scholarly journals PA1 Participates in the Maintenance of Blood-Testis Barrier Integrity via Cooperation with JUN in the Sertoli Cells of Mice.

2021 ◽  
Author(s):  
Bo Liu ◽  
Chao Liu ◽  
Binfang Ma ◽  
Ruidan Zhang ◽  
Zhiwei Zhao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Sertoli Cells ◽  
Normal Function ◽  
Male Reproduction ◽  
Biological Processes ◽  
Actin Organization ◽  
Cellular Junctions ◽  
Human And Mouse ◽  
Ectoplasmic Specialization ◽  
Blood Testis Barrier

Abstract BackgroundThe blood-testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown. ResultsHere, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1. ConclusionOverall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia.

scholarly journals Benzo(a)pyrene (B[a]P) and its adverse effects on male testis

2018 ◽  
Author(s):  
Wei Liu ◽  
Aihua Gu
Keyword(s):  
Body Weight ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Treated Group ◽  
Male Reproduction ◽  
Adverse Impact ◽  
Phase Cell ◽  
Seminiferous Tubules ◽  
Blood Testis Barrier

ABSTRACTIt has been proved that Benzo(a)pyrene (B[a]P) is mutagenic in somatic cells, whereas the adverse effect of BaP on male reproduction remains unclear. To investigate whether it can pass through the blood-testis barrier (BTB) and its potential reproductive toxicology and molecular mechanisms, mice were exposed to B[a]P (there are two doses, that is 13mg/kg body weight and 26 mg/kg body weight; three times per week) during 6 weeks and sacrificed 6 weeks after the final exposure to obtain B[a]P-exposed testis, blood and others. Electron microscopy analysis was performed to confirm whether the integrity of BTB and the ultra-structure changes in testes of B[a]P treated mice, which showed that the integrity of the BTB was disrupted, accompanied with the structure of sertoli cells seriously damaged, including the integrity of the nuclear membrane of the sertoli cells impaired and the basement membrane of the seminiferous tubules disrupted. X-ray imaging in vitro told us that BaP can overgo the BTB and gathered in the testis of mice. We found the significantly decreased expression of ZO-1, occludin, N-cadherin, vimentin and claudin-1 in the testes of B[a]P treated group by immunofluorescence detection. B[a]P induced BTB component protein decreased were also found in TM4 cells exposed to 5μmol/L B[a]P for 24h. We found a significantly decrease of testosterone level and a significantly increase of estrogen level in the serum of treated groups comparing with the control one by radioimmunoassay. TM4 cells, MLTC-1 cells and GC-2 cells was cultured with medium contains B[a]P. MTT Cell Proliferation and Cytotoxicity Assay, cell apoptosis analysis, FACScan analyzer, We observed apparent increase of TM4 and GC-2 cells apoptosis after expose to B[a]P for 24h. B[a]P induced TM4 cell, GC-2 cell and MLTC-1 cell G2/M phase cell arrest. In conclusion, these results suggested that BaP has an adverse impact on male reproduction, it can cross the blood-testis barrier and damage it, the component proteins of the BTB significantly decreased, it can also produce adverse impact on male germ cells.

scholarly journals rpS6 Regulates Blood-Testis Barrier Dynamics By Affecting F-Actin Organization and Protein Recruitment

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 5036-5048 ◽  
Author(s):  
Ka-Wai Mok ◽  
Dolores D. Mruk ◽  
Bruno Silvestrini ◽  
C. Yan Cheng
Keyword(s):  
Sertoli Cell ◽  
Actin Filament ◽  
Sertoli Cells ◽  
Plasma Membranes ◽  
Permeability Barrier ◽  
Actin Organization ◽  
Filament Bundles ◽  
Mtorc1 Pathway ◽  
Protein Recruitment ◽  
Blood Testis Barrier

Abstract During spermatogenesis, preleptotene spermatocytes residing near the basement membrane of the seminiferous tubule must traverse the blood-testis barrier (BTB) at stage VIII–IX of the epithelial cycle to continue their development in the adluminal compartment. Unlike other blood-tissue barriers (e.g. the blood-brain barrier) that are created by the endothelial tight junction (TJ) barrier of capillaries, the BTB is created by specialized junctions between Sertoli cells in which TJ coexists with basal ectoplasmic specialization (basal ES, a testis-specific adherens junction). The basal ES is typified by the presence of tightly packed actin filament bundles sandwiched between cisternae of endoplasmic reticulum and the apposing plasma membranes of Sertoli cells. These actin filament bundles also confer unusual adhesive strength to the BTB. Yet the mechanisms by which these filamentous actin (F-actin) networks are regulated from the bundled to the debundled state to facilitate the transit of spermatocytes remain elusive. Herein, we provide evidence that ribosomal protein S6 (rpS6), the downstream signaling molecule of the mammalian target of rapamycin complex 1 (mTORC1) pathway, is a major regulator of F-actin organization and adhesion protein recruitment at the BTB. rpS6 is restrictively and spatiotemporally activated at the BTB during the epithelial cycle. An activation of rpS6 led to a disruption of the Sertoli cell TJ barrier and BTB integrity. Its silencing in vitro or in vivo by using small interfering RNA duplexes or short hairpin RNA was found to promote the Sertoli cell TJ permeability barrier by the recruitment of adhesion proteins (e.g. claudin-11 and occludin) to the BTB. Thus, rpS6 in the mTORC1 pathway regulates BTB restructuring via its effects on the F-actin organization and protein recruitment at the BTB.

scholarly journals Perfluorooctanesulfonate (PFOS) Perturbs Male Rat Sertoli Cell Blood-Testis Barrier Function by Affecting F-Actin Organization via p-FAK-Tyr407: An in Vitro Study

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 249-262 ◽  
Author(s):  
Hin-Ting Wan ◽  
Dolores D. Mruk ◽  
Chris K. C. Wong ◽  
C. Yan Cheng
Keyword(s):  
Tight Junction ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Male Rat ◽  
Environmental Toxicants ◽  
Adhesion Proteins ◽  
Actin Organization ◽  
Blood Testis Barrier

Environmental toxicants such as perfluorooctanesulfonate (PFOS) have been implicated in male reproductive dysfunction, including reduced sperm count and semen quality, in humans. However, the underlying mechanism(s) remains unknown. Herein PFOS at 10–20 μM (∼5–10 μg/mL) was found to be more potent than bisphenol A (100 μM) in perturbing the blood-testis barrier (BTB) function by disrupting the Sertoli cell tight junction-permeability barrier without detectable cytotoxicity. We also delineated the underlying molecular mechanism by which PFOS perturbed Sertoli cell BTB function using an in vitro model that mimics the BTB in vivo. First, PFOS perturbed F-actin organization in Sertoli cells, causing truncation of actin filaments at the BTB. Thus, the actin-based cytoskeleton was no longer capable of supporting the distribution and/or localization of actin-regulatory and adhesion proteins at the cell-cell interface necessary to maintain BTB integrity. Second, PFOS was found to perturb inter-Sertoli cell gap junction (GJ) communication based on a dye-transfer assay by down-regulating the expression of connexin-43, a GJ integral membrane protein. Third, phosphorylated focal adhesion kinase (FAK)-Tyr407 was found to protect the BTB from the destructive effects of PFOS as shown in a study via an overexpression of an FAK Y407E phosphomimetic mutant. Also, transfection of Sertoli cells with an FAK-specific microRNA, miR-135b, to knock down the expression of phosphorylated FAK-Tyr407 was found to worsen PFOS-mediated Sertoli cell tight junction disruption. In summary, PFOS-induced BTB disruption is mediated by down-regulating phosphorylated FAK-Tyr407 and connexin-43, which in turn perturbed F-actin organization and GJ-based intercellular communication, leading to mislocalization of actin-regulatory and adhesion proteins at the BTB.

scholarly journals Lycium barbarum Polysaccharide Ameliorates Heat-Stress-Induced Impairment of Primary Sertoli Cells and the Blood-Testis Barrier in Rat via Androgen Receptor and Akt Phosphorylation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Suqin Hu ◽  
Dianlong Liu ◽  
Sijia Liu ◽  
Chunrui Li ◽  
Jian Guo
Keyword(s):  
Heat Stress ◽  
Androgen Receptor ◽  
Sertoli Cells ◽  
Structural Integrity ◽  
Inhibitory Effect ◽  
Male Reproduction ◽  
Lycium Barbarum ◽  
Akt Phosphorylation ◽  
Lycium Barbarum Polysaccharide ◽  
Blood Testis Barrier

Male infertility induced by heat stress has been attracting more and more attention. Heat stress not only causes apoptosis of spermatocytes but also has adverse effects on Sertoli cells, further damaging spermatogenesis. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum, which has a protective effect on male reproduction, but its mechanism is still unclear. In this study, our results proved that LBP blocked the inhibitory effect on the proliferation activity of Sertoli cells after heat stress, reversed the dedifferentiation of Sertoli cells induced by heat stress, and ameliorated the structural integrity of the blood-testis barrier. In addition, it increased the expression of the androgen receptor and activated Akt signaling pathway to resist heat-stress-induced injury of Sertoli cells.

scholarly journals Kindlin-2 in Sertoli cells is essential for testis development and male fertility in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaochun Chi ◽  
Weiwei Luo ◽  
Jiagui Song ◽  
Bing Li ◽  
Tiantian Su ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Barrier Structure ◽  
Male Mice ◽  
Sperm Development

AbstractKindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.

scholarly journals Transcription Factors as the “Blitzkrieg” of Plant Defense: A Pragmatic View of Nitric Oxide’s Role in Gene Regulation

2021 ◽  
Vol 22 (2) ◽  
pp. 522
Author(s):  
Noreen Falak ◽  
Qari Muhammad Imran ◽  
Adil Hussain ◽  
Byung-Wook Yun
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Plant Defense ◽  
Systemic Acquired Resistance ◽  
Defense Mechanism ◽  
Regulation Of Gene Expression ◽  
Acquired Resistance ◽  
Biological Processes ◽  
Genetic Components ◽  
Transcriptional Changes

Plants are in continuous conflict with the environmental constraints and their sessile nature demands a fine-tuned, well-designed defense mechanism that can cope with a multitude of biotic and abiotic assaults. Therefore, plants have developed innate immunity, R-gene-mediated resistance, and systemic acquired resistance to ensure their survival. Transcription factors (TFs) are among the most important genetic components for the regulation of gene expression and several other biological processes. They bind to specific sequences in the DNA called transcription factor binding sites (TFBSs) that are present in the regulatory regions of genes. Depending on the environmental conditions, TFs can either enhance or suppress transcriptional processes. In the last couple of decades, nitric oxide (NO) emerged as a crucial molecule for signaling and regulating biological processes. Here, we have overviewed the plant defense system, the role of TFs in mediating the defense response, and that how NO can manipulate transcriptional changes including direct post-translational modifications of TFs. We also propose that NO might regulate gene expression by regulating the recruitment of RNA polymerase during transcription.

scholarly journals Comprehensive network modeling from single cell RNA sequencing of human and mouse reveals well conserved transcription regulation of hematopoiesis

BMC Genomics ◽  
2020 ◽  
Vol 21 (S11) ◽  
Author(s):  
Shouguo Gao ◽  
Zhijie Wu ◽  
Xingmin Feng ◽  
Sachiko Kajigaya ◽  
Xujing Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factors ◽  
Single Cell ◽  
Rna Sequencing ◽  
Transcription Regulation ◽  
Regulatory Networks ◽  
Stem Cell Differentiation ◽  
Hematopoietic Stem ◽  
Single Cell Rna Sequencing ◽  
Human And Mouse

Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs involved in flag leaf senescence of rice

2021 ◽  
Author(s):  
Xiaoping Huang ◽  
Hongyu Zhang ◽  
Qiang Wang ◽  
Rong Guo ◽  
Lingxia Wei ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Leaf Senescence ◽  
Flag Leaf ◽  
Reduction Process ◽  
Sequencing Analysis ◽  
Biological Processes ◽  
Genome Wide ◽  
A Genome ◽  
Non Coding Rnas ◽  
Systematic Identification

Abstract Key message This study showed the systematic identification of long non-coding RNAs (lncRNAs) involving in flag leaf senescence of rice, providing the possible lncRNA-mRNA regulatory relationships and lncRNA-miRNA-mRNA ceRNA networks during leaf senescence. Abstract LncRNAs have been reported to play crucial roles in diverse biological processes. However, no systematic identification of lncRNAs associated with leaf senescence in plants has been studied. In this study, a genome-wide high throughput sequencing analysis was performed using rice flag leaves developing from normal to senescence. A total of 3953 lncRNAs and 38757 mRNAs were identified, of which 343 lncRNAs and 9412 mRNAs were differentially expressed. Through weighted gene co-expression network analysis (WGCNA), 22 continuously down-expressed lncRNAs targeting 812 co-expressed mRNAs and 48 continuously up-expressed lncRNAs targeting 1209 co-expressed mRNAs were considered to be significantly associated with flag leaf senescence. Gene Ontology results suggested that the senescence-associated lncRNAs targeted mRNAs involving in many biological processes, including transcription, hormone response, oxidation–reduction process and substance metabolism. Additionally, 43 senescence-associated lncRNAs were predicted to target 111 co-expressed transcription factors. Interestingly, 8 down-expressed lncRNAs and 29 up-expressed lncRNAs were found to separately target 12 and 20 well-studied senescence-associated genes (SAGs). Furthermore, analysis on the competing endogenous RNA (CeRNA) network revealed that 6 down-expressed lncRNAs possibly regulated 51 co-expressed mRNAs through 15 miRNAs, and 14 up-expressed lncRNAs possibly regulated 117 co-expressed mRNAs through 21 miRNAs. Importantly, by expression validation, a conserved miR164-NAC regulatory pathway was found to be possibly involved in leaf senescence, where lncRNA MSTRG.62092.1 may serve as a ceRNA binding with miR164a and miR164e to regulate three transcription factors. And two key lncRNAs MSTRG.31014.21 and MSTRG.31014.36 also could regulate the abscisic-acid biosynthetic gene BGIOSGA025169 (OsNCED4) and BGIOSGA016313 (NAC family) through osa-miR5809. The possible regulation networks of lncRNAs involving in leaf senescence were discussed, and several candidate lncRNAs were recommended for prior transgenic analysis. These findings will extend the understanding on the regulatory roles of lncRNAs in leaf senescence, and lay a foundation for functional research on candidate lncRNAs.

Nucleoside Transport at the Blood-Testis Barrier Studied with Primary-Cultured Sertoli Cells

2004 ◽  
Vol 312 (2) ◽  
pp. 601-608 ◽  
Author(s):  
Ryo Kato ◽  
Tomoji Maeda ◽  
Toshihiro Akaike ◽  
Ikumi Tamai
Keyword(s):  
Sertoli Cells ◽  
Nucleoside Transport ◽  
Blood Testis Barrier
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