Effects of deletion of Arhgef15 gene in mouse sertoli cells on spermatogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA848795 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19638125_1.fastq.gz | Fastqsanger.gz | |||
| SRR19638125_2.fastq.gz | Fastqsanger.gz | |||
| SRR19638126_1.fastq.gz | Fastqsanger.gz | |||
| SRR19638126_2.fastq.gz | Fastqsanger.gz | |||
| SRR19638127_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Sertoli cells, which are the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functions of ARHGEF15 in Sertoli cells during spermatogenesis using Sertoli cell–specific Arhgef15 knockout mice. The results showed that Arhgef15 deficiency in Sertoli cells affected the localization of Sertoli cell nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/Amh-Cre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in Sertoli cells of Arhgef15flox/flox/Amh-Cre+ mice were related to immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in Sertoli cells leads to sperm abnormality, probably by disrupting the testicular immune homeostasis, in mice.
2022-06-16 | GSE206018 | GEO
Project description:Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
2022-02-15 | PXD028051 | Pride
Project description:Elevated palmitic acid, a most abundant saturated fatty acid, is a risk factor for obesity complications. Here, we report that palmitic acid impairs spermatogenesis by inducing abnormal palmitoylation in Sertoli cells. Firstly, we proposed a correlation between palmitic acid and spermatogenesis by reporting a significant elevation of serum palmitic acid levels in patients with dyszoospermia. In palmitic acid -treated mice, the blood-testis barrier was found to be disrupted, and decreased tight junction protein expression was observed in palmitic acid-treated Sertoli cells. Palmitic acid entered the endoplasmic reticulum and induced endoplasmic reticulum stress, resulting in damage to Sertoli cell barriers.
2022-08-12 | PXD028778 | Pride
Project description:The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. Germ cell loss was found in Wt1 knockout mice. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. We used Digital Gene Expression Tag Profiling to detail the global programme of gene expression after Wt1 deletion in sertoli cell and identified 710 gene expression level change more than 2 times. Digital Gene Expression Tag Profiling analysis were performed using mRNA from control and Wt1-deficient Primary Sertoli cells, every group primare sertoli cell were from more than 30 mice.
2014-05-06 | E-GEOD-46664 | biostudies-arrayexpress
Project description:The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. Germ cell loss was found in Wt1 knockout mice. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. We used Digital Gene Expression Tag Profiling to detail the global programme of gene expression after Wt1 deletion in sertoli cell and identified 710 gene expression level change more than 2 times.
2014-05-06 | GSE46664 | GEO
Project description:To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the ""strongly"" upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. This particular series represents all data from d 10. The additional expression data from the time course (d8-d20) is represented by series GSE2259 (Testicular gene expression in SCARKO mice during prepuberty). Keywords = SCARKO Keywords = testis Keywords = spermatogenesis Keywords = androgens Keywords = microarray Keywords = Pem Keywords = serine protease inhibitor
2007-09-25 | E-GEOD-2260 | biostudies-arrayexpress
Project description:<p>Sertoli cell-only syndrome is severe form of human male infertility in which most seminiferous tubules appear to lack all spermatogenic cells, including spermatogonial stem cells (SSCs). However, a few small tubule segments of some patients have active spermatogenesis and, thus, functional stem cell niches and SSCs. Normally SSCs replicate, migrate and refill adjacent empty niches, but this does not appear to occur in SCO syndrome. We hypothesized that this failure occurs because most niches are dysfunctional. As Sertoli cells are essential to formation of these niches, we used RNAseq to compare the transcriptomes of human testes with qualitatively normal (complete) spermatogenesis (n=4) with the transcriptomes of human testes with SCO syndrome (n=7). We then focused our analysis on the expression of transcripts that bioinformatic analyses identified as Sertoli cell signature transcripts. Results show that Sertoli cells in SCO testes express abnormally low levels of GDNF, FGF8 and BMP4, all of which are important regulators of mouse SSCs and/or progenitor spermatogonia. Sertoli cells in SCO testes express significantly reduced levels of transcripts for proteins that polarize the Sertoli cell plasma membrane and regulate the trafficking of cell adhesion and gap junction proteins in and out of that plasma membrane.</p>
| phs001777 | dbGaP
Project description:To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the "strongly" upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. This series represents the time course data from d 8, d 10, d 12, d 16 and d 20. The expression data from the additional SCARKO vs control comparison on d 10 is represented by series GSE2260 (Testicular gene expression in SCARKO mice at day 10). Keywords = SCARKO Keywords = testis Keywords = spermatogenesis Keywords = androgens Keywords = microarray Keywords = Pem Keywords = serine protease inhibitor
2007-09-25 | E-GEOD-2259 | biostudies-arrayexpress
Project description:To investigated the function of SRSF2 in Sertoli cells, we generated the specific deletion of Srsf2 in Sertoli cells.
2023-11-01 | GSE218969 | GEO
Project description:Sertoli cells are highly polarized testicular cells that provide a nurturing environment for germ cell development and maturation during spermatogenesis. The Class III PI3K, PIK3C3/VPS34 plays key roles in endosomal membrane traffic and macroautophagy in various cell types; however, its role in Sertoli cells remains unclear. Here, we generated a mouse line in which Pik3c3 was specifically deleted in Sertoli cells (cKO) and found that after one round of normal spermatogenesis, the cKO mice quickly became infertile and showed disruption of Sertoli cell polarity, loss of germ cells and impaired spermiogenesis. Subsequent proteomics and phosphoproteomics analyses enriched the F-actin cytoskeleton network involved in the disorganized Sertoli-cell structure in cKO testis, and showed significantly increased expression of the F-actin negative regulator SCIN and reduced phosphorylation of the α-tubulin deacetylase HDAC6. Our results further demonstrated that the accumulation of SCIN in cKO Sertoli cells caused the disassembly of the F-actin cytoskeleton, which was related to the failure of SCIN degradation through the autophagy-lysosome pathway. Additionally, we found that the phosphorylation of HDAC6 at site S59 by PIK3C3 was essential for its degradation through the ubiquitin-proteasome pathway. As a result, the HDAC6 that accumulated in cKO Sertoli cells deacetylated SCIN at site K189 and led to a disorganized F-actin cytoskeleton. Taken together, our findings elucidate the indispensable role of PIK3C3 in maintaining Sertoli cell polarity and reveal a new mechanism in which both its protein kinase activity and its regulation of autophagy are required for the stabilization of the actin cytoskeleton.
2024-08-09 | PXD036242 | Pride