scholarly journals Age-associated sperm DNA methylation patterns do not directly persist trans-generationally

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Timothy G. Jenkins ◽  
Emma R. James ◽  
Kenneth I. Aston ◽  
Albert Salas-Huetos ◽  
Alexander W. Pastuszak ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Human Sperm ◽  
Paternal Age ◽  
Sperm Dna ◽  
Two Generations ◽  
Methylation Patterns ◽  
The Impact ◽  
Sperm Dna Methylation

Abstract Background The impact of aging on the sperm methylome is well understood. However, the direct, subsequent impact on offspring and the role of altered sperm DNA methylation alterations in this process remain poorly understood. The well-defined impact of aging on sperm DNA methylation represents an excellent opportunity to trace the direct, transgenerational transmission of these signals. Results We utilized the Illumina MethylationEPIC array to analyze the sperm of 16 patients with older (> 40 years of age) paternal grandfathers (‘old grand paternal age’ patients; OGPA) and 16 patients with younger (< 25 years of age) grandfathers (‘young grand paternal age’ patients; YGPA) identified through the Subfertility Health Assisted Reproduction and the Environment (SHARE) cohort to investigate differences in DNA methylation. No differentially methylated regions were identified between the OGPA and YGPA groups. Further, when assessing only the sites previously shown to be altered by age, no statistically significant differences between OGPA and YGPA were identified. This was true even despite the lower bar for significance after removing multiple comparison correction in a targeted approach. Interestingly though, in an analysis of the 140 loci known to have decreased methylation with age, the majority (~ 72%) had lower methylation in OGPA compared to YGPA though the differences were extremely small (~ 1.5%). Conclusions This study suggests that the robust and consistent age-associated methylation alterations seen in human sperm are ‘reset’ during large-scale epigenetic reprograming processes and are not directly inherited trans-generationally (over two generations). An extremely small trend was present between the YGPA and OGPA groups that resemble the aging pattern in older sperm. However, this trend was not significant and was so small that, if real, is almost certainly biologically inert.

scholarly journals Male obesity impacts DNA methylation reprogramming in sperm

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sanaz Keyhan ◽  
Emily Burke ◽  
Rose Schrott ◽  
Zhiqing Huang ◽  
Carole Grenier ◽  
...  
Keyword(s):  
Dna Methylation ◽  
System Development ◽  
Human Sperm ◽  
Nervous System Development ◽  
Cpg Sites ◽  
Epididymal Maturation ◽  
Sperm Dna ◽  
Stem Cell Pluripotency ◽  
The Impact ◽  
Sperm Dna Methylation

Abstract Background Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). Results We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. Conclusions Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.

Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility

2010 ◽  
Vol 94 (5) ◽  
pp. 1728-1733 ◽  
Author(s):  
Saher Sue Hammoud ◽  
Jahnvi Purwar ◽  
Christian Pflueger ◽  
Bradley R. Cairns ◽  
Douglas T. Carrell
Keyword(s):  
Dna Methylation ◽  
Sperm Dna ◽  
Methylation Patterns ◽  
Sperm Dna Methylation

scholarly journals Exposure to childhood abuse is associated with human sperm DNA methylation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Andrea L. Roberts ◽  
Nicole Gladish ◽  
Evan Gatev ◽  
Meaghan J. Jones ◽  
Ying Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Childhood Abuse ◽  
Human Sperm ◽  
Sperm Dna ◽  
Sperm Dna Methylation

scholarly journals Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations

Development ◽  
2021 ◽  
Author(s):  
Gurbet Karahan ◽  
Donovan Chan ◽  
Kenjiro Shirane ◽  
Taylor McClatchie ◽  
Sanne Janssen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylenetetrahydrofolate Reductase ◽  
Embryonic Germ Cells ◽  
Sperm Dna ◽  
Sperm Counts ◽  
F2 Generation ◽  
Successive Generations ◽  
Mthfr Deficiency ◽  
The Impact ◽  
Sperm Dna Methylation

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in the folate metabolic pathway with a key role in generating methyl groups. As MTHFR deficiency impacts male fertility and sperm DNA methylation, there is the potential for epimutations to be passed to the next generation. Here, we assessed whether the impact of MTHFR deficiency on testis morphology and sperm DNA methylation is exacerbated across generations. While MTHFR deficiency in F1 fathers has only minor effects on sperm counts and testis weights and histology, F2 generation sons show further deterioration in reproductive parameters. Extensive loss of DNA methylation is observed in both F1 and F2 sperm, with &gt;80% of sites shared between generations, suggestive of regions consistently susceptible to MTHFR deficiency. These regions are generally methylated during late embryonic germ cell development and are enriched in young retrotransposons. As retrotransposons are resistant to reprogramming of DNA methylation in embryonic germ cells, their hypomethylated state in the sperm of F1 males could contribute to the worsening reproductive phenotype observed in F2 MTHFR- deficient males, findings compatible with the intergenerational passage of epimutations.

scholarly journals Influence of tobacco cigarette heavy smoking on DNA methylation patterns and transcription levels of MAPK8IP3, GAA, ANXA2, PRRC2A, and PDE11A genes in human spermatozoa

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Mohammed M. Laqqan ◽  
Maged M. Yassin
Keyword(s):  
Dna Methylation ◽  
Semen Parameters ◽  
Global Dna Methylation ◽  
Transcription Level ◽  
Heavy Smoking ◽  
Tobacco Cigarette ◽  
Sperm Dna ◽  
Methylation Patterns ◽  
Heavy Smokers ◽  
Sperm Dna Methylation

Abstract Background Tobacco smoking is considered as one of the lifestyles factors that influence the sperm DNA methylation and global sperm DNA methylation and that may affect the sperm phenotype. This study was performed to investigate whether tobacco cigarette heavy smoking influences sperm DNA methylation patterns and semen parameters and to determine whether there is an alteration in the transcription level of MAPK8IP3, GAA, ANXA2, PRRC2A, and PDE11A genes in heavy smokers compared to non-smokers. Thirty samples were subjected to 450K arrays as a screening study to assess the variation in sperm DNA methylation levels between heavy smokers and non-smokers. Five CpG sites have the highest difference in methylation levels (cg07869343, cg05813498, cg09785377, cg06833981, and cg02745784), which are located in the MAPK8IP3, GAA, ANXA2, PRRC2A, and PDE11A genes, respectively, and were selected for further analysis using deep bisulfite sequencing in 280 independent samples (120 proven non-smokers and 160 heavy smokers) with a mean age of 33.8 ± 8.4 years. The global sperm DNA methylation, sperm DNA fragmentation, and chromatin non-condensation were evaluated also. Results A significant increase was found in the methylation level at seven, three, and seventeen CpGs within the GAA, ANXA2, and MAPK8IP3 genes amplicon, respectively (P< 0.01) in heavy smokers compared to non-smokers. Additionally, a significant increase was found in the methylation levels at all CpGs within PRRC2A and PDE11A gene amplicon (P< 0.01). A significant increase was found in the level of sperm chromatin non-condensation, DNA fragmentation, and global DNA methylation (P < 0.001) in heavy smokers compared to non-smokers. Conclusion These results indicate that tobacco cigarette smoking can alter the DNA methylation level at several CpGs, the status of global DNA methylation, and transcription level of the following genes “MAPK8IP3, GAA, ANXA2, PRRC2A, and PDE11A” in human spermatozoa. These findings may affect negatively semen parameters and men’s fertility.

scholarly journals The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Albert Salas-Huetos ◽  
Emma R. James ◽  
Dallin S. Broberg ◽  
Kenneth I. Aston ◽  
Douglas T. Carrell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Line ◽  
Age Groups ◽  
Human Sperm ◽  
Absolute Error ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Sperm Dna ◽  
Epigenetic Age Acceleration ◽  
The Impact

Abstract Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual’s age. Herein, we performed this preliminary cohort study to determine if increased BMI accelerates the epigenetic aging in sperm. A total of 96 participants were divided into four age groups (22–24, 30, 40–41, and > 48 years of age) and additionally parsed into two BMI sub-categories (normal and high/obese). We found no statistically significant epigenetic age acceleration. However, it is important to note that within each age category, high BMI individuals were predicted to be older on average than their actual age (~ 1.4 years), which was not observed in the normal BMI group. To further investigate this, we re-trained a model using only the present data with and without BMI as a feature. We found a modest but non-significant improvement in prediction with BMI [r2 = 0.8814, mean absolute error (MAE) = 3.2913] compared to prediction without BMI (r2 = 0.8739, MAE = 3.3567). Future studies with higher numbers of age-matched individuals are needed to definitively understand the impact of BMI on epigenetic aging in sperm.

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