γ-Tubulin Overexpression in Sertoli Cells In Vivo. II: Retention of Spermatids, Residual Bodies, and Germ Cell Apoptosis1

Abstract

The degree of germ cell dependence on Sertoli cell-mediated activities has been a subject of considerable attention. Sertoli cell secretory pathways have been extensively studied both in an effort to understand their normal physiologic roles and as targets for pharmacologic and toxicant activity. To determine the degree to which normal spermatogenesis depends on key functions of the Sertoli cell microtubule network, adenoviral vectors that overexpress the microtubule nucleating protein, gamma-tubulin, were delivered to Sertoli cells in vivo. gamma-Tubulin overexpression disrupts the Sertoli cell microtubule network (as described in the companion article); leads to gross disorganization of the seminiferous epithelium, inducing retention of spermatids and residual bodies; and causes germ cell apoptosis. These data are consistent with earlier studies in which toxicants and pharmacologic agents were used to disrupt microtubule networks. These data confirm that Sertoli cell microtubule networks play an important role in maintaining the organization of the seminiferous epithelium and that in the absence of an intact Sertoli cell microtubule network, germ cell viability is impaired.

Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation

“…Spermiation involves a variety of cell adhesion molecules and requires the integrity of the SC cytoskeleton (Russell et al 1989, Fleming et al 2003, Lee & Cheng 2004. In this context, it is noteworthy that inactivating RXRB specifically in SC i) decreases the expression of genes encoding proteins associated with actin microfilaments (i.e.…”

Testicular histopathology associated with disruption of the Sertoli cell cytoskeleton

“…9,10 This pattern also allows the Sertoli cell microtubules to function as a platform upon which microtubule motors attach to specialized Sertoli-spermatid adhesion junctions (ectoplasmic specializations) and move elongating spermatids within the seminiferous epithelium along the Sertoli cell apicobasal axis. 11,12 Other functions ascribed to Sertoli cell microtubules include secretion of seminiferous tubule fluid, 13 intracellular movement of germ cell residual bodies from the apical to basal Sertoli cell subcellular compartments, 14,15 and release of mature spermatids from the seminiferous epithelium (spermiation). 14,15 Sertoli cell actin-based microfilaments are abundant at 2 specialized testis-specific intercellular junctions.…”

“…11,12 Other functions ascribed to Sertoli cell microtubules include secretion of seminiferous tubule fluid, 13 intracellular movement of germ cell residual bodies from the apical to basal Sertoli cell subcellular compartments, 14,15 and release of mature spermatids from the seminiferous epithelium (spermiation). 14,15 Sertoli cell actin-based microfilaments are abundant at 2 specialized testis-specific intercellular junctions. One of these junctions is the ectoplasmic specialization, 12,16 and the other is the tubulobulbar complex 17,18 (also see Cheng, this issue).…”

“…Agents that depolymerize or stabilize Sertoli cell microtubules may produce the histopathological observation of abnormal elongate spermatid nuclear position. While abnormal spermatid location has often been analyzed qualitatively, Fleming et al 14 quantified this endpoint by dividing the seminiferous epithelium of selected stages into apical and basal sectors and counting elongate spermatid nuclei within the sectors. Taxol is a plant-derived toxin that directly binds b-tubulin and stabilizes microtubules leading to abnormal microtubule dynamics and an excess of microtubules within cells.…”

“…41 In the rat, residual body retention is a histological observation of residual bodies within the apical seminiferous epithelium in stage X-XIV seminiferous tubules. 14,15 Retained residual bodies have been observed after testicular exposure to agents that alter Sertoli cell microtubule polymerization dynamics, including colchicine, 39 g-tubulin overexpression, 14 and taxol. 15 The mechanism for this effect is unclear but is hypothesized to be disruption of microtubule-based Sertoli cell transport of residual bodies to the basal Sertoli cell cytoplasm.…”