Impact of Age on the Male Reproductive System from the Pathologist's Perspective

Age, and in particular young age, can significantly impact the response to toxicants in animals and can greatly influence the interpretation of tissue changes by the toxicologic pathologist. Although this applies to multiple organ systems, the current review focuses on the male reproductive system. When performing microscopic evaluation of male reproductive organs, the toxicologic pathologist must be aware of the dynamic changes in histomorphology, predominantly driven by timed hormonal alterations, at various life stages. Specific challenges pathologists face are understanding the appearance of male reproductive tissues throughout the neonatal, infantile, and juvenile developmental periods, recognizing when normal looks abnormal during tissue development, defining sexual maturity, and working with high interanimal variability in maturation rate and histologic appearance in developing large laboratory animals, such as nonhuman primates, dogs, and pigs. This review describes postnatal development of the male reproductive system in the rat, demonstrates how assessing toxicity during a defined window of postnatal development in the rat may improve definition of toxicant timing and targets, and discusses challenges associated with the interpretation of toxicity in immature large animal species. The emphasis is on key age-related characteristics that influence the interpretation of tissue changes by the toxicologic pathologist.