Testicular histopathology associated with disruption of the Sertoli cell cytoskeleton

Johnson, Kamin J.

doi:10.4161/21565562.2014.979106

Cited by 77 publications

(57 citation statements)

References 57 publications

(88 reference statements)

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“…This animal model, similar to other drug models such as treatment of rats with environmental toxicant cadmium or other toxicants (e.g., carbendazim, 2,5-hexanedione, colchicine), is known to induce germ cell exfoliation from the testis. [55][56][57] It was noted that while spermatids near the tubule lumen at stage VI to early VIII were depleting from the epithelium, analogous to the release of sperm at spermiation, many step 19 spermatids remained entrapped deep inside the epithelium. 8 These step 19 spermatids were consistently found in the epithelium of stages IX, X, XI and XII tubules, until they were eventually engulfed and degraded by Sertoli cells.…”

Section: The Adjudin Modelmentioning

confidence: 99%

Transport of germ cells across the seminiferous epithelium during spermatogenesis—the involvement of both actin- and microtubule-based cytoskeletons

et al. 2016

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The transport of germ cells from the base of the seminiferous epithelium toward the luminal edge of the tubule lumen in the adluminal compartment during the epithelial cycle is an essential cellular event to support spermatogenesis. Thus, fully developed elongated spermatids (i.e., spermatozoa) can be released at spermiation in late stage VIII in rodents versus late stage II in humans. Earlier studies to examine the molecular mechanism(s) that support germ cell transport, most notably the transport of preleptotene spermatocytes across the blood-testis barrier (BTB), and the transport of elongating spermatids across the adluminal compartment during spermiogenesis, is focused on the adhesion protein complexes at the cell-cell interface. It is generally accepted that cell junctions at the Sertoli cell-cell interface at the BTB, including the actin-based tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific adherens junction) and gap junction (GJ), as well as the intermediate filament-based desmosome undergo constant remodeling to accommodate the transport of preleptotene spermatocytes across the barrier. On the other hand, similar junction dynamics (i.e., disassembly, reassembly and stabilization/maintenance) take place at the Sertoli-spermatid interface. Emerging evidence has shown that junction dynamics at the Sertoli cell-cell vs. Sertoli-germ cell interface are supported by the 2 intriguingly coordinated cytoskeletons, namely the F-actin-and microtubule (MT)-based cytoskeletons. Herein, we provide a brief summary and critically evaluate the recent findings. We also provide an updated hypothetical concept regarding germ cell transport in the testis utilizing the MT-conferred tracks and the MT-specific motor proteins. Furthermore, this cellular event is also supported by the F-actin-based cytoskeleton.

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Section: The Adjudin Modelmentioning

confidence: 99%

Transport of germ cells across the seminiferous epithelium during spermatogenesis—the involvement of both actin- and microtubule-based cytoskeletons

et al. 2016

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“…1d), Eps8 (an actin barbed end capping and bundling protein) [13, 17, 24], and palladin (an actin-bundling protein) [25]. In both animal models, namely, the adjudin and the formin 1 knockdown model, step 19 spermatids are persistently found in the seminiferous epithelium that are trapped near the base of the epithelium in stage IX–XII tubules until they are eliminated by the Sertoli cell through lysosomal degradation, sometimes through the appearance of multinucleated round and/or spermatocytes [13, 15, 16], as noted in other toxicant-induced aspermatogenesis models [26–29]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

Wen

Tang

et al. 2018

Methods in Molecular Biology

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The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17–20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons. We focus on the role of two actin nucleation protein complexes, namely, the Arp2/3 (actin-related protein 2/3) complex and formin 1 (or the formin 1/spire 1 complex) known to induce actin nucleation, respectively, by conferring plasticity to actin cytoskeleton. We also focus on the MT plus (+)-end tracking protein (+TIP) EB1 (end-binding protein 1) which is known to confer MT stabilization. Furthermore, we discuss in particular how the interactions of these proteins modulate BTB dynamics during spermatogenesis. These findings also yield a novel hypothetical concept regarding the molecular mechanism that modulates BTB function.

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“…Studies using environmental toxicants (e.g., 2, 5-hexanedione, carbendazim) have also demonstrated that the MT-based cytoskeleton in Sertoli cells is the primary target of these toxicants. In short, 2,5-hexanedione and/or carbendazim induce germ cell maturation arrest, disruption of fluid secretion by Sertoli cells leading to tubule atrophy, failure in spermatid transport, and an increase in cell apoptosis, thereby causing progressive germ cell exfoliation (for reviews, see (Boekelheide, et al 2003, Johnson 2014)). Other studies have also illustrated the disruption of actin microfilaments by cadmium and glycerol leads to TJ fibrils truncation, defragmentation of actin microfilaments, and BTB disruption, coinciding with germ cell exfoliation (Hew, et al 1993, Wiebe, et al 2000) since many of the adhesion protein complexes at the BTB utilize actin filaments for attachment (for a review, see (Cheng and Mruk 2002)).…”

Section: Cytoskeletons Of the Btbmentioning

confidence: 99%

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

Li¹,

Tang²,

Cheng³

2016

Reproduction

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The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases.

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Testicular histopathology associated with disruption of the Sertoli cell cytoskeleton

Cited by 77 publications

References 57 publications

Transport of germ cells across the seminiferous epithelium during spermatogenesis—the involvement of both actin- and microtubule-based cytoskeletons

Transport of germ cells across the seminiferous epithelium during spermatogenesis—the involvement of both actin- and microtubule-based cytoskeletons

Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

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

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