Table 1.

Seminiferous epithelium histopathology following Sertoli cell microtubule disruption

Histopathology Observed	Treatment Inducing Histopathology	Proposed Mechanism	Notes*	References
Seminiferous epithelium sloughing	Colchicine Carbendazim	Destabilization of Sertoli cell stalk by a lack of microtubule structural support	Sloughing may includes the entire circumference of the seminiferous epithelium Reported to be the most sensitive histological endpoint after Sertoli cell microtubule disruption by depolymerising agents Sloughing generally occurs between dissimilar germ cell cohorts with elongating spermatid cohorts being the most sensitive Sloughed material contains fragments of apical Sertoli cell cytoplasm attached by adhesion junctions to intact germ cells Stage dependent: stages III - V are the most resistant to sloughing Rete testis and efferent duct become occluded with sloughed seminiferous epithelium cellular material May result in persistent atrophy of the seminiferous epithelium	30 57 34 4 35 28 29 5 33
Abnormal seminiferous epithelium location of elongating spermatid nuclei	Colchicine Taxol Gamma tubulin overexpression	Inhibition of elongate spermatid movement along Sertoli cell microtubules	Impaired basal movement of elongate spermatids resulting in an their apical location within stage IV - VI seminiferous tubules Impaired apical movement of elongate spermatids during stage VI resulting in step 19 spermatids located in the basal portion of seminiferous epithelium	30 14 15 39
Retained spermatids	Carbendazim 2,5-Hexanedione Gamma tubulin overexpression	Impairment of Sertoli-elongate spermatid junction dynamics followed by Sertoli cell phagocytosis of the elongate spermatid	Retained step 19 spermatids may be present in basal, mid, or apical regions of the seminiferous epithelium Most often observed in stage IX – X seminiferous tubules	33 14 56
Seminiferous epithelium vacuolization	Carbendazim 2,5-Hexanedione MAP7 knockout KATNAL1 knockout	Dilation of Sertoli cell smooth endoplasmic reticulum	Vacuoles are large; one study defined vacuoles as being greater than 16 μm in diameter Vacuoles are observed in the basal compartment of the seminiferous epithelium Treatment-related vacuolization may be observed in only a low percentage of seminiferous tubules	56 47 44 45 33 29 46
Residual body retention	Gamma tubulin overexpression Taxol Colchicine	Failure of residual body movement within the Sertoli cell from an apical to a basal location	Retained residual bodies are identified by their location in the apical seminiferous epithelium of stages IX - XIV seminiferous tubules	14 15 39
Seminiferous epithelium atrophy	Carbendazim 2,5-Hexanedione Colchicine MAP7 knockout	Severe functional Sertoli cell deficit rendering its germ cell “nurse” function inoperable	Represents the “Sertoli cell-only” syndrome Generally a late histopathological finding and progressive in nature Seminiferous tubules are of small diameter, contain few basal spermatogonia, and Sertoli cell cytoplasm fills the tubule lumen May be induced by direct action of the toxic agent on the Sertoli cell such as seminiferous epithelium sloughing or may be secondary to efferent duct blockage	14 47 34 58 28
Enlarged seminiferous tubule lumen	Carbendazim	Rete testis and efferent duct occlusion along with sloughing of seminiferous epithelium	Sloughed seminiferous epithelium occludes the efferent duct leading to back pressure-induced expansion of the seminiferous tubule lumen because of continued seminiferous tubule fluid secretion Occlusion and seminiferous tubule back pressure induce atrophy of the seminiferous epithelium	34 32 44 33

*Seminiferous tubule staging and spermiogenic steps refer to those developed for the rat