scholarly journals Molecular mechanisms by which hormones and cytokines regulate cell junction dynamics in the testis

2009 ◽  
Vol 43 (2) ◽  
pp. 43-51 ◽  
Author(s):  
Wing-Yee Lui ◽  
Will M Lee
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cellular Functions ◽  
Regulatory Effects ◽  
Factor Α

Hormones and cytokines are known to regulate cellular functions in all tissues including testis. These two groups of biomolecules exert a broad spectrum of effects on various aspects of spermatogenesis. Among them, one of the regulatory effects on spermatogenesis is to modulate cell junction restructuring between Sertoli cells and between Sertoli and germ cells in the seminiferous epithelium. The restructuring of cell junctions is crucial to enable the migration of germ cells along the seminiferous epithelium from the basement membrane towards the tubular lumen, and at the same time for their attachment to Sertoli cells for support. This review will summarize the recent findings that focus on the role of hormones (FSH and testosterone) and cytokines (transforming growth factor-βs and tumor necrosis factor-α) on cell junction restructuring in the testis and the molecular mechanisms.

Wnt5a Regulates Junctional Function of Sertoli cells Through PCP-Mediated Effects on mTORC1 and mTORC2

Endocrinology ◽  
2021 ◽  
Author(s):  
Yan Fu ◽  
Yuexin Wei ◽  
Yu Zhou ◽  
Huan Wu ◽  
Yifan Hong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Wnt Signaling Pathway ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Cell Junction ◽  
Specific Expression

Abstract The blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli-germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells and then identified elongated spermatids that lost their polarity, and were embedded in the seminiferous epithelium. Moreover, phagosomes were found near the tubule lumen. These defects were due to BTB and apical ES disruption. We also verified that the expression level and/or location of BTB-associated proteins, actin-binding proteins (ABPs) and F-actin was changed after Wnt5a knockdown in vivo and in vitro. Additionally, we demonstrated that Wnt5a regulated actin dynamics through Ror2-mediated mTORC1 and mTORC2. This study clarified the molecular mechanism of Wnt5a in Sertoli cell junctions through the planar cell polarity (PCP) signaling pathway. Our findings could provide an experimental basis for the clinical diagnosis and treatment of male infertility caused by Sertoli cell junction impairment.

scholarly journals Sertoli–germ cell junctions in the testis: a review of recent data

2010 ◽  
Vol 365 (1546) ◽  
pp. 1593-1605 ◽  
Author(s):  
Ilona A. Kopera ◽  
Barbara Bilinska ◽  
C. Yan Cheng ◽  
Dolores D. Mruk
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Molecular Architecture ◽  
Future Studies ◽  
Junction Type ◽  
Stage Viii ◽  
Immunological Barrier

Spermatogenesis is a process that involves an array of cellular and biochemical events, collectively culminating in the formation of haploid spermatids from diploid precursor cells known as spermatogonia. As germ cells differentiate from spermatogonia into elongated spermatids, they also progressively migrate across the entire length of the seminiferous epithelium until they reach the luminal edge in anticipation of spermiation at late stage VIII of spermatogenesis. At the same time, these germ cells must maintain stable attachment with Sertoli cells via testis-unique intermediate filament- (i.e. desmosome-like junctions) and actin- (i.e. ectoplasmic specializations, ESs) based cell junctions to prevent sloughing of immature germ cells from the seminiferous epithelium, which may result in infertility. In essence, both desmosome-like junctions and basal ESs are known to coexist between Sertoli cells at the level of the blood–testis barrier where they cofunction with the well-studied tight junction in maintaining the immunological barrier. However, the type of anchoring device that is present between Sertoli and germ cells depends on the developmental stage of the germ cell, i.e. desmosome-like junctions are present between Sertoli and germ cells up to, but not including, step 8 spermatids after which this junction type is replaced by the apical ES. While little is known about the biology of the desmosome-like junction in the testis, we have a relatively good understanding of the molecular architecture and the regulation of the ES. Here, we discuss recent findings relating to these two junction types in the testis, highlighting prospective areas that should be investigated in future studies.

Freeze-etch observations on the tight junctions of sertoli cells grown in organ culture with FSH

1978 ◽  
Vol 36 (2) ◽  
pp. 340-341
Author(s):  
Rita Meyer ◽  
Zoltan Posalaky ◽  
Dennis Mcginley
Keyword(s):  
Organ Culture ◽  
Tight Junctions ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Barrier Function ◽  
Cell Junction ◽  
Intramembranous Particles ◽  
Junctional Complexes ◽  
Oriented Parallel

The Sertoli cell tight junctional complexes have been shown to be the most important structural counterpart of the physiological blood-testis barrier. In freeze etch replicas they consist of extensive rows of intramembranous particles which are not only oriented parallel to one another, but to the myoid layer as well. Thus the occluding complex has both an internal and an overall orientation. However, this overall orientation to the myoid layer does not seem to be necessary to its barrier function. The 20 day old rat has extensive parallel tight junctions which are not oriented with respect to the myoid layer, and yet they are inpenetrable by lanthanum. The mechanism(s) for the control of Sertoli cell junction development and orientation has not been established, although such factors as the presence or absence of germ cells, and/or hormones, especially FSH have been implicated.

scholarly journals Establishment and applications of male germ cell and Sertoli cell lines

Reproduction ◽  
2016 ◽  
Vol 152 (2) ◽  
pp. R31-R40 ◽  
Author(s):  
Hong Wang ◽  
Liping Wen ◽  
Qingqing Yuan ◽  
Min Sun ◽  
Minghui Niu ◽  
...  
Keyword(s):  
Cell Line ◽  
Sertoli Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Simian Virus 40 ◽  
T Antigen ◽  
Seminiferous Tubules ◽  
Male Germ Cells

Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and Sertoli cells can have significant applications in treating male infertility and other diseases. However, primary male germ cells are hard to proliferatein vitroand the number of spermatogonial stem cells is scarce. Therefore, methods that promote the expansion of these cell populations are essential for their use from the bench to the bed side. Notably, a number of cell lines for rodent spermatogonia, spermatocytes and Sertoli cells have been developed, and significantly we have successfully established a human spermatogonial stem cell line with an unlimited proliferation potential and no tumor formation. This newly developed cell line could provide an abundant source of cells for uncovering molecular mechanisms underlying human spermatogenesis and for their utilization in the field of reproductive and regenerative medicine. In this review, we discuss the methods for establishing spermatogonial, spermatocyte and Sertoli cell lines using various kinds of approaches, including spontaneity, transgenic animals with oncogenes, simian virus 40 (SV40) large T antigen, the gene coding for a temperature-sensitive mutant ofp53, telomerase reverse gene (Tert), and the specific promoter-based selection strategy. We further highlight the essential applications of these cell lines in basic research and translation medicine.

scholarly journals Androgen Promotes Differentiation of PLZF+ Spermatogonia pool via Indirect Regulatory Pattern

2018 ◽  
Author(s):  
Jingjing Wang ◽  
Jinmei Li ◽  
Yunzhao Gu ◽  
Qin Xia ◽  
Weixiang Song ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Culture System ◽  
Molecular Mechanisms ◽  
Wilms Tumor ◽  
Post Partum ◽  
Mice Model ◽  
Androgen Action ◽  
Wilms Tumor 1

AbstractAndrogen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it’s interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulated Plzf (the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.

Structure and Function of Sertoli Cells

1976 ◽  
Vol 34 ◽  
pp. 16-17
Author(s):  
M. Dym
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Structure And Function ◽  
Seminiferous Epithelium ◽  
Cell Type ◽  
Germ Cell Differentiation ◽  
Full Control ◽  
Tubule Lumen ◽  
Strategic Position ◽  
And Function

The Sertoli cells perform an impressive array of functions in the testis. It is possible that the full control of germ cell differentiation is mediated by this elaborate cell type (Fig. 1). On the basis of its shape and strategic position within the seminiferous epithelium the functions of (1) support and nutrition have been assigned. Fawcett and Phillips (J. Reprod. Fert. 6: 405, 1969) demonstrated that the Sertoli cells engineer the (2) release of late spermatids into the tubule lumen; other data suggest that they are instrumental in the migration of the germ cells from the basal lamina to the lumen. Tight junctions between adjacent Sertoli cells subdivide the seminiferous epithelium into two compartments, basal and adluminal. These junctions form the (3) morphological basis of the blood-testis barrier . The Sertoli cells are capable of (4) phagocytizing vast numbers of degenerating germ cells and sperm residual bodies.

scholarly journals A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 583-594 ◽  
Author(s):  
Takeshi Sato ◽  
Yoshiakira Kanai ◽  
Takashi Noma ◽  
Masami Kanai-Azuma ◽  
Shinichiro Taya ◽  
...  
Keyword(s):  
Germ Cells ◽  
Granulosa Cells ◽  
Sertoli Cells ◽  
Translational Regulation ◽  
Expression Patterns ◽  
Intracellular Localization ◽  
Close Correlation ◽  
Cell Junction ◽  
Supporting Cells ◽  
Junction Protein

Usp9x, an X-linked deubiquitylating enzyme, is stage dependently expressed in the supporting cells (i.e. Sertoli cells and granulosa cells) and germ cells during mouse gametogenesis. Af-6, a cell junction protein, has been identified as a substrate of Usp9x, suggesting a possible association between Usp9x and Af-6 in spermatogenesis and oogenesis. In this study, we examined the expression pattern of Af-6 and Usp9x and their intracellular localization in testes and ovaries of mice treated with or without pregnant mare serum gonadotropin (PMSG), an FSH-like hormone. In both testes and ovaries, Af-6 expression was predominantly observed in supporting cells, as well as in steroidogenic cells, but not in any germ cells. In Sertoli cells, Af-6 was continuously expressed throughout postnatal and adult stages, where both Af-6 and Usp9x were enriched at the sites of Sertoli–Sertoli and Sertoli–spermatid junctions especially at stages XI–VI. In the granulosa cells, Af-6, as well as Usp9x, was highly expressed in primordial and primary follicles, but its expression rapidly decreased after the late-secondary follicle stage. Interestingly, in PMSG-treated mice, the expression levels of Af-6 and Usp9x were synchronously enhanced, slightly in Sertoli cells and strongly in granulosa cells of the late-secondary and Graafian follicles. Such closely correlated expression patterns between Af-6 and Usp9x clearly suggest that Af-6 may be deubiquitylated by Usp9x in both Sertoli and granulosa cells. It further suggests that the post-translational regulation of Af-6 by Usp9x may be one potential pathway to control the cell adhesion dynamics in mammalian gametogenesis.

Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development

2002 ◽  
Vol 82 (4) ◽  
pp. 825-874 ◽  
Author(s):  
C. Yan Cheng ◽  
Dolores D. Mruk
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Biology ◽  
Cell Communication ◽  
Seminiferous Epithelium ◽  
Cell Junction ◽  
In Vivo Models ◽  
Blood Testis Barrier

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

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