Chapter 11 - Male Genital Tract

Abstract

During the course of drug development, the effects of novel compounds on the reproductive system are examined in specialized reproductive tests. However, these studies are infrequently conducted before the first dose of a novel pharmaceutical to humans. Hence, the only assessment of the male reproductive organs performed prior to the first administration of a novel therapeutic agent to man is histological examination of the male sex organs in conventional toxicity studies in rodent and nonrodent species. For this reason, this assessment should be performed using meticulous techniques. This approach has been agreed in the consensus guidelines from the International Conference on Harmonisation following the studies that showed histopathological examination of the male reproductive organs in the rodent 4-week toxicity study was more sensitive in detecting effects than fertility studies. In mammals the male sex organs comprise the paired testes and the accessory reproductive organs: prostate, seminal vesicles, coagulating glands, ampullary glands, and epididymis. Cytochemical or immunocytochemical demonstration of acid phosphatase has been shown to be a good indicator of the functional integrity of prostatic secretory cells, particularly as acid phosphatase is a major secretory component, which is androgen-dependent in man and laboratory animals. It has been shown that there is a close immunological cross-reactivity of antibody against acid phosphatase from the rat ventral prostate, the canine, and human prostate.