Dysregulation of acrosome formation network by 8-oxoguanine (8-oxoG) in infertile sperm
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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 |
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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-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.
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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-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:43 biopsies were obtained from subfertile/infertile patients undergoing testicular sperm extraction (TESE) as part of their treatment. Labelled cDNAs were compared to a reference normal testis RNA (Ambion).
2007-03-15 | E-MEXP-1019 | biostudies-arrayexpress
Project description:Infertility is a widespread health problem, with rising incidence worldwide. Whether the infertility is caused by genetic or environmental factors, the reason for inability to reproduce can be the too low number of sperm or morphological or functional abnormality of the sperm. Therefore there can be a certain possibility that divergent causes would converge in common mechanisms impairing sperm functionality. A key step in the control of the cell phenotype is the regulation of gene expression. Therefore, the sperm transcriptome can reflect the impairment of proper regulatory networks acting during spermatogenesis and later, during sperm maturation. Also, it can be speculated that some sperm RNAs can influence the fitness of the early embryo, despite the small amount of sperm RNA. Although the changes in transcriptome are not always reflected by similar changes in the proteome, a relative ease of transcriptome interrogation makes it an excellent tool for hypothesis generation about infertility mechanisms and for a search for potential infertility biomarkers.
2021-11-03 | GSE160749 | GEO
Project description:Alterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility). We started the present project to with the goal to characterize the RNA expression in asthenozoospermic infertile patients as compared to normozoospermic fertile controls. We selected four normal fertile donors and four severe asthenozoospermic infertile patients. Equal amounts of RNA were extracted from the sperm samples, subjected to different quality controls and hybridized to the Affymetrix U133 Plus version 2 arrays.
2012-03-15 | E-GEOD-34514 | biostudies-arrayexpress
Project description:We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple. NGS RNA-seq of 72 sperm samples from male partner of couples undergoing fertility treatment
2015-07-09 | E-GEOD-65683 | biostudies-arrayexpress
Project description:We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple.
2015-07-09 | GSE65683 | GEO
Project description:Decreased piRNAs in infertile semen are related to downregulation of sperm MitoPLD expression
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