A Practical Approach, Second Edition=Ronald D. Ho.pdf

446 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONE. Male Reproductive Organ WeightMale reproductive organ weights are collected for the testes, epididymides, seminal vesicles (withcoagulating glands), and prostate. The pituitary gland is also routinely harvested and weighed. Theorgan weight values should be reported as both absolute weights and relative weights (organ weightto body weight ratio). Organ weight to brain weight data is often reported because the weight ofthe brain in the adult rat usually remains quite stable. 56 Mean normal testis weight varies onlyslightly within a given experimental species, 57,58 suggesting that absolute testis weight should be agood indicator of testicular injury. However, reduction in testis weight is often detected only attreatment levels greater than those required to produce significant effects on other gonadal parameters.59–61There can be a temporal delay between testicular cell death and testicular weight change. Whilecell death would be expected to reduce testicular weight, testicular edema and inflammation, cellularinfiltration, and/or Leydig cell hyperplasia may actually increase testicular weight. Sloughed deadgerminal epithelium cells can cause a blockage of the efferent ducts, causing increased testis weightas a result of fluid accumulation. 62,63 While testis weight may not be a good indicator for certainadverse testicular effects, a significant alteration in testicular weight should be considered an adversemale reproductive effect.Epididymal and cauda epididymal weights are often required in reproductive studies, especiallywhen sperm parameters are evaluated. Because sperm are within the epididymis and thereforecontributes to its weight, reductions in sperm production can alter the epididymal weight. Thepresence of lesions such as sperm granulomas or leukocytic infiltration (inflammation) in theepididymal epithelium can also affect the epididymal weight.Because the seminal vesicle and prostate are androgen-dependent organs, weight changes inthese organs may reflect alterations in endocrine status or testicular function. The seminal vesiclesand prostate can respond differently to a test substance; therefore, information will be improved ifthe weights were collected separately (with and/or without their secretory fluids). Differential lossof secretory fluids prior to weighing can cause artifactual organ weights or increased variation inorgan weight values.Pituitary weight can provide information on the reproductive status of an animal. However, thepituitary contains many other cell types that are responsible for the regulation of numerous physiologicfunctions unrelated to reproduction. Therefore, alterations in pituitary weight do not necessarilyreflect altered reproductive function. Selective histological stains may be used to confirmalterations in regions of the pituitary associated with reproductive functions. If the pituitary weightchange can be associated with changes in reproductive function of the pituitary, then the pituitaryweight change should be considered an adverse reproductive effect.Significant changes in male reproductive organ weights (absolute and/or relative) should beconsidered an adverse male reproductive effect. However, lack of reproductive organ weight effectsshould not be used to negate significant changes in other reproductive endpoints.F. Histopathological Evaluation of the Male Reproductive OrgansHistopathological evaluations of the male reproductive organs have a prominent role in toxicityassessment. Detailed descriptions of the histology and pathology of the male reproductive systemare beyond the scope of this chapter; however, brief discussions of the organs comprising the malereproductive system are presented. Routinely evaluated male reproductive organs include the testes,epididymides, prostate, seminal vesicles, coagulating glands, and pituitary. Histopathological evaluationscan be especially useful by (1) providing location (including target cells) and severity ofthe lesion, (2) providing comparative data from a variety of reproductive study designs, (3) providinga relatively sensitive indicator of damage in short-term dosing studies, and (4) describing recoveryafter the cessation of treatment. When similar targets or mechanisms exist in humans, the basis for© 2006 by Taylor & Francis Group, LLC