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, 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) 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.