A B S T R A C T Article type: Original Objective(s): Research on the male gonadotoxic effects of olanzapine (OLZ) and the potential protective role of vitamin E (Vit E) remains limited. This investigation aimed to assess the toxic impact of OLZ on the testes’ integrity and the protective role of dietary Vit E. Materials and Methods: In this experimental study, twenty-eight rats were divided into four groups: a control group, a group administered 5 mg/kg of OLZ orally, a group receiving both OLZ and 100 mg/kg of Vit E, and a group treated with Vit E alone. We assessed testes dimensions, structural alterations, serum concentrations of testosterone and prolactin, sperm parameters, oxidative stress, and apoptosis. Additionally, the expression levels of microRNA (miR)-122 and miR-202-5p were quantified. Results: Administration of OLZ resulted in significant structural damages to the testes characterized by apoptosis, cellular stress, and disruption of miR-122 and miR-202-5p expression. Otherwise, Vit E restores the histological structure, apoptosis, and sperm quality affected by OLZ. Notably, hormonal profiles and indices of cellular stress showed significant improvement in rats receiving a combination of Vit E and OLZ. Furthermore, the expressions of miR-122 and miR-202-5p were normalized in the OLZ+Vit E treated group. Conclusion: This study highlights the protective role of dietary Vit E against OLZ-induced testicular toxicity by enhancing testicular histo-architecture, reducing stress markers, and modulating of microRNA expression
