An understanding of form and function is important for examination of the m
ale reproductive tract. A basic understanding of spermatogenesis and hormon
al function in the reproductive tract is essential for the pathologists in
this evaluation. Gross and histologic reproductive changes need to be disti
nguished from normal variation and correlated with the reproductive status
of the animal. This is especially important when correlating histologic cha
nges with organ weight and other reproductive parameters. such as seminal a
nalysis data. Sexual maturity of animals and tissue handing can impact inte
rpretation. Sexual immaturity of preclinical safety animals can present cha
llenges for accurate identification of compound-related changes. Likewise,
proper handling of unfixed reproductive tissues and appropriate selection o
f a fixation protocol are important in avoiding artifacts that may interfer
e with the microscopic evaluation. The histopathology technician needs to r
ecognize testicular landmarks that allow for correct orientation at trimmin
g so the pathologist can assess nor only the morphology of seminiferous tub
ules but also the outflow tract. For the most effective evaluation of the m
ale reproductive tract, the testes and epididymides should be examined conc
urrently. Although the term "staging" is often used inappropriately, the pa
thologist should review testicular tissues in a "stage-aware" manner. This
article reviews gross and histologic changes of the male reproductive tract
as well as tissue orientation and fixation to assist in accurate interpret
ation of potential treatment-related changes in male reproduction.