Dysregulation of acrosome formation network by 8-oxoguanine (8-oxoG) in infertile sperm
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA694920 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13531052_1.fastq.gz | Fastqsanger.gz | |||
| SRR13531052_2.fastq.gz | Fastqsanger.gz | |||
| SRR13531053_1.fastq.gz | Fastqsanger.gz | |||
| SRR13531053_2.fastq.gz | Fastqsanger.gz | |||
| SRR13531054_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Various environmental factors contribute to dysregulated spermatogenic gene network, abnormal spermatogenesis, and eventually impaired sperm fertility. 8-hydroxyguanine (8-oxoG) is the most common and well-studied oxidative DNA lesion of the four DNA bases and unrepaired 8-oxoG modifications are associated with DNA fragmentation in sperms. However, the molecular effects of 8-oxoG generated in sperm DNA by oxidative stress on spermatogenesis are not entirely understood. Here, we identified one infertile Korean native striped cattle at 6-year old (C14) due to asthenozoospermia and teratozoospermia. We compared global concentration of 8-oxoG by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), the genomic distribution of 8-oxoG by next-generation sequencing (OG-seq), and expression of sperm proteins by 2-dimensional electrophoresis followed by mass spectrometry (2D/MS) in sperms of C14 with those of normal counterpart (C13). We found that averaged levels of 8-oxoG in C13 and C14 sperms were 0.027% and 0.044% of total dG and 8-oxoG was significantly greater in infertile sperm DNA (p = 0.0028). More than 81% of the 8-oxoG loci were distributed around the transcription start site (TSS) and 8-oxoG harboring 165 genes, including phospholipases, were annotated exclusively into infertile sperm DNA. Gene set enrichment analysis (GSEA) and the protein-protein interaction networking revealed that the Golgi apparatus was significantly enriched with the 8-oxoG genes of infertile sperm (q = 2.20E-07). Proteomic analysis verified that acrosome-related proteins including Acrosin-binding protein (ACRBP) and Sperm equatorial segment protein 1 (SPESP1) were 1.6-fold and 2.6-fold down-regulated in infertile sperm, respectively. These results suggest that 8-oxoG formation during spermatogenesis would dysregulate the acrosome-related gene network, causing structural and functional defects of sperm, leading to infertility.
2021-06-30 | GSE165538 | GEO
Project description:8-oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species. Here we show the genome-wide distribution of 8-oxoG by coupling immunoprecipitation by antibodies specific for the DNA fragments containing 8-oxoG with microarray that covers rat genome. Genome-wide mapping of 8-oxoG in rat kidney reveals that 8-oxoG preferentially located at gene deserts and depleted in genic regions. We did not observe the difference in 8-oxoG level between highly- and lowly-expressed groups of genes, may be because of the low level of 8-oxoG in genic regions in general comparing to gene deserts. Rather, the distribution of 8-oxoG highly correlates with the distribution of lamina associated domains (LADs), suggesting that the spatial location of the genomic regions in the nucleus is the major determinant for the susceptibility to oxidative modifications. One possible explanation for the enrichment of 8-oxoG in LADs is that the nuclear periphery is more susceptible to the oxidative damage coming from outside the nucleus. Another explanation is that LADs take rather compact conformation, which might prevent the recruitment of the repairing complex to the modified bases. Normal condition. Biological replicate 2
2014-01-13 | E-GEOD-54007 | biostudies-arrayexpress
Project description:8-Hydroxyguanine (8-oxoG) is the most common oxidative DNA lesion and unrepaired 8-oxoG is associated with DNA fragmentation in sperm. However, the molecular effects of 8-oxoG on spermatogenesis are not entirely understood. Here, we identified one infertile bull (C14) due to asthenoteratozoospermia. We compared the global concentration of 8-oxoG by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), the genomic distribution of 8-oxoG by next-generation sequencing (OG-seq), and the expression of sperm proteins by 2-dimensional polyacrylamide gel electrophoresis followed by peptide mass fingerprinting (2D-PAGE/PMF) in the sperm of C14 with those of a fertile bull (C13). We found that the average levels of 8-oxoG in C13 and C14 sperm were 0.027% and 0.044% of the total dG and it was significantly greater in infertile sperm DNA (p = 0.0028). Over 81% of the 8-oxoG loci were distributed around the transcription start site (TSS) and 165 genes harboring 8-oxoG were exclusive to infertile sperm. Functional enrichment and network analysis revealed that the Golgi apparatus was significantly enriched with the products from 8-oxoG genes of infertile sperm (q = 2.2 × 10-7). Proteomic analysis verified that acrosome-related proteins, including acrosin-binding protein (ACRBP), were downregulated in infertile sperm. These preliminary results suggest that 8-oxoG formation during spermatogenesis dysregulated the acrosome-related gene network, causing structural and functional defects of sperm and leading to infertility.
| S-EPMC8199233 | biostudies-literature
Project description:8-oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species. Here we show the genome-wide distribution of 8-oxoG by coupling immunoprecipitation by antibodies specific for the DNA fragments containing 8-oxoG with microarray that covers rat genome. Genome-wide mapping of 8-oxoG in rat kidney reveals that 8-oxoG preferentially located at gene deserts and depleted in genic regions. We did not observe the difference in 8-oxoG level between highly- and lowly-expressed groups of genes, may be because of the low level of 8-oxoG in genic regions in general comparing to gene deserts. Rather, the distribution of 8-oxoG highly correlates with the distribution of lamina associated domains (LADs), suggesting that the spatial location of the genomic regions in the nucleus is the major determinant for the susceptibility to oxidative modifications. One possible explanation for the enrichment of 8-oxoG in LADs is that the nuclear periphery is more susceptible to the oxidative damage coming from outside the nucleus. Another explanation is that LADs take rather compact conformation, which might prevent the recruitment of the repairing complex to the modified bases.
2014-01-13 | GSE54007 | GEO
Project description:Currently, the molecular mechanisms for the cause of male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with the fertile controls. By systematically screening piRNA profiles in sperms of fertile controls and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of infertile patients, which may provide pathophysiological clues about the development of infertility.
2021-07-06 | GSE172486 | GEO
Project description:8-oxoguanine is excised from DNA by 8-oxoguanine DNA glycosylase-1 during DNA base excision repair. We used microarrays to gain insight into the potential biological function of the excised, free 8-oxoguanine base. MRC5, human diploid fibroblasts were exposed to 8-oxoguanine and changes in gene expression compared to mock control were analyzed 6 hours after exposure. MRC5, human diploid fibroblasts were exposed to 8-oxoguanine and changes in gene expression compared to mock control were analyzed 12 hours after exposure.
2011-01-27 | E-GEOD-26813 | biostudies-arrayexpress
Project description:Purpose: The aim of this study is to test whether global gene expression induced by multiple challenges with OGG1-BER product 8-oxoG in mouse airways is linked to airway remodeling. Methods: RNAs extracted from individual mouse lungs (experimental group: n=5) were pooled and a total 1 ?g RNA was used for Next-Generation Sequencing (NGS) analyses on an Illumina HiSeq 1000 sequencing system. Sequence analyses were performed in duplicate. First- and second-strand synthesis, adapter ligation and amplification of the library were performed using the Illumina TruSeq Sample Preparation Kit as recommended by the manufacturer (Illumina). Library quailty was evaluated by using an Agilent DNA-1000 chip on an Agilent 2100 Bioanalyzer. Library DNA templates were quantitated by qPCR using known reference standards. Cluster formation of the library of DNA templates was performed using the TruSeq PE Cluster Kit v3 (Illumina) and the Illumina cBot workstation. Paired-end, 50-base sequencing was performed with a TruSeq SBS kit v3 (Illumina) on the Illumina HiSeq 1000 by protocols defined by the manufacturer. Base call conversion to sequence reads was performed using CASAVA-1.8.2. Sequence data were analyzed with the Bowtie2, Tophat2 and GFOLD programs. Processed data are presented as reads per kilobase transcript per million (RPKM), normalized to the experimental control (RNA from saline challenged lungs) and reported as fold change (test/control). Results: We mapped an average of 31.41 million sequence reads per sample and identified 23,337 transcripts in total RNA extracted from lungs of Balb/cJ mice as described in Methods. Approximately 14% of the transcripts showed differential expression between the saline-challenged control and 8-oxoguanine-challeged mouse lungs, with a fold change ?3.0. We validated the expression changes of 18 selected EMT-related genes of interest for our studies by qRT-PCR. Hierarchical clustering followed by Protein ANalysis THrough Evolutionary Relationships database (PANTHER) analysis of differentially expressed genes was done using GENE-E online software from Broad Institute (http://www.broadinstitute.org/cancer/software/GENE-E/). Results from PANTHER analysis of upregulated transcripts (fold change ?3.0) showed overrepresentation of various biological functions (GO terms) including developmental process (GO:0032502, P=4.58E-33), system development (GO:0048731, P=9.16E-33), cellular process (GO:0009987, P= 5.52E-31), cell adhesion (GO:0007155, P= 8.63E-28) among others. Pathway analysis (PANTHER) indicated that the most overrepresented pathways were: cadherin signaling (P00012, P=6.62E-07), wnt signaling (P00057, P= 5.81E-06), integrin signaling (P00034, P= 1.09E-05) among others. In addition to gene expression analysis, we confirmed airway remodeling by histological examination (Hematoxylin and Eosin, Masson's trichrome staining) of lung sections at seven days from the last challenge (day 11). Conclusions: This is the first study showing a link between gene expression at whole-transcriptome level induced by chronic OGG1-BER (mimicked by multiple challenges with 8-oxoG) and airway remodeling, supported by histological structural changes in lungs. Balb/cJ mice (5 per group) were intranasally challenged with 8-oxoguanine (1 µM, 60 µl) for three times at days 0, 2 and 4. Control group mice were intranasally challenged with saline (60 µl). At 30, 60 and 120 min after the third challenge (day 4), mice were sacrificed and lungs were processed for RNA extraction. RNAs from individual mice within the same group were pooled and subjected to deep-sequencing analysis in duplicate using NSG on an Illumina HiSeq 1000 sequencing system. After alignment and processing, the resulting RPKM from treatment groups (8-oxoG-challenged) were normalized to control group (saline-challenged).
2015-07-03 | E-GEOD-65031 | biostudies-arrayexpress
Project description:8-oxoguanine is excised from DNA by 8-oxoguanine DNA glycosylase-1 during DNA base excision repair. We used microarrays to gain insight into the potential biological function of the excised, free 8-oxoguanine base.
2011-01-27 | GSE26813 | GEO
Project description:8-oxo-7,8-dihydroguanine (8-oxoG) is a common RNA oxidation that has been implicated in carcinogenesis, neurodegeneration, and aging. Some? Many? RNA-binding proteins have shown binding preference for 8-oxoG modified RNA; such binding? can protect cells from oxidative stress. To date, the presence of specific 8-oxoG-recognizing proteins is only known in model organisms, but, how these proteins cooperate is still unclear. Here, we use RNA affinity chromatography and mass spectrometry to search for proteins that specifically bind 8-oxoG-modified RNA in Deinococcus radiodurans, an extremophilic bacterium with extraordinary resistance to oxidative stresses. We identified four proteins that selectively bind to oxidized RNA: polynucleotide phosphorylase (DR_2063/PNPase), ATP-dependent DEAD-box RNA helicase (DR_0335/RhlB), ribosomal protein S1 (DR_1983/RpsA), and transcriptional termination factor (DR_1338/Rho). The knockout of PNPase and RhlB in D. radiodurans caused increased sensitivity to hydrogen peroxide and a significant accumulation of 8-oxoG modified RNA. Importantly, PNPase directly interacts with RhlB in D. radiodurans; however, no additional phenotypic effect was observed for the double deletion of pnp and rhlB compared to the individual single deletions. Overall, our findings suggest a role of the PNPase-RhlB complex in targeting 8-oxoG-modified RNAs for rapid degradation and thereby constitutes an important component of D. radiodurans resistance to oxidative stress.
2022-07-10 | PXD028861 | Pride
Project description:We report the application of ChIP-Sequencing for profiling genome-wide distribution of 8-oxoguanine DNA glycosylase (OGG1) which is a DNA base excision repair protein, after TNF exposure of cells. By obtaining an average of over 18 million of total reads per sample and over 19.5 million of unique reads per sample from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HEK293 cells. We performed gene ontology and functional pathway analysis of genes associate with peaks, and identify regions of the genomes (e.g. promoter, introns, etc) where the peaks tend to occur. The results show that OGG1 is primarily associated with promoter regions in vicinity of transcription factor binding sites 5' of transcription start sites (TSS). This pattern of distribution occurs in spite of genome-wide oxidative modifications of guanine (primarily 8-oxoG). OGG1 increased highly significant (1e-09 to 1e-517) enrichment of 57 transcription factor binding sites including those for Sox(2, 3, 6, 10), RUNX, RUNX(1, 2), HOX(C, D), STAT(1, 3, 6), IRF(1 to 4), NF-κB. In controls, the DNA was chromatin immunoprecipitated using antibody to NF-κB/RelA. These and other data derived from further analysis, suggest that OGG1 modulates binding of transcription factors and gene expression.
2018-07-15 | GSE75562 | GEO