Sperm Global DNA Methylation (SGDM) in Semen of Healthy Dogs.
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ABSTRACT:
SUBMITTER: Galdiero G
PROVIDER: S-EPMC8002840 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE: Methylation of sperm DNA is impaired in many infertile men potentially adversely effecting reproductive outcomes. In somatic cells oxidative damage to DNA and hyperhomocysteinaemia are linked with DNA hypomethylation. The objective of this study was to investigate if these pathologies also impair sperm DNA methylation. METHODS: The relationship between sperm DNA quality, oxidative stress and serum homocysteine was analysed at study entry and after 3 months of antioxidant treatment. RESULTS: Overall a significant negative correlation was observed between sperm DNA methylation and sperm DNA fragmentation, as well as seminal reactive oxygen species (ROS) production. Sperm DNA methylation was not significantly related to serum homocysteine concentrations. Administration of an antioxidant supplement produced a significant fall in seminal ROS levels and sperm DNA fragmentation, while increasing sperm DNA methylation. CONCLUSIONS: These results suggest that oxidative stress related damage to sperm DNA impedes the process of methylation, while antioxidant supplementation appears to have the potential to reduce DNA damage and normalize sperm DNA methylation.
| S-EPMC2788683 | biostudies-other
Project description:Non-Hodgkin lymphomas are among the most common types of tumors in dogs, and they are currently accepted as comparative models of the disease in humans. Aberrant patterns of DNA methylation seem to play a key role in the development of hematopoietic neoplasms in humans, constitute a special mechanism of transcriptional control, and may be influenced by genetic and environmental factors. Blood leukocyte DNA global methylation has been poorly investigated in dogs. The aim of this study is to examine whether peripheral blood global DNA methylation is associated with canine multicentric lymphomas. Peripheral venous blood samples from ten healthy dogs and nine dogs bearing multicentric lymphomas were collected, and the buffy coat was separated. Global DNA methylation was analyzed by High Performance Liquid Chromatography (HPLC) and immunocytochemistry (ICC). In both analyses, leukocytes from dogs with lymphoma presented lower global DNA methylation than in healthy dogs (HPLC: p = 0.027/ 5MeCyt immunoreactivity scores: p = 0.015). Moderate correlation was observed between the results obtained by HPLC and ICC (correlation coefficient = 0.50). For the identification of differently methylated genes between both groups, the Infinium Human Methylation (HM) EPIC BeadChip (850K) was used. Of the 853,307 CpGs investigated in the microarray, there were 34,574 probes hybridized in the canine samples. From this total, significant difference was observed in the methylation level of 8433 regions, and through the homologous and orthologous similarities 525 differently methylated genes were identified between the two groups. This study is pioneer in suggesting that dogs bearing non-Hodgkin lymphoma presented DNA global hypomethylation of circulating leukocytes compared with healthy dogs. Although canine samples were used in an assay developed specifically for human DNA, it was possible to identify differently methylated genes and our results reiterate the importance of the use of peripheral blood leukocytes in cancer research and possible new biomarkers targets.
| S-EPMC6433272 | biostudies-literature
Project description:BackgroundAltered sperm DNA methylation patterns of imprinted genes as well as certain spermatogenesis-related genes has been proposed as a possible mechanism of male subfertility. Some reports suggest that there is an elevated risk of congenital diseases, associated with imprinted genes, in children conceived via intra-cytoplasmic sperm injection, due to the involvement of spermatozoa with aberrant imprinted genes obtained from infertile men.MethodsIn this study, the DNA methylation status of the promoter regions of six imprinted genes, namely potassium voltage-gated channel subfamily Q member 1 (KCNQ1), maternally expressed gene 3 (MEG3), insulin-like growth factor 2 (IGF-2), KCNQ1 overlapping transcript 1 (KCNQ1OT1), mesoderm specific transcript (MEST), and paternally expressed gene 3 (PEG3), were detected by a next generation sequencing-based multiple methylation-specific polymerase chain reaction analysis of sperm samples obtained from 166 men who sought fertility evaluation in our Reproductive Medicine Center. Thereafter, the semen samples were classified into subgroups according to sperm motility and DNA integrity status.ResultsAs compared to the normozoospermic group, the samples of the asthenospermic group exhibited significant hypermethylation in two CpG sites of IGF-2 and significant hypomethylation in one CpG site of KCNQ1 as well as three CpG sites of MEST (P < 0.05). However, we did not observe any significant differences in the overall methylation levels of these six imprinted genes (P > 0.05). Additionally, we found that 111 of 323 CpG sites were hypomethylated in the group with DNA fragmentation index (DFI) ≥ 30% as compared to the group with DFI < 30% (P < 0.05). In this case, there were significant differences in the overall methylation levels of MEG3, IGF-2, MEST, and PEG3 (P < 0.05), but not in that of KCNQ1OT1 and KCNQ1 (P > 0.05). Hence, aberrant methylation patterns of imprinted genes were more prevalent in males with poor sperm quality, especially in those with severe sperm DNA damage.ConclusionIn conclusion, abnormal DNA methylation of some CpG sites of imprinted genes are associated with poor sperm quality, including asthenospermia and severe sperm DNA impairment.
| S-EPMC9647922 | biostudies-literature
Project description:Male infertility might be clearly associated with aberrant DNA methylation patterns in human spermatozoa. An association between oxidative stress and the global methylation status of the sperm genome has also been suggested. The aim of the present study was to determine whether the global sperm DNA methylation status was affected in the spermatozoa of carriers of chromosome structural aberrations. The relationships between the 5-methylcytosine (m 5 C) levels in spermatozoa and chromatin integrity status were evaluated. The study patients comprised male carriers of chromosome structural aberrations with reproductive failure (n = 24), and the controls comprised normozoospermic sperm volunteers (n = 23). The global m 5 C level was measured using thin-layer chromatography (TLC) and immunofluorescence (IF) techniques. The sperm chromatin integrity was assessed using aniline blue (AB) staining and TUNEL assay. The mean m 5 C levels were similar between the investigated chromosome structural aberrations carriers (P) and controls (K). However, sperm chromatin integrity tests revealed significantly higher values in chromosomal rearrangement carriers than in controls (P < 0.05). Although the potential relationship between sperm chromatin integrity status and sperm DNA fragmentation and the m 5 C level juxtaposed in both analyzed groups (P vs K) was represented in a clearly opposite manner, the low chromatin integrity might be associated with the high hypomethylation status of the sperm DNA observed in carriers of chromosome structural aberrations.
| S-EPMC5227660 | biostudies-literature
Project description:Aims. We describe a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify and compare simultaneously global methylation and hydroxymethylation in human DNA of different tissues. Materials and Methods. Blood and saliva DNA from fourteen volunteers was processed for epigenetic endpoints using LC-MS/MS and PCR-pyrosequencing technology. Results. Global DNA methylation was significantly lower in saliva (mean 4.61%?±??0.80%), compared to blood samples (5.70%?±?0.22%). In contrast, saliva (0.036%?±?0.011%) revealed significantly higher hydroxymethylation compared to blood samples (mean 0.027%?±?0.004%). Whereas we did not find significant correlations for both epigenetic measures between the tissues, a significant association was observed between global methylation and global hydroxymethylation in saliva DNA. Neither LINE-1 nor Alu elements of blood and saliva correlated, nor were they correlated with the DNA hydroxymethylation of blood or saliva, respectively. Conclusion. Global DNA methylation and hydroxymethylation of cytosine can be quantified simultaneously by LC-MS/MS. Saliva DNA cannot be considered as a surrogate for blood DNA to study epigenetic endpoints.
| S-EPMC4450276 | biostudies-other
Project description:Research questionTo examine associations between sperm mitochondrial DNA copy number (mtDNAcn), sperm mitochondrial DNA deletions (mtDNAdel), semen parameters and clinical infertility in an IVF setting.DesignA total of 125 sperm samples were collected from men undergoing assisted reproductive procedures in an IVF clinic in Western Massachusetts, USA. Sperm mtDNAcn and mtDNAdel were measured by probe-based quantitative polymerase chain reaction. Semen parameters, clinical diagnoses of infertility, and infertility based on consecutive semen parameters, were fitted with mtDNAcn and mtDNAdel in linear models. The utility of sperm mtDNAcn and mtDNAdel to predict infertility was assessed by receiver operating characteristic curves.ResultsAdjusting for relevant covariates, both sperm mtDNAcn and mtDNAdel were associated with lower sperm concentration, count, motility and morphology (P ≤ 0.03). Sperm mtDNAcn and mtDNAdel were also associated with increased risks of clinical infertility based on current and consecutive semen samples. Sperm mtDNAcn had high predictive accuracy for consecutive diagnoses of clinical infertility (C-statistic: 0.91), whereas sperm mtDNAdel had moderate predictive accuracy (C-statistic: 0.75).ConclusionsSperm mtDNAcn is a measure of consecutive abnormal semen parameters and has promise as a diagnostic test.
| S-EPMC6339832 | biostudies-literature
Project description:ObjectiveTo evaluate the relationship between epigenetic patterns in sperm and fecundity.DesignProspective study.SettingAcademic andrology and in vitro fertilization laboratory.Patient(s)Twenty-seven semen samples from couples who conceived within 2 months of attempting a pregnancy and 29 semen samples from couples unable to achieve a pregnancy within 12 months.Intervention(s)None.Main outcome measure(s)Genomewide assessment of differential sperm DNA methylation and standard semen analysis.Result(s)We analyzed DNA methylation alterations associated with fecundity in 124 semen samples, and identified regions of interest in 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the human methylation 450k array analysis we did identify two genomic regions with statistically significantly decreased (false discovery rate <0.01) methylation and three genomic regions with statistically significantly increased methylation in the failure-to-conceive group. The only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B.Conclusion(s)Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.
| S-EPMC4890464 | biostudies-literature
Project description:The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.
| S-EPMC4693469 | biostudies-other
Project description:DNA methylation provides a pivotal layer of epigenetic regulation in eukaryotes that has significant involvement for numerous biological processes in health and disease. The function of methylation of cytosine bases in DNA was originally proposed as a "silencing" epigenetic marker and focused on promoter regions of genes for decades. Improved technologies and accumulating studies have been extending our understanding of the roles of DNA methylation to various genomic contexts including gene bodies, repeat sequences and transcriptional start sites. The demand for comprehensively describing DNA methylation patterns spawns a diversity of DNA methylation profiling technologies that target its genomic distribution. These approaches have enabled the measurement of cytosine methylation from specific loci at restricted regions to single-base-pair resolution on a genome-scale level. In this review, we discuss the different DNA methylation analysis technologies primarily based on the initial treatments of DNA samples: bisulfite conversion, endonuclease digestion and affinity enrichment, involving methodology evolution, principles, applications, and their relative merits. This review may offer referable information for the selection of various platforms for genome-wide analysis of DNA methylation.
| S-EPMC7914139 | biostudies-literature
Project description:BackgroundEstimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals.MethodsIndividual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing.ResultsAge [? = -0.011% of 5-methyl-cytosine (%5 mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5 mC/year] and alcohol drinking (? = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (? = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (? = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (? = 0.036, 95% CI 0.010 to 0.061) and negative (? = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively.ConclusionsGlobal methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes.
| S-EPMC3304518 | biostudies-literature