Effect of bortezomib on testicular histology. Microphotographs showing testicular histology in a 35 day old untreated control mouse (A, B), and in mice sacrificed 2 days (C, D), 45 days (E, F), or 6 months (G, H) after the last bortezomib injection. In bortezomib-treated animals (C-H), spermatogenesis was variably impaired with tubules ranging from Sertoli cells only (arrows) to various degrees of hypospermatogenesis (mixed atrophy) and release of premature germ cells into the lumen (D, F, H, triangles). Loss of germ cells was related to shrinkage of seminiferous epithelium with enlarged interstitial spaces (C-H, stars). Images were captured at 4× (A, E, C, G; bars 500 μm) or 60× (B, F, D, H; bars 50 μm) magnification. Corresponding images are displayed side-by-side.