Octacosanol ameliorates oligozoospermia in mice through improving cell cycle arrest and regulating testosterone/androgen receptor pathway

Octacosanol (OCT), a nutritional supplement with well-documented biological properties, has not been thoroughly investigated for its impact on oligozoospermia (Oligo) and its molecular mechanisms. In this study, the Oligo mouse model was established by intraperitoneal injection of busulfan. The ICR male mice were randomly divided into Normal, Oligo, and Oligo + OCT (5, 10, or 20 mg/kg) groups, with the highest concentration of OCT showing no organ toxicity. OCT was found to reverse busulfan-induced testicular damage, testicular cytoskeletal impairment and sperm count reduction, while alleviating oxidative stress in Oligo mice. RNA sequencing revealed significant gene expression differences related to ‘nuclear division’ and ‘cell cycle’ between the Oligo and OCT-treated groups. OCT also elevated serum hormone levels in Oligo mice. Western Blot and immunofluorescence confirmed that OCT enhances spermatogenesis through improving cell cycle arrest and regulating testosterone/androgen receptor pathway. OCT may serve as a potential therapeutic agent for male infertility. • Octacosanol enhances spermatogenesis in mice with oligozoospermia. • Octacosanol improves oligozoospermia by promoting cell cycle progression. • Octacosanol regulates the testosterone/androgen receptor pathway in oligozoospermia. • Octacosanol holds promise as a potential medicine for ameliorating male infertility.