Tissue Specific Age Acceleration in the Sperm of Oligozoospermic Men
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ABSTRACT:
PROVIDER: PRJNA880607 | ENA |
REPOSITORIES: ENA
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Project description:To determine if disease can modify aging patterns in an affected tissue without altering the aging patterns of other tissues, blood and semen of individuals with oligozoospermia (n=10) were compared to the blood and semen of individuals with normozoospermia (n=24). The Horvath and Jenkins age calculators were utilized to predict the epigenetic age of blood and sperm through the use of DNA methylation. Using these calculators, it was found that sperm of oligozoospermic men were predicted to be significantly older than the sperm of normozoospermic men; however, there was not a significant epigenetic age difference in blood. These results lead to the conclusion that tissue specific aging is occurring in sperm of oligozoospermic individuals but not in unaffected somatic tissues (in our case, blood).
2023-09-08 | GSE213366 | GEO
Project description:To determine if disease can modify aging patterns in an affected tissue without altering the aging patterns of other tissues, blood and semen of individuals with oligozoospermia (n = 10) were compared to the blood and semen of individuals with normozoospermia (n = 24). DNA methylation data was obtained via Illumina's 850 K array. The Horvath and Jenkins age calculators were then utilized to predict the epigenetic age of blood and sperm. Epigenetic age of sperm was approximated using germ-line age differential (GLAD) values. Using nonpaired t-tests, it was found that sperm of oligozoospermic men (mean GLAD score of 0.078) were predicted to be significantly older than the sperm of normozoospermic men (mean GLAD score of -0.017), returning a p-value of 0.03. However, there was not a significant epigenetic age difference between the blood of those with oligozoospermia (mean GLAD equivalent score of -0.027) and normozoospermia (mean GLAD equivalent score of 0.048), producing a p-value of 0.20. These results lead to the conclusion that tissue specific aging is occurring in sperm of oligozoospermic individuals but not in unaffected somatic tissues (in this case, blood).
| S-EPMC9727134 | biostudies-literature
Project description:Protamine1 (P1) and Protamine 2 family (P2) are the most relevant nuclear proteins in the male gamete since are necessary to compact and protect the paternal genome. Human and mouse sperm contain a complex population of protamine proteoforms, which raises the interest to decipher whether it responds to a need of protein redundancy to ensure proper chromatin compaction, or whether specific protamine proteoforms have functional implications. In this study, we apply an optimized strategy based on Top-Down Mass Spectrometry to quantify alterations in the protamine proteoform profile of normozoospermic men with unexplained infertility and either molecular (high P1/P2) or lifestyle (obesity and advanced age) alterations. Accumulation of P2 immature forms was associated to higher P1/P2 ratios, suggesting an impaired processing of P2 in these patients. Men with obesity and intracellular oxidative stress revealed alterations in P1 proteoforms with mass shift(s) of +61 Da, either phosphorylated or not, and advanced age men showed a specific loss of diphosphorylated P1. These results point to alterations on protamine modifying mechanisms, such as proteolysis and phosphorylation, rather than on protamine synthesis, as critical factors for proper sperm chromatin maturity with impact on male fertility
2025-04-25 | PXD049367 | Pride
Project description:The objective of this study was to provide a comprehensive assessment of protamine isoforms and modifications in human sperm with the aim of identifying how protamine modifications/isoforms are altered in men with reduced sperm motility and low sperm count. Sperm samples from 18 men with prior reported pregnancy and normozoospermia 14 men from couples with infertility and asthenozoospermia and 24 men from couples with infertility and oligoasthenoteratozoospermia were included in the study. Proteomic assessment using both top-down and bottom-up LC-MS was performed.
2025-05-06 | PXD046041 | Pride
Project description:Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronological age (CA), has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the rise in early onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of pre-neoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation (DNAm) at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 17% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the rise in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model.
2024-12-11 | GSE282666 | GEO
Project description:To answer the question of whether preconception phthalate and phthalate replacements associated with sperm differentially methylated regions (DMRs) among men undergoing in-vitro fertilization, genome-wide DNA-methylation profiles of 48 human sperm samples were generated by bisulfite-based Illumina 450K BeadChip arrays. The sperm DNA methylation is then correlated with urinary phthalate metabolite concentrations.
2017-10-01 | GSE102970 | GEO
Project description:Background: Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches. Results: Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to two to three years post-treatment, when compared to the CC cohort. Similarly, a higher resolution human sperm-specific assay that includes assessment of environmentally-sensitive regions, or “dynamic sites”, also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites. Conclusions: Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to two years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health."
2023-01-25 | GSE211121 | GEO
Project description:Background: Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches. Results: Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to two to three years post-treatment, when compared to the CC cohort. Similarly, a higher resolution human sperm-specific assay that includes assessment of environmentally-sensitive regions, or “dynamic sites”, also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites. Conclusions: Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to two years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.
2023-01-25 | GSE211120 | GEO
Project description:In the present study, we analyzed the proteome profile of Simmental bull sperm using LC-MS/MS. We found that the proteomes in sperm varied significantly between age groups, with some proteins found only in the older age group and not in the productive age group (young) and vice versa.
2024-07-31 | PXD054403 | JPOST Repository
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