understood. Recent evidence suggests that immune dysregulation, particularly the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17), may play a critical role in this condition. In this study, we investigate the role of the mTOR signaling pathway in mediating Treg/Th17 cell imbalance in a RSA mouse model established by mating CBA female mice with DBA/2 male mice. The results demonstrate a significant increase in embryo loss rates in the miscarriage group compared to the normal pregnancy group, accompanied by placental damage and an immune imbalance characterized by decreased Treg and increased Th17 cell populations. Furthermore, Enzyme-Linked Immunosorbent (ELISA) assays reveal elevated levels of pro-inflammatory cytokines IL-17, along with reduced anti-inflammatory cytokines TGF-β and IL-10 in the serum of miscarriage mice. To elucidate the role of mTOR, we administered Metformin and Programmed Death-Ligand 1 Fc fusion protein (PD-L1 Fc fusion protein), which significantly improved pregnancy outcomes by restoring the Treg/Th17 ratio and reducing pro-inflammatory cytokine levels. Western blot and qRT-PCR analysis indicated that treatment reduced the expression of mTOR, HIF-1α, ROR-γt, and STAT3, suggesting that both therapies effectively correct Treg/Th17 cell imbalance by inhibiting mTOR signaling. Overall, our findings underscore the importance of mTOR signaling in the Treg/Th17 imbalance associated with RSA, providing new insights for potential therapeutic strategies.