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Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2

ABSTRACT: Array-based DNA methylation profiling in peripheral blood leukocytes of 30 infertile men with impaired spermatogenesis as compared to 10 fertile men using the Illumina Infinium HumanMethylation 450k Bead Chip reveald 471 CpG sites (287 genes) to be differentially methylated between both groups. These CpG loci were significantly enriched for the gene ontology functions MHC class II receptor activity and piRNA binding. The latter was associated with two methylation-sensitive SNPs in the genes PIWIL1 and PIWIL2, respectivly, which showed significant allele distribution skewing in the infertile cohort. 445/471 differentially methylated CpGs were associated with SNPs, but 26 (15 genes) were not genomically templated and included the ENO1, MTA2, BRSK2 and LBX2 genes previously associated with fertility and spermatogenesis. The study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation to be associated with disturbed spermatogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE51245 | GEO | 2014/02/16

SECONDARY ACCESSION(S): PRJNA221869

REPOSITORIES: GEO

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Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2

Project description:Array-based DNA methylation profiling in peripheral blood leukocytes of 30 infertile men with impaired spermatogenesis as compared to 10 fertile men using the Illumina Infinium HumanMethylation 450k Bead Chip reveald 471 CpG sites (287 genes) to be differentially methylated between both groups. These CpG loci were significantly enriched for the gene ontology functions MHC class II receptor activity and piRNA binding. The latter was associated with two methylation-sensitive SNPs in the genes PIWIL1 and PIWIL2, respectivly, which showed significant allele distribution skewing in the infertile cohort. 445/471 differentially methylated CpGs were associated with SNPs, but 26 (15 genes) were not genomically templated and included the ENO1, MTA2, BRSK2 and LBX2 genes previously associated with fertility and spermatogenesis. The study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation to be associated with disturbed spermatogenesis. Bisulfite converted DNA of peripheral blood leukocytes from 30 infertile men and 10 fertile men as controls were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.

2014-02-16 | E-GEOD-51245 | biostudies-arrayexpress

Comparison of human epididymal gene expression in the caput epididymides of infertile and fertile patients

2007-10-05 | GSE9194 | GEO

Transcription profiling of of human epididymal gene expression in the caput epididymides of infertile and fertile patients

Project description:Caput epididymides biopsies from 4 patients suffering from non-obstructive azoospermia and from 4 patients with active spermatogenesis were compared. 414 genes in the caput epididymides were differentially regulated in infertile men by at least a 2-fold change as compared to the fertile men. Experiment Overall Design: Comparative caput epididymal gene expression from 4 patients with either active spermatogenesis (reference samples) or non-obstructive azoospermia. On each array, infertile tissue were compared to fertile tissue. Whenever the fertile tissues were labeled with cyanine 5 (see samples entitled "Patients 1 and 2" and "Patients 7 and 8"), the fluorescence ratios were swapped. Data was normalized using a locally weighted regression Lowess method and genes were considered differentially expressed in infertile sample versus fertile sample if there was at least a 2-fold change in 3 patients out of 4.

2008-06-16 | E-GEOD-9194 | biostudies-arrayexpress

The gene expression analysis of paracrine/autocrine factors in patients with spermatogenetic failure compared to normal spermatogenesis

Project description:The role of paracrine/autocrine factors in inflammation, immune response and tumor development is well established. There is also an evidence that some of the cytokines there involved may participate in the regulation of the male gonads. However, their involvement in pathogenesis of male infertility has not been well defined yet. The aim of the present study was to examine the expression levels of IL-1 family members, IL-6, IL-10, TNF family, SCF and c-kit in infertile patients with idiopathic non-obstructive azoospermia (NOA) compared to men with normal spermatogenesis We analyzed testicular biopsy specimens obtained from 16 patients with non-obstructive azoospermia (NOA) and 4 with normal spermatogenesis using Affymetrix Human Gene 1.0 ST.

2013-08-02 | E-GEOD-45887 | biostudies-arrayexpress

High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism

Project description:Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodelled during spermatogenesis. While high dose folic acid supplementation (up to ten times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of six months of high dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR. Reduced representation bisulfite sequencing of 28 human sperm samples before and after 6 month of high dose folic acid supplementation.

2015-09-10 | E-GEOD-72606 | biostudies-arrayexpress

Systematic characterization of seminal plasma piRNAs as molecular biomarkers for male infertility

Project description:Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technology was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in the infertile patient groups compared with the control group. Next, a quantitative RT-PCR assay was conducted in the training and validation sets to measure and confirm the concentrations of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in the seminal plasma of infertile patients compared with healthy controls. The areas under the ROC curves for these piRNAs ranged from 0.796 to 0.996, suggesting that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiological clues that are involved in the development of infertility. Fresh samples were collected and stored at -80â??.Total RNA of seminal plasma were extracted and solexa sequencing was performed.

2016-06-28 | E-GEOD-78131 | biostudies-arrayexpress

Systematic characterization of seminal plasma piRNAs as molecular biomarkers for male infertility

2016-06-28 | GSE78131 | GEO

The gene expression analysis of paracrine/autocrine factors in patients with spermatogenetic failure compared to normal spermatogenesis

2013-08-02 | GSE45887 | GEO

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing.

Project description:The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. Here we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.

2020-06-18 | PXD019087 | Pride

Characterization of genome-methylome interactions in 22 nuclear pedigrees

Project description:In this study, we investigated the interaction between CpG methylation and genetic polymorphisms by taking the advantage of the family structure in 22 nuclear pedigrees. We have identified CpG sites that exhibit heritable methylation patterns, among which the majority are SNPs ditrectly disrupting CpG dinucleotides. We also identified 27.2% of the heritable non-SNP CpGs were associated with cis-regulatory SNPs. Additionally, we have identified hundreds of CpG clusters whose the degree of DNA methylation variation is associated with genetic polymorphism. Investigate the influence of genetic variances on blood DNA methylation patterns in the human genome of 96 subjects from 22 pedigrees by using different approaches, including mid-parent offspring analysis (MPO), methylation quantitative trait loci (mQTL) analysis and allele-specific DNA methylation (ASM) Raw data not provided since the files contain genetic information of the human subject that should be protected.

2013-06-20 | E-GEOD-47614 | biostudies-arrayexpress

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