Co-administration of atorvastatin and piperine disrupts Leydig cell histoarchitecture and compromises sperm structural integrity in male Wistar rats

OBJECTIVE: To investigate the individual and combined effects of atorvastatin and piperine on Leydig cell histoarchitecture and sperm structural integrity in adult male Wistar rats. DESIGN: A randomized controlled experimental animal study. SUBJECTS: Twenty healthy adult male Wistar rats were randomly assigned to four groups (n = 5 per group). EXPOSURE: Animals received oral administration of atorvastatin (8 mg/kg), piperine (10 mg/kg), a combination of atorvastatin and piperine, or vehicle (control) once daily for 28 days. MAIN OUTCOME MEASURES: Leydig cell histoarchitecture was assessed using hematoxylin and eosin, Sudan Black B, and periodic acid-Schiff staining. Epididymal spermatozoa were evaluated for morphological, morphometric, and ultrastructural alterations using light microscopy and scanning electron microscopy. RESULTS: Treatment with atorvastatin and piperine, individually and in combination, significantly reduced Leydig cell number and cluster area while increasing intracellular lipid accumulation and decreasing glycogen content compared with controls (p < 0.05). Sperm abnormalities involving the head, mid-piece, and tail were significantly increased, accompanied by marked reductions in sperm morphometric parameters. Scanning electron microscopy revealed pronounced ultrastructural defects, including acrosomal distortion, plasma membrane constriction, sub-acrosomal swelling, and basal plate abnormalities. The combined treatment group exhibited the most severe histological and sperm ultrastructural alterations. CONCLUSION: Co-administration of atorvastatin and piperine exerts pronounced adverse effects on Leydig cell morphology and sperm structural integrity, suggesting impaired steroidogenesis and spermatogenesis that may compromise male reproductive function. These findings highlight the need for caution regarding the concurrent use of atorvastatin and piperine-containing supplements, particularly among men of reproductive age.