scholarly journals Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: An in vivo study using an androgen suppression model

2005 ◽  
Vol 205 (1) ◽  
pp. 141-157 ◽  
Author(s):  
Weiliang Xia ◽  
Ching Hang Wong ◽  
Nikki P.Y. Lee ◽  
Will M. Lee ◽  
C. Yan Cheng
Keyword(s):  
Cell Adhesion ◽  
Germ Cell ◽  
Adherens Junctions ◽  
Seminiferous Epithelium ◽  
In Vivo Study ◽  
Barrier Integrity ◽  
Rat Testis ◽  
Androgen Suppression ◽  
Blood Testis Barrier

scholarly journals An in Vivo Study on Adjudin and Blood-Testis Barrier Dynamics

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4724-4733 ◽  
Author(s):  
Ilona A. Kopera ◽  
Linlin Su ◽  
Barbara Bilińska ◽  
C. Yan Cheng ◽  
Dolores D. Mruk
Keyword(s):  
Cell Adhesion ◽  
Tight Junction ◽  
Germ Cell ◽  
Cell Loss ◽  
Seminiferous Epithelium ◽  
Rat Pups ◽  
Old Rats ◽  
Ectoplasmic Specialization ◽  
Blood Testis Barrier

Abstract Adjudin is known to specifically affect Sertoli-germ cell adhesion, resulting in germ cell loss from the seminiferous epithelium and transient infertility. The apical ectoplasmic specialization (ES) was shown to be the primary target of adjudin because adhesion was unaffected in organs that lack this structure. Herein we expand previous findings by treating rat pups with adjudin, and we aimed to address two questions. First, can adjudin perturb germ cell adhesion in the seminiferous epithelium of testes in which the apical ES is not yet present? Second, can adjudin affect assembly of the blood-testis barrier (BTB) at 15–18 d of age? Interesting changes were noted when aged-matched testes from control and adjudin-treated rats were examined, including a delay in the appearance of developing germ cells as well as a delay in the formation of the tubule lumen. Immunoblotting using antibodies against BTB-constituent proteins indicated that formation of the BTB was affected in rat pups gavaged with adjudin. These results were corroborated by immunofluorescence microscopy, which showed profound changes in the cellular distribution of tight junction and basal ES proteins. Moreover, the BTB was shown to be compromised in 30-d-old rats when its integrity was assessed by a functional in vivo assay. By 45 d of age, however, the seminiferous epithelium of treated rats was indistinguishable from that of control rats. Collectively these results demonstrate that adjudin targets the apical ES as well as the basal ES and tight junction, which in turn delays assembly of the BTB.

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.

An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity

10.3791/58512 ◽  
2018 ◽  
Author(s):  
Mengrou Liu ◽  
Chunsen Zhu ◽  
Shun Bai ◽  
Xin Li ◽  
Kaiqiang Fu ◽  
...  
Keyword(s):  
Mouse Blood ◽  
Barrier Integrity ◽  
Em Method ◽  
Blood Testis Barrier

scholarly journals Dynein 1 supports spermatid transport and spermiation during spermatogenesis in the rat testis

2018 ◽  
Vol 315 (5) ◽  
pp. E924-E948 ◽  
Author(s):  
Qing Wen ◽  
Elizabeth I. Tang ◽  
Wing-yee Lui ◽  
Will M. Lee ◽  
Chris K. C. Wong ◽  
...  
Keyword(s):  
Germ Cell ◽  
Heavy Chain ◽  
Sertoli Cells ◽  
Cytoplasmic Dynein ◽  
Seminiferous Epithelium ◽  
Organelle Transport ◽  
Cellular Events

In the mammalian testis, spermatogenesis is dependent on the microtubule (MT)-specific motor proteins, such as dynein 1, that serve as the engine to support germ cell and organelle transport across the seminiferous epithelium at different stages of the epithelial cycle. Yet the underlying molecular mechanism(s) that support this series of cellular events remain unknown. Herein, we used RNAi to knockdown cytoplasmic dynein 1 heavy chain (Dync1h1) and an inhibitor ciliobrevin D to inactivate dynein in Sertoli cells in vitro and the testis in vivo, thereby probing the role of dynein 1 in spermatogenesis. Both treatments were shown to extensively induce disruption of MT organization across Sertoli cells in vitro and the testis in vivo. These changes also perturbed the transport of spermatids and other organelles (such as phagosomes) across the epithelium. These changes thus led to disruption of spermatogenesis. Interestingly, the knockdown of dynein 1 or its inactivation by ciliobrevin D also perturbed gross disruption of F-actin across the Sertoli cells in vitro and the seminiferous epithelium in vivo, illustrating there are cross talks between the two cytoskeletons in the testis. In summary, these findings confirm the role of cytoplasmic dynein 1 to support the transport of spermatids and organelles across the seminiferous epithelium during the epithelial cycle of spermatogenesis.

scholarly journals c-Yes regulates cell adhesion at the apical ectoplasmic specialization-blood-testis barrier axis via its effects on protein recruitment and distribution

2013 ◽  
Vol 304 (2) ◽  
pp. E145-E159 ◽  
Author(s):  
Xiang Xiao ◽  
Dolores D. Mruk ◽  
C. Yan Cheng
Keyword(s):  
Cell Adhesion ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Early Stage ◽  
Seminiferous Epithelium ◽  
Permeability Barrier ◽  
Cell Interface ◽  
Ectoplasmic Specialization ◽  
Cell Cell ◽  
Blood Testis Barrier

During spermatogenesis, extensive restructuring takes place at the cell-cell interface since developing germ cells migrate progressively from the basal to the adluminal compartment of the seminiferous epithelium. Since germ cells per se are not motile cells, their movement relies almost exclusively on the Sertoli cell. Nonetheless, extensive exchanges in signaling take place between these cells in the seminiferous epithelium. c-Yes, a nonreceptor protein tyrosine kinase belonging to the Src family kinases (SFKs) and a crucial signaling protein, was recently shown to be upregulated at the Sertoli cell-cell interface at the blood-testis barrier (BTB) at stages VIII–IX of the seminiferous epithelial cycle of spermatogenesis. It was also highly expressed at the Sertoli cell-spermatid interface known as apical ectoplasmic specialization (apical ES) at stage V to early stage VIII of the epithelial cycle during spermiogenesis. Herein, it was shown that the knockdown of c-Yes by RNAi in vitro and in vivo affected both Sertoli cell adhesion at the BTB and spermatid adhesion at the apical ES, causing a disruption of the Sertoli cell tight junction-permeability barrier function, germ cell loss from the seminiferous epithelium, and also a loss of spermatid polarity. These effects were shown to be mediated by changes in distribution and/or localization of adhesion proteins at the BTB (e.g., occludin, N-cadherin) and at the apical ES (e.g., nectin-3) and possibly the result of changes in the underlying actin filaments at the BTB and the apical ES. These findings implicate that c-Yes is a likely target of male contraceptive research.

scholarly journals Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation

2020 ◽  
Vol 295 (22) ◽  
pp. 7669-7685 ◽  
Author(s):  
Panfeng Fu ◽  
Ramaswamy Ramchandran ◽  
Mark Shaaya ◽  
Longshuang Huang ◽  
David L. Ebenezer ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protein Tyrosine Phosphatase ◽  
Barrier Function ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Protein Tyrosine ◽  
Adhesion Junctions

Increased permeability of vascular lung tissues is a hallmark of acute lung injury and is often caused by edemagenic insults resulting in inflammation. Vascular endothelial (VE)-cadherin undergoes internalization in response to inflammatory stimuli and is recycled at cell adhesion junctions during endothelial barrier re-establishment. Here, we hypothesized that phospholipase D (PLD)-generated phosphatidic acid (PA) signaling regulates VE-cadherin recycling and promotes endothelial barrier recovery by dephosphorylating VE-cadherin. Genetic deletion of PLD2 impaired recovery from protease-activated receptor-1–activating peptide (PAR-1–AP)-induced lung vascular permeability and potentiated inflammation in vivo. In human lung microvascular endothelial cells (HLMVECs), inhibition or deletion of PLD2, but not of PLD1, delayed endothelial barrier recovery after thrombin stimulation. Thrombin stimulation of HLMVECs increased co-localization of PLD2-generated PA and VE-cadherin at cell-cell adhesion junctions. Inhibition of PLD2 activity resulted in prolonged phosphorylation of Tyr-658 in VE-cadherin during the recovery phase 3 h post-thrombin challenge. Immunoprecipitation experiments revealed that after HLMVECs are thrombin stimulated, PLD2, VE-cadherin, and protein-tyrosine phosphatase nonreceptor type 14 (PTPN14), a PLD2-dependent protein-tyrosine phosphatase, strongly associate with each other. PTPN14 depletion delayed VE-cadherin dephosphorylation, reannealing of adherens junctions, and barrier function recovery. PLD2 inhibition attenuated PTPN14 activity and reversed PTPN14-dependent VE-cadherin dephosphorylation after thrombin stimulation. Our findings indicate that PLD2 promotes PTPN14-mediated dephosphorylation of VE-cadherin and that redistribution of VE-cadherin at adherens junctions is essential for recovery of endothelial barrier function after an edemagenic insult.

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