Drug transporters in spermatogenesis: A re-evaluation of recent data on P-glycoprotein

Drug transporters are integral membrane proteins expressed by a variety of organs, including the liver, kidney, small intestine and testis, and they are generally known to mediate drug or xenobiotic transport into and out of cells. Previous studies have also reported the presence of several drug transporters at blood-tissue barriers where they are thought to protect organs from harmful agents. In this editorial, we briefly discuss and re-evaluate recent findings that show P-glycoprotein, an efflux pump, to function at the blood-testis barrier. We also put forth a mechanistic model, hoping this information will form a strong basis for future studies

Filamin A: A regulator of blood-testis barrier assembly during post-natal development

Filamins are a family of actin-binding proteins composed of filamin A, B and C. Besides of their ability to induce perpendicular branching of F-actin filaments via their actin binding domains near the N-terminus, filamins can regulate multiple cellular functions because of their unique ability to recruit more than 90 protein binding partners to their primary sequences which are having highly diversified cellular functions. However, this family of proteins has not been examined in the testis until recently. Herein, we highlight recent findings in the field regarding the role of these proteins in cell epithelia, and based on recent data in the testis regarding their role on spermatogenesis, this review provides the basis for future functional studies

Indigenous sharing, collaboration and synchronous learning

Online learning is progressively accepted in Indigenous communities with the realized potential for sharing, collaboration and learning for adults living in remote and isolated communities. This study used a design-based research approach that provided opportunity to integrate the current literature, literacy practitioners\u27 views and community members\u27 self identified literacy needs to generate ten draft guiding principles which guided this study. A collaborative community engagement project was created by the community members in consideration of these principles and presented in three iterations in a synchronous environment which will lead to design-based principles for working with technology and Indigenous communities. This paper examines the framework and approach for this study, provides a short literature review and presents the draft guiding principles drawn from data collected from the stakeholders and from which the project was created

Microtubule affinity-regulating kinase 4 (MARK4) is a component of the ectoplasmic specialization in the rat testis

During the seminiferous epithelial cycle of spermatogenesis, the ectoplasmic specialization (ES, a testis-specific adherens junction, AJ, type) maintains the polarity of elongating/elongated spermatids and confers adhesion to Sertoli cells in the seminiferous epithelium, and known as the apical ES. On the other hand, the ES is also found at the Sertoli-Sertoli cell interface at the blood-testis barrier (BTB) known as basal ES, which together with the tight junction (TJ), maintains Sertoli cell polarity and adhesion, creating a functional barrier that limits paracellular transport of substances across the BTB. However, the apical and basal ES are segregated and restricted to the adluminal compartment and the BTB, respectively. During the transit of preleptotene spermatocytes across the BTB and the release of sperm at spermiation at stage VIII of the seminiferous epithelial cycle, both the apical and basal ES undergo extensive restructuring to facilitate cell movement at these sites. The regulation of these events, in particular their coordination, remains unclear. Studies in other epithelia have shown that the tubulin cytoskeleton is intimately related to cell movement, and MARK [microtubule-associated protein (MAP)/microtubule affinity-regulating kinase] family kinases are crucial regulators of tubulin cytoskeleton stability. Herein MARK4, the predominant member of the MARK protein family in the testis, was shown to be expressed by both Sertoli and germ cells. MARK4 was also detected at the apical and basal ES, displaying highly restrictive spatiotemporal expression at these sites, as well as co-localizing with markers of the apical and basal ES. The expression of MARK4 was found to be stage-specific during the epithelial cycle, structurally associating with α-tubulin and the desmosomal adaptor plakophilin-2, but not with actin-based BTB proteins occludin, β-catenin and Eps8 (epidermal growth factor receptor pathway substrate 8, an actin bundling and barbed end capping protein). More importantly, it was shown that the expression of MARK4 tightly associated with the integrity of the apical ES because a diminished expression of MARK4 associated with apical ES disruption that led to the detachment of elongating/elongated spermatids from the epithelium. These findings thus illustrate that the integrity of apical ES, an actin-based and testis-specific AJ, is dependent not only on the actin filament network, but also on the tubulin-based cytoskeleton

N-WASP Is Required for Structural Integrity of the Blood-Testis Barrier

During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation

Leituras da Orfandade família, Declínio do Pai e Ausência de Lei. uma Abordagem do Universo Ficcional de Rubem Fonseca.

RESUMO Observamos na contemporaneidade que a família assume formas diferentes às que possuía quando foi formulada, no século XVIII. Caracterizada por inúmeras transformações, já não possui uma estrutura tão fixa. A partir das narrativas de Henri, A força humana, Feliz ano novo e O cobrador, de Rubem Fonseca; não deixando de visitar outros trabalhos do escritor, discutiremos e examinaremos as configurações da família contemporânea. Neste sentido, analisaremos as representações da relação do sujeito com as novas estruturas familiares, o declínio da imago paterna e as consequências que essas transformações trazem à subjetividade, bem como as formas pelas quais tais relações são encenadas literariamente pelo escritor brasileir

Environmental contaminants: Is male reproductive health at risk?

Contaminants such as cadmium, bisphenol A, and lead that pollute our environment affect male reproductive function. There is evidence that toxicant exposure adversely affects fertility. Cadmium and b2222isphenol A exert their effects in the testis by perturbing blood-testis barrier function, which in turn affects germ cell adhesion in the seminiferous epithelium because of a disruption of the functional axis between these sites. In essence, cadmium mediated its adverse effects at the blood-testis barrier by disrupting cell adhesion protein complexes, illustrating toxicants dismantle cell junctions in the testis. Herein, we will discuss how environmental toxicants affect reproductive function. We will also examine how these adverse effects on fertility may be mediated in part by adipose tissue and bone. Lastly, we will briefly discuss how toxicant-induced damage may be effectively managed so that fertility can be maintained. It is hoped that this information will offer a new paradigm for future studies

An intracellular trafficking pathway in the seminiferous epithelium regulating spermatogenesis: A biochemical and molecular perspective

During spermatogenesis in adult rat testes, fully developed spermatids (i.e. spermatozoa) at the luminal edge of the seminiferous epithelium undergo spermiation at stage VIII of the seminiferous epithelial cycle. This is manifested by the disruption of the apical ectoplasmic specialization (apical ES) so that spermatozoa can enter the tubule lumen and to complete their maturation in the epididymis. At the same time, the bloodtestis barrier (BTB) located near the basement membrane undergoes extensive restructuring to allow transit of preleptotene spermatocytes so that post-meiotic germ cells complete their development behind the BTB. While spermiation and BTB restructuring take place concurrently at opposite ends of the Sertoli cell epithelium, the biochemical mechanism(s) by which they are coordinated were not known until recently. Studies have shown that fragments of laminin chains are generated from the laminin/integrin protein complex at the apical ES via the action of MMP-2 (matrix metalloprotease-2) at spermiation. These peptides serve as the local autocrine factors to destabilize the BTB. These laminin peptides also exert their effects on hemidesmosome which, in turn, further potentiates BTB restructuring. Thus, a novel apical ES-BTB-hemidesmosome regulatory loop is operating in the seminiferous epithelium to coordinate these two crucial cellular events of spermatogenesis. This functional loop is further assisted by the Par3/Par6-based polarity protein complex in coordination with cytokines and testosterone at the BTB. Herein, we provide a critical review based on the latest findings in the field regarding the regulation of these cellular events. These recent findings also open up a new window for investigators studying bloodtissue barriers