Pathology of the Male and Female Reproductive System and Mammary Gland

Abstract

Test article–related effects on the reproductive system can have a profound effect on pharmaceutical development. The reproductive system has several unique features that differ from other organ systems, including complex hormonal regulation; age-related changes such as puberty and reproductive senescence; sex-specific characteristics such as spermatogenesis in the male and cyclicity in the female; pronounced species differences; and evaluation occurring in the context of both repeated-dose general toxicology studies and stand-alone developmental and reproductive toxicology (DART) studies. This requires a broad integration of toxicology and pathology with knowledge of reproductive endocrinology, development, and comparative biology. This chapter reviews the pathology of the male and female reproductive system, including the mammary gland in females. In males, the functional anatomy and physiology are reviewed. Key issues for toxicologists, including stage-aware evaluation of spermatogenesis and sexual maturity, are discussed. Background lesions for common laboratory animals, common test article–related lesions and reversibility, ancillary testing, and issues of relevance to humans are covered. The female reproductive system and mammary gland are covered in a similar format with important issues for toxicologists including reproductive senescence and sexual maturity.