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

448 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONtubule diameters). Most technicians take a midline transverse section. However, the testis hasasymmetrical structures (e.g., rete testis) that may be missed by a transverse section.Histopathological evaluations of the testis can determine whether sloughed cells are present inthe tubule lumen, whether the germinal epithelium is degenerating or severely depleted, or whethermultinucleated giant cells are present. Evaluation of the seminiferous tubules should include thepachytene spermatocyte. This cell type has the longest life of the primary spermatocytes with themost RNA and protein synthesis. The pachytene spermatocyte appears to be uniquely susceptibleto toxicants. 73 The rete testis should be examined for dilation due to obstruction or disturbances influid dynamics and for the presence of proliferative lesions and rete testis tumors. Both spontaneousand chemically induced lesions in the rete testis often appear as germ cell degeneration anddepletion. More subtle lesions, such as missing germ cell types or retained spermatids, can reducethe number of sperm being released into the tubule lumen. Such effects may not be detected whenless than adequate methods of tissue preparation have been used. Also, knowledge of the detailedtesticular morphology and spermatogenesis assists in the identification of lesions that may accompanylower treatment levels or result from short-term exposure. 68Several methodologies for qualitative or quantitative assessment of testicular tissue are availablethat can assist in the identification of testicular lesions, including the use of “spermatogenic cyclestaging.” 68,74 To provide high resolution cellular morphologic detail required for spermatogeniccycle staging, semithin (2 µm) sections will have to be produced from testes embedded in glycolmethacrylate resin. A detailed description of spermatogenesis and spermiogenesis required forstaging of spermatogenesis is beyond the scope of this chapter; however, detailed morphologicaldescriptions with light and electron microscopic photographs of these processes are available in anexcellent book by Russell et al. 68Rodent males produce sperm in numbers that greatly exceed the minimum requirements forfertility, particularly as evaluated in reproductive studies that allow multiple matings. 75,76 In somestrains of rats and mice, sperm production can be drastically reduced (by up to 90% or more)without affecting fertility. 77–79 Human male sperm production appears to be much closer to theinfertility threshold; therefore, less severe sperm count reductions may cause human infertility.Negative results in rodent studies that are limited to only fertility and pregnancy outcomes provideinsufficient information to conclude that the test substance poses no reproductive hazard in humans.2. Epididymides, Accessory Sex Glands and PituitaryThe basic morphology of other male reproductive organs (epididymides, accessory sex glands, andpituitary) has been described 80,81 as well as the histopathological alterations that may accompanycertain disease states. 82,83 While detailed descriptions of histology and pathology of these organsare beyond the scope of this chapter, a discussion is presented.The epididymis, a single, long, highly tortuous tube surrounded by connective tissue, has threeportions: the caput (head) located on the anterior pole of the testis, a narrow corpus (body) lyingalong the dorsomedial aspect of the testis, and the cauda (tail) located on the posterior pole of thetestis. The cephalic portion of the epididymis is almost entirely encapsulated in fat. The ductus(vas) deferens is the continuation of the epididymis. The lumen of the vas deferens becomes lesstortuous leading to the prostatic urethra. The secretions of the seminal vesicles, coagulating glands,ampullary glands, dorsal and ventral prostate glands, and bulbourethral glands are added to thesperm in the prostatic and penile urethra to produce semen. Preputial glands do not contribute tothe semen, but rather secrete musklike compounds.A longitudinal section of the epididymis that includes all epididymal segments should beincluded for histopathological examination. During dissection of the epididymis from the testis,care must be taken not to cut the testicular capsule and cause extrusion of the seminiferous tubules,as such damage may disrupt the testicular architecture. Histopathological evaluation of the epididymisshould include information about the caput, corpus, and cauda segments. Presence of debris© 2006 by Taylor & Francis Group, LLC