Electron micrographs of testis pathology associated with bortezomib treatment. Lower panel shows electron micrographs of testicular sections of mice sacrificed 2 days (D), 45 days (E), and 6 months (F) after the last bortezomib injection. Upper panels (A-C) display the respective untreated controls. Magnification of all micrographs is 3000×. Damage includes the premature release of round spermatids (D, arrows) and elongated spermatids (open triangle) as here illustrated in mice sacrificed 2 days after the last bortezomib injection. In mice sacrificed 45 days post-treatment (E), the germ cell loss had reduced the height of the seminiferous epithelium into a single cell layer (arrows) with malformed nuclei (open triangle). In mice killed 6 months after the last bortezomib injection (F), vacuolization of elongated spermatids (open triangles), impairment of the acrosome formation (arrows), and degeneration of germ cells were evident.