Tyrosol effectively improves spermatogenesis recovery by S100A9/TLR4/NF-κB pathway in busulfan-induced oligozoospermia mice

Background Oligozoospermia is a prevalent clinical manifestation of male infertility. It has been provided to be bound up with testicular inflammation and oxidative stress. The phenolic compound 2-(4-hydroxyphenyl) ethanol, chemically designated as tyrosol (Tyr), has been widely distributed in multiple botanical sources, such as olive oil, Rhodiola , and other plants. Given its anti-inflammatory and antioxidant properties, Tyr shows potential as a pharmacological candidate for oligozoospermia. This research investigated the phenotype and molecular pathways associated with Tyr in mice. Methods Adult mice were randomly assigned to six groups: a control group, a model group, a hydroxytyrosol (HT) group, and three Tyr groups (10 mg/kg, 30 mg/kg, and 50 mg/kg). All groups except the control group underwent a single does busulfan administration (30 mg/kg) via intraperitoneal injection to induce oligozoospermia. After a two-week observation period, the HT and Tyr groups were treated orally with their respective medications for four weeks. Blood, testes, epididymides, and sperm samples were then collected for further analysis. Results Tyr effectively reversed the mice symptom of oligozoospermia, as demonstrated by increased testis weight, improved sperm concentration, and restored testicular histomorphology. In addition, Tyr normalized serum sex hormone levels and testicular oxidative indices. Moreover, it reduced testicular inflammation by decreasing IL-6 and TNF-α expression, likely through modulation of the S100A9/TLR4/NF-κB pathway. Conclusions Tyr significantly ameliorated oligozoospermia in mice through S100A9/TLR4/NF-κB pathway, suggesting that it may represent a promising therapeutic option for patients with this condition.