Epimedium polysaccharide alleviates adenine-induced oligoasthenozoospermia in mice by inhibiting ferroptosis and inflammation through TLR4/NF-κB and SLC7A11/GPX4 axis.

This study aimed to investigate the effects and mechanisms of Epimedium polysaccharide (EP) on ferroptosis in oligoasthenozoospermia (OAT) mice through the TLR4/NF-κB and SLC7A11/GPX4 signaling pathways. KM mice were administered adenine via gavage to establish an OAT model, followed by continuous oral or intraperitoneal administration of EP, Ferrostatin-1 (Fer-1) and TAK-242 (a TLR4 inhibitor); testicular spermatogenic function and sperm quality were then evaluated using ELISA tests, HE staining, animal sperm analyzers, and transmission electron microscopy, while ferroptosis and oxidative stress were assessed by Prussian blue staining, biochemical methods, and immunohistochemistry, and inflammation responses and pathway-related proteins were examined through Western Blot, qRT-PCR, and immunofluorescence double staining. The results demonstrated that EP improved spermatogenic function and sperm quality in OAT mice, reduced the extent of ferroptosis and oxidative stress levels, downregulated the expression of TLR4 and NF-κB in OAT mouse testes to thereby decrease inflammation factor levels, and upregulated SLC7A11 and GPX4 to inhibit ferroptosis in testicular cells. Collectively, these findings indicate that the mechanism by which Epimedium polysaccharide improves testicular spermatogenic function in OAT mice may involve regulating TLR4/NF-κB expression and upregulating the SLC7A11/GPX4 pathway, which in turn inhibits ferroptosis and inflammatory responses in testicular cells.