Mechanisms of spermiogenesis and spermiation and how they are disturbed

Abstract

Haploid round spermatids undergo a remarkable transformation during spermiogenesis. The nucleus polarizes to one side of the cell as the nucleus condenses and elongates, and the microtubule-based manchette sculpts the nucleus into its species-specific head shape. The assembly of the central component of the sperm flagellum, known as the axoneme, begins early in spermiogenesis, and is followed by the assembly of secondary structures needed for normal flagella. The final remodelling of the mature elongated spermatid occurs during spermiation, when the spermatids line up along the luminal edge, shed their residual cytoplasm and are ultimately released into the lumen. Defects in spermiogenesis and spermiation are manifested as low sperm number, abnormal sperm morphology and poor motility and are commonly observed during reproductive toxicant administration, as well as in genetically modified mouse models of male infertility. This chapter summarizes the major physiological processes and the most commonly observed defects in spermiogenesis and spermiation, to aid in the diagnosis of the potential mechanisms that could be perturbed by experimental manipulation such as reproductive toxicant administration. Signature LesionThere are a number of signature lesions that could indicate a disturbance in spermiogenesis or spermiation. These would include misshapen heads and/or tails of elongating/elongated spermatids. Multinucleated round spermatids may reflect disturbances in spermiogenesis, but could also reflect altered Sertoli cell function. Disruption of spermiation could present itself as spermatid retention at the lumen of post stage VIII tubules, failure of elongated spermatids to ascend to the lumen of stage VII/ VIII tubules, or phagocytosis of mature spermatids at the base of tubules in stages VII through to approximately XII (in mice) or XIV (in rats). The changes might occur in isolation or in combination with one another.

Regulation of blood–testis barrier by actin binding proteins and protein kinases

“…On the other hand, MTs serve as the rails (or tracks) in Sertoli cells for germ cell transport (most notably spermatids), phagosome transport, as well as for intracellular transport involved in organelle positioning, cell shape, cell polarity, cell division and endocytic vesicle-mediated trafficking (for reviews, see (Lie, et al 2010c, O’[Donnell and O’Bryan 2014, O’Donnell 2014, Tang, et al 2013, Tang, et al 2015b, Vogl, et al 2008)). MTs are also polarized structures in Sertoli cells with the fast growing plus (+) end and the slow growing minus (−) ends located near the basement membrane in the basal compartment and near the tubule lumen in the apical compartment, respectively.…”

“…MT dynamics are also regulated by a number of MT binding proteins, yet few studies are found in the literature that investigate the role of these MT binding proteins on MT dynamics in the testis (Table 2) (for reviews, see (O’Donnell and O’Bryan 2014, Tang, et al 2013, Tang, et al 2015b)). Nonetheless, both cytoskeletal filaments undergo extensive re-organization involving polymerization (i.e., nucleation), depolymerization, stabilization, bundling, capping, branching and severing/cleavage so that their configuration and/or organization can be rapidly altered in Sertoli cells in response to changes of the epithelial cycle, similar to other mammalian and non-mammalian cells (Arous and Halban 2015, Hausott and Klimaschewski 2015, Lie, et al 2010c, O’Donnell, et al 2011, O’Donnell and O’Bryan 2014, O’Donnell 2014, Tang, et al 2015b, Zheng and Iglesias 2013). Furthermore, studies have shown that the actin- and MT-based cytoskeletons are working in concert to modulate multiple mammalian cell functions including spermatogenesis in the testis (for reviews, see (Coles and Bradke 2015, O’Donnell, et al 2011, O’Donnell 2014, Poulter and Thomas 2015, Schappi, et al 2014, Tang, et al 2015b)).…”

“…Nonetheless, both cytoskeletal filaments undergo extensive re-organization involving polymerization (i.e., nucleation), depolymerization, stabilization, bundling, capping, branching and severing/cleavage so that their configuration and/or organization can be rapidly altered in Sertoli cells in response to changes of the epithelial cycle, similar to other mammalian and non-mammalian cells (Arous and Halban 2015, Hausott and Klimaschewski 2015, Lie, et al 2010c, O’Donnell, et al 2011, O’Donnell and O’Bryan 2014, O’Donnell 2014, Tang, et al 2015b, Zheng and Iglesias 2013). Furthermore, studies have shown that the actin- and MT-based cytoskeletons are working in concert to modulate multiple mammalian cell functions including spermatogenesis in the testis (for reviews, see (Coles and Bradke 2015, O’Donnell, et al 2011, O’Donnell 2014, Poulter and Thomas 2015, Schappi, et al 2014, Tang, et al 2015b)). For instance, a recent report has shown that a knockdown of EB1 [end binding protein 1, a member of the growing +TIPs (plus (+) end tracking proteins) (for reviews, see (Akhmanova and Steinmetz 2010, Jiang and Akhmanova 2011))] which is known to promote MT stabilization and to serve as an adaptor to recruit other +TIP proteins to the growing MT plus ends (Tamura and Draviam 2012), not only affects the organization of MTs but also actin microfilaments in Sertoli cells (Tang, et al 2015a) (Table 2).…”

“…Since the involvement of MT in BTB function has recently been reviewed (for reviews, see (O’Donnell 2014, Tang, et al 2015b)), we focus our discussion on the actin-based cytoskeleton herein since there are more recent published findings on this subject that have not been reviewed. We also provide a model herein (Figure 2) which can serve as a helpful guide to investigators in the field.…”

Pesticide Exposures Induce Male-Mediated Reproductive Toxicity: A Review

“…Histone-to-protamine chromatin remodelling process happens perfectly in the presence of a master regulator, namely chromodomain helicase DNA binding protein 5 (Chd5) throughout spermiogenesis . Spermiogenesis is a process to produce matured spermatozoa which able to move from haploid round spermatids by completing a remarkable series of events (O'Donnell, 2014). When making a comparison, it is noted that nuclei of sperm wild-type sperm with larger amounts of protamine contents are more resistant to chemical disruption (Cho et al, 2001).…”