Testicular histopathology in juvenile rat toxicity studies

Histopathologic interpretation of juvenile toxicity studies is necessarily complicated by the dynamic developmental processes underway within the test subjects. In addition to potentially marked differences in compound metabolism, juvenile animals have vulnerable temporally defined proliferating cell populations compared to their adult counterparts. Pathologists require an understanding of developmental processes and conditions underway during exposure to the compound(s) in a juvenile toxicity study in order to interpret the terminal histopathology accurately. Postnatal testicular development in rats affords an example of how developmental considerations are essential to understanding toxic effects. This review provides an overview of testicular histology and pre- and postnatal testicular development, examples of juvenile rat testicular toxicity from the literature, and considerations for designing juvenile studies for safety assessment of pharmaceutical compounds.