Varicocele induces dysbiosis in the epididymis and impairs sperm motility via polyamine synthesis

Varicocele is a common, surgically correctable cause of male subfertility, yet outcomes after varicocelectomy vary and underlying mechanisms remain disputed. We tested whether a varicocele drives dysbiosis in the male reproductive tract and increases bacterial-derived metabolites that impair sperm function. We used a validated rodent surgical model of varicocele and performed tissue bacterial localization. Unilateral varicocele consistently induced bilateral dysbiosis in both the testis and epididymidis and increased bacterial signal in the peritubular and adventitial microenvironments. These findings implicate the microbiome and its associated polyamine metabolome as a potential mechanistic basis for varicocele-associated subfertility and support further work to explore medical therapies to complement surgical varicocele repair.