An understanding of form and function is important for examination of the male reproductive tract. A basic understanding of spermatogenesis and hormonal function in the reproductive tract is essential for the pathologists in this evaluation. Gross and histologic reproductive changes need to be distinguished from normal variation and correlated with the reproductive status of the animal. This is especially important when correlating histologic changes with organ weight and other reproductive parameters, such as seminal analysis data. Sexual maturity of animals and tissue handing can impact interpretation. Sexual immaturity of preclinical safety animals can present challenges for accurate identification of compound-related changes. Likewise, proper handling of unfixed reproductive tissues and appropriate selection of a fi xation protocol are important in avoiding artifacts that may interfere with the microscopic evaluation. The histopathology technician needs to recognize testicular landmarks that allow for correct orientation at trimming so the pathologist can assess not only the morphology of seminiferous tubules but also the outfl ow tract. For the most effective evaluation of the male reproductive tract, the testes and epididymides should be examined concurrently. Although the term ``staging'' is often used inappropriately, the pathologist 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 interpretation of potential treatment-related changes in male reproduction.
Cardy RH (1987). Segmental degeneration of the epididymis in aged F344 rats. Vet Pathol24: 361—363.
6.
Chapin RE, White RD, Morgan KT, Bus JS (1984). Studies of lesions induced in the testis and epididymis of F-344 rats by inhaled methyl chloride. Toxicol Appl Pharmacol76: 328—343.
7.
Chellman GJ, Hurtt ME, Bus JS, Working PK (1987). Role of testicular versus epididymal toxicity in the induction of cytotoxic damage in Fischer-344 rat sperm by methyl chloride . Reprod Toxicol1: 25—35.
8.
Clulow J., Jones RC, Hansen LA (1994). Micropuncture and cannulation studies of fl uid composition and transport in the ductuli efferentes testis of the rat: Comparisons with the homologous metanephric proximal tubule. Exp Physiol79: 915—928.
9.
Clulow J., Jones RC, Hansen LA, Man SY (1998). Fluid and electrolyte reabsorption in the ductuli efferentes testis. J Reprod Fertil Suppl53: 1—14.
10.
Comhaire FH , Vermeulen A. (1976). Testosterone concentration in the fluids of seminiferous tubules, the interstitium and the rete testis of the rat. J Endocrinol70: 229—235.
11.
Creasy DM (1997). Evaluation of testicular toxicity in safety evaluation studies: The appropriate use of spermatogenic staging. Toxicol Pathol25: 119—131.
12.
Dirami G., Poulter LW, Cooke BA (1991). Separation and characterization of Leydig cells and macrophages from rat testes. J Endocrinol130: 357—365.
13.
Dym M. (1976). The mammalian rete testis—A morphological examination. Anat Rec186: 493—534.
14.
Ellis LC, Buhrley LEJ, Hargrove JL (1978). Species differences in contractility of seminiferous tubules and tunica albuginea as related to sperm transport through the testis . Arch Androl1: 139—146.
15.
Ellis LC, Groesbeck MD, Farr CH, Tesi RJ ( 1981). Contractility of seminiferous tubules as related to sperm transport in the male. Arch Androl6: 283—294.
16.
Fawcett DW, Neaves WB, Flores MN (1973). Comparative observations on intertubular lymphatics and the organization of the interstitial tissue of the mammalian testis. Biol Reprod9: 500—532.
17.
Filippini A. , Tripiciano A., Peluso C., Morena AR, Stefanini ZM, Palombi F. (2000). ECE-1 is cyclically expressed in Sertoli cells and mediates the spatiotemporal control of tubular contractility . Andrologia32: 61.
18.
Flickinger CJ, Howards SS, English HF (1978). Ultrastructural differences in efferent ducts and several regions of the epididymis of the hamster. Am J Anat152: 557—585.
19.
Foley GL, Bassily N., Hess RA ( 1995). Intratubular spermatic granulomas of the canine efferent ductules. Toxicol Pathol23: 731— 734.
20.
Forssmann WG , Ito S., Weihe E., Aoki A., Dym M. (1977). An improved perfusion fixation method for the testis. AnatRec188: 307 — 314.
21.
Goyal HO, Hrudka F. (1980). The resorptive activity in the bull efferent ductules—A morphological and experimental study. Andrologia12: 401 — 404.
22.
Goyal HO, Williams CS (1988). The ductuli efferentes of the goat: A morphological study. Anat Rec220: 58—67.
23.
Guttroff RF , Cooke PS, Hess RA (1992). Blind-ending tubules and branching patterns of the rat ductuli efferentes . Anat Rec232: 423 — 431.
24.
Harleman JH , Nolte T. (1997). Testicular toxicity: regulatory guidelines—The end of formaldehyde fi xation?Toxicol Pathol25: 414 — 417.
25.
Hart BL ( 1970). Reproductive system. In: The Beagle as an Experimental Dog, Andersen AC, Good LS (eds). Iowa State University Press, Ames, pp 296—312.
26.
Hemeida NA, Sack WO, McEntee K. (1978). Ductuli efferentes in the epididymis of boar, goat, ram, bull, and stallion. Am J Vet Res39: 1892—1900.
27.
Hess RA (1990). Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: Light microscopic observations of perfusion-fixed and plastic-embedded testes . Biol Reprod43: 525—542.
28.
Hess RA (1998). Effects of environmental toxicants on the efferent ducts, epididymis and fertility. J Reprod Fertil Suppl53: 247—259.
29.
Hess RA, Gist DH, Bunick D., Lubahn DB, Farrell A., B ahr J., Cooke PS, Greene GL (1997). Estrogen receptor (alpha and beta) expression in the excurrent ducts of the adult male rat reproductive tract. J Androl18: 602—611.
30.
Hess RA, Moore BJ (1993). Histological methods for evaluation of the testis. MethodsToxicol3A: 52—85.
31.
Hess RA, Moore BJ, Forrer J., Linder RE, Abuel-Atta AA (1991). The fungicide benomyl (methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate) causes testicular dysfunction by inducing the sloughing of germ cells and occlusion of efferent ductules. Fundam Appl Toxicol17: 733—745.
32.
Hess RA, Schaeffer DJ, Eroschenko VP, and Keen JE (1990). Frequency of the stages in the cycle of the seminiferous epithelium in the rat. Biol Reprod43: 517—524.
33.
Hinton BT, Turner TT (1988). Is the epididymis a kidney analogue?News Physiol Sci3: 28—31.
34.
Hohlbrugger G. (1980). A micropuncture study of transepithelial water reabsorption in rat ductuli efferentes. Fertil Steril34: 50 — 54.
35.
Hoyt JA, Fisher LF, Hoffman WP, Swisher DK, Seyler DE (1994). Utilization of a short-term male reproductive toxicity study design to examine effects of alpha-chlorohydrin (3-chloro-1,2-propanediol) . Reprod Toxicol8: 237—250.
36.
Hutson JC (1992). Development of cytoplasmic digitations between Leydig cells and testicular macrophages of the rat. Cell Tissue Res267: 385—389.
37.
Ilio KY, Hess RA ( 1994). Structure and function of the ductuli efferentes: A review . Microsc Res Tech29: 432—467.
38.
James RW, Heywood R. (1979). Age-related variations in the testes and prostate of Beagle dogs. Toxicology12: 273—279.
39.
Jonté G., Holstein AF (1987). On the morphology of the transitional zones from the rete testis into the ductuli efferentes and from the ductuli efferentes into the ductus epididymidis: Investigations on the human testis and epididymis . Andrologia19: 398—412.
40.
Klinefelter GR , Hess RA (1998). Toxicology of the male excurrent ducts and accessory sex glands. In: Reproductive and Developmental Toxicology, Korach KS (ed). Marcel Dekker, New York , pp 553—591.
41.
Klinefelter GR, Roberts NL, Suarez JD (1992). Direct effects of ethane dimethanesulphonate on epididymal function in adult rats: An in vitro demonstration . J Androl13: 409—421.
42.
Larsen WJ (1997). Development of the urogenital system. In: Human Embryology, 2nd ed, Larsen WJ (ed). Churchill Livingstone , New York, pp 261—309.
43.
Liu X., Temple-Smith PD, Risbridger GP (1993). Acute effects of ethane dimethane sulfonate (EDS) on the structure of the cauda epididymidis in the rat: Selective destruction of clear cells in the proximal cauda region. Reprod Fertil Dev5: 295—306.
44.
Maddocks S. , Sharpe RM (1989). The route of secretion of inhibin from the rat testis. J Endocrinol120: R5—R8.
45.
Maekawa M., Kamimura K., Nagano T. (1996). Peritubular myoid cells in the testis: Their structure and function. Arch Histol Cytol59: 1—13.
46.
Mawdesley-Thomas LE, Urwin C. (1967). Epithelial hyperplasia of the epididymis in the beagle. Vet Rec18: 356—357.
47.
McEntee K. (1990). Efferent ductules, epididymis, and deferent duct . In: Reproductive Pathology of Domestic Mammals, McEntee K (ed). Academic Press, San Diego, pp 307—332.
48.
McEntee K. (1990). Scrotum and testis: Anatomy and congenital anomalies . In: Reproductive Pathology of Domestic Mammals, McEntee K (ed). Academic Press, San Diego, pp 224 — 251.
49.
Mitchinson MJ , Sherman KP, Stainer-Smith AM (1975). Brown patches in the epididymis. J Pathol115: 57—62.
50.
Miyake K., Yamamoto M., Narita H., Hashimoto J., Mitsuya H. (1986). Evidence for contractility of the human seminiferous tubule confirmed by its response to noradrenaline and acetylcholine. Fertil Steril46: 734—737.
51.
Nakai M., Moore BJ, Hess RA ( 1993). Epithelial reorganization and irregular growth following carbendazim-induced injury of the efferent ductules of the rat testis. Anat Rec235: 51—60.
52.
Newcombe N., Clulow J., Man SY, Jones RC (2000). pH and bicarbonate in the ductuli efferentes testis of the rat. Int J Androl23: 46—50.
53.
Nistal M., Iniguez L., Paniagua R., Regadera J. (1986). Diverticula of the ductus epididymis in men. J Urol136: 1224—1227.
54.
Reid BL, Cleland KW (1957). The structure and function of the epididymis. I The histology of the rat epididymis. AustJ Zool5: 223—254.
55.
Robaire B., Hermo L. (1988). Efferent ducts, epididymis, and vas deferens: Structure, functions, and their regulation. In: The Physiology of Reproduction, Knobil E, Neill J (eds). Raven Press, New York, pp 999—1080.
56.
Russell LD, Ettlin RA, Sinha Hikim Ap, Clegg ED (eds) (1990). Histological and Histopathological Evaluation of the Testis. Cache River Press, Clearwater, Forida.
57.
Serre V., Robaire B. (1998). Segment-specifi cmorphological changes in aging Brown Norway rat epididymis. Biol Reprod58: 497— 513.
58.
Setchell BP (1970). The secretion of fl uid by the testes of rats, rams and goats with some observations on the effect of age, cryptorchidism and hypophysectomy. J Reprod Fertil23: 79—85.
59.
Setchell BP , Pollanen P., Zupp JL (1988). Development of the blood-testis barrier and changes in vascular permeability at puberty in rats. Int J Androl11: 225—233.
60.
Sharp SC, Batt MA, Lennington WJ (1994). Epididymal cribriform hyperplasia: A variant of normal epididymal histology. Arch Pathol Lab Med118: 1020 — 1022.
61.
Sharpe RM (1994). Regulation of spermatogenesis. In: The Physiology of Reproduction, Knobil E, Neill J (eds). Raven Press, New York, pp 1364—1434.
62.
Taha MA, Noakes DE, Allen WE (1981). Some aspects of reproductive function in the male beagle at puberty. J Small Anim Pract22: 663—667.
63.
Takayama S. , Akaike M., Kawashima K., Takahashi M., Kurokawa K. (1995). A collaborative study in Japan on optimal treatment period and parameters for detection of male fertility disorders induced by drugs in rats. J Am Coll Toxicol14: 266—292.
64.
Wright JR Jr (1987). Atrophy, testis, rat. In: Genital System, Jones TC, Mohr U, Hunt RD (eds). Spring-Verlag, Berlin , pp 218—225.
65.
Yuan YD, Kennedy AH, Ochoa R. (1994). Testicular toxicity of theophylline in rats. Toxicol Pathol22: 655 (abstract).
