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 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 UXT in Sertoli cells is required for blood–testis barrier integrity†

2020 ◽  
Vol 103 (4) ◽  
pp. 880-891
Author(s):  
Phillip A Thomas ◽  
Eric D Schafler ◽  
Sophie E Ruff ◽  
Maud Voisin ◽  
Susan Ha ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Structural Integrity ◽  
Cell Function ◽  
Somatic Tissue ◽  
Seminiferous Tubules ◽  
Testis Size ◽  
Conditional Deletion ◽  
Blood Testis Barrier

Abstract Spermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell’s ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood–testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT’s role in Sertoli cells and its contribution to the structural integrity of the BTB.

scholarly journals Musashi-1 maintains blood–testis barrier structure during spermatogenesis and regulates stress granule formation upon heat stress

2015 ◽  
Vol 26 (10) ◽  
pp. 1947-1956 ◽  
Author(s):  
Sun ErLin ◽  
Wei WenJie ◽  
Wang LiNing ◽  
Lu BingXin ◽  
Lei MingDe ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cell Fate ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Associated Proteins ◽  
Blood Testis Barrier

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood–testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1–knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling.

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.

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules

2020 ◽  
Vol 17 (5) ◽  
pp. 438-446 ◽  
Author(s):  
Yuanyuan Li ◽  
Mohammad Ishraq Zafar ◽  
Xiaotong Wang ◽  
Xiaofang Ding ◽  
Honggang Li
Keyword(s):  
Drug Delivery ◽  
Heat Stress ◽  
Targeted Drug Delivery ◽  
Therapeutic Agents ◽  
Seminiferous Tubules ◽  
Adult Mice ◽  
Targeted Drug ◽  
To Receive ◽  
Unfocused Ultrasound ◽  
Blood Testis Barrier

Aim: To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. Background: The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. Objectives: To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. Material & Methods: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. Results: As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. Conclusion: The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.

scholarly journals CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

2019 ◽  
Vol 12 (2) ◽  
pp. 89
Author(s):  
Janeen H. Trembley ◽  
Betsy T. Kren ◽  
Md. J. Abedin ◽  
Daniel P. Shaughnessy ◽  
Yingming Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Inhibitory Effect ◽  
Strongly Correlated ◽  
Protein Levels ◽  
Small Molecule Inhibition ◽  
Prostate Cells ◽  
Cell Death Response ◽  
Stress Signals ◽  
Castrate Resistant

The prosurvival protein kinase CK2, androgen receptor (AR), and nuclear factor kappa B (NFκB) interact in the function of prostate cells, and there is evidence of crosstalk between these signals in the pathobiology of prostate cancer (PCa). As CK2 is elevated in PCa, and AR and NFκB are involved in the development and progression of prostate cancer, we investigated their interaction in benign and malignant prostate cells in the presence of altered CK2 expression. Our results show that elevation of CK2 levels caused increased levels of AR and NFκB p65 in prostate cells of different phenotypes. Analysis of TCGA PCa data indicated that AR and CK2α RNA expression are strongly correlated. Small molecule inhibition or molecular down-regulation of CK2 caused reduction in AR mRNA expression and protein levels in PCa cells and in orthotopic xenograft tumors by various pathways. Among these, regulation of AR protein stability plays a unifying role in CK2 maintenance of AR protein levels. Our results show induction of various endoplasmic reticulum stress signals after CK2 inhibition, which may play a role in the PCa cell death response. Of note, CK2 inhibition caused loss of cell viability in both parental and enzalutamide-resistant castrate-resistant PCa cells. The present work elucidates the specific link of CK2 to the pathogenesis of PCa in association with AR and NFκB expression; further, the observation that inhibition of CK2 can exert a growth inhibitory effect on therapy-resistant PCa cells emphasizes the potential utility of CK2 inhibition in patients who are on enzalutamide treatment for advanced cancer.

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