Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging.

Toxicology of the male reproductive system has received increased interest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reproduction and fertility have emphasized the importance of detailed histopathological examination of the testes as a sensitive method for detecting disturbances in spermatogenesis. Unfortunately this has been accompanied by a general confusion regarding a practical approach to undertaking such a detailed examination, particularly in respect to the use of spermatogenic or tubular staging to identify subtle disturbances in spermatogenesis. The ability to identify tubular stages of the spermatogenic cycle in sections of testis plus a good understanding of the spermatogenic process and its dynamics are essential in order to carry out a sensitive of testicular histopathology and to interpret the changes seen. A rational approach is required initially to detect and subsequently to characterize toxic effects to the male reproductive system. It is important that a distinction is made between these two objectives since different study designs are required and different methodology may be employed to produce the type of information or data required.