Use of animal models for detecting specific alterations in reproduction.

Conventional tests of reproductive toxicity may fail to detect the effects of some agents altering reproductive functions in the male or female. A valid study of reproductive toxicity must be based on a sound understanding of the underlying reproductive physiology, use of sensitive and precise analytical methods, a powerful experimental design, and evaluation of multiple criteria in both the male and female. Potential sites and mechanisms of action of an agent affecting reproduction were considered together with approaches for tests that might be used. Development of new in vitro tests, based on procedures used for probing reproductive physiology, would be desirable. Procedures for detecting alterations in male reproductive function using animal models were considered in detail. For example, spermatogenesis is a long process and a toxic agent may alter functionality of a testicular cell type several days or weeks before this toxicity is detectable as a change in spermatogenesis. Several weeks or months may pass before a detectable change in semen occurs. Therefore, tests utilizing appropriate animal models should have a duration that is six times the duration of one cycle of the seminiferous epithelium. Evaluations of male reproductive function would be enhanced by including determinations of testicular spermatid reserves, selected simple but precise and meaningful quantitative evaluations of testicular histology, determination of the number of sperm within the distal half of the epididymis, evaluation of the progressive motility and morphology of sperm from the distal end of the epididymis, and measurement of the concentration of follicle stimulating hormone in blood. For rabbits, longitudinal analyses of seminal quality are important.