Impact of cigarette-smoking on sperm DNA methylation and its effect on sperm parameters

Alkhaled, Y.; Laqqan, Mohammed M.; Tierling, Sascha; Porto, Christina Lo; Amor, Houda; Hammadeh, Mohamad Eid

doi:10.1111/and.12950

Cited by 26 publications

(22 citation statements)

References 85 publications

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“…It was also in a different region of the gene (chr16:1813414 versus chr16:1797050). Alkhaled et al [33]. identified differential methylation of PGAM5, PTPRN2 and TYRO3 comparing sperm DNA methylation of smokers to non-smokers.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid exposure and altered DNA methylation in rat and human sperm

et al. 2018

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Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicleexposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.

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Section: Discussionmentioning

confidence: 99%

Cannabinoid exposure and altered DNA methylation in rat and human sperm

et al. 2018

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“…With this approach, various factors including age (Jenkins et al. 2014), smoking (Alkhaled et al. 2018; Jenkins et al.…”

Section: Introductionmentioning

confidence: 99%

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism

Chan

Shao

Dumargne

et al. 2019

Environ Health Perspect

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Background:The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.Objectives:Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.Methods:To characterize variation in sperm DNA methylation, we performed whole genome bisulfite sequencing (WGBS) on an equimolar pool of sperm DNA from a wide cross section of 30 men varying in age, fertility status, methylenetetrahydrofolate reductase (MTHFR) genotype, and exposures. With our targeted capture panel, in individual samples, we examined the effect of MTHFR genotype (n=13 677CC, n=8 677TT), as well as high-dose folic acid supplementation (n=6, per genotype, before and after supplementation).Results:Through WGBS we discovered nearly 1 million CpGs possessing intermediate methylation levels (20–80%), termed dynamic sperm CpGs. These dynamic CpGs, along with 2 million commonly assessed CpGs, were used to customize a capture panel for targeted interrogation of the human sperm methylome and test its ability to detect effects of altered folate metabolism. As compared with MTHFR 677CC men, those with the 677TT genotype (50% decreased MTHFR activity) had both hyper- and hypomethylation in their sperm. High-dose folic acid supplement treatment exacerbated hypomethylation in MTHFR 677TT men compared with 677CC. In both cases, >80% of altered methylation was found in dynamic sperm CpGs, uniquely measured by our assay.Discussion:Our sperm panel allowed the discovery of differential methylation following conditions affecting folate metabolism in novel dynamic sperm CpGs. Improved ability to examine variation in sperm DNA methylation can facilitate comprehensive studies of environment–epigenome interactions. https://doi.org/10.1289/EHP4812

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“…Nineteen studies investigated the effect of various toxicants on spermatozoal DNA methylation, including six studies of cigarette smoke (Kim et al, 2015;Jenkins et al, 2017;Laqqan et al, 2017c;Al Khaled et al, 2018;Alkhaled et al, 2018;Hamad et al, 2018), two studies of recreational drugs (cannabis and opioids) (Chorbov et al, 2011;Murphy et al, 2018) and four studies of organic pollutants such as mercury, polycyclic aromatic hydrocarbons (PAHs), per-and polyfluoroalkyl substances and phthalate metabolites (Leter et al, 2014;Wu et al, 2017;Lu et al, 2018;Ma et al, 2019;Tian et al, 2019). Among these, the quality of evidence was scored as high for three studies, moderate for 10, low for five and very low for one study (Table III).…”

Section: Toxicantsmentioning

confidence: 99%

DNA methylation in human sperm: a systematic review

Åsenius¹,

Danson

Marzi

2020

Human Reproduction Update

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BACKGROUND Studies in non-human mammals suggest that environmental factors can influence spermatozoal DNA methylation, and some research suggests that spermatozoal DNA methylation is also implicated in conditions such as subfertility and imprinting disorders in the offspring. Together with an increased availability of cost-effective methods of interrogating DNA methylation, this premise has led to an increasing number of studies investigating the DNA methylation landscape of human spermatozoa. However, how the human spermatozoal DNA methylome is influenced by environmental factors is still unclear, as is the role of human spermatozoal DNA methylation in subfertility and in influencing offspring health. OBJECTIVE AND RATIONALE The aim of this systematic review was to critically appraise the quality of the current body of literature on DNA methylation in human spermatozoa, summarize current knowledge and generate recommendations for future research. SEARCH METHODS A comprehensive literature search of the PubMed, Web of Science and Cochrane Library databases was conducted using the search terms ‘semen’ OR ‘sperm’ AND ‘DNA methylation’. Publications from 1 January 2003 to 2 March 2020 that studied human sperm and were written in English were included. Studies that used sperm DNA methylation to develop methodologies or forensically identify semen were excluded, as were reviews, commentaries, meta-analyses or editorial texts. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used to objectively evaluate quality of evidence in each included publication. OUTCOMES The search identified 446 records, of which 135 were included in the systematic review. These 135 studies were divided into three groups according to area of research; 56 studies investigated the influence of spermatozoal DNA methylation on male fertility and abnormal semen parameters, 20 studies investigated spermatozoal DNA methylation in pregnancy outcomes including offspring health and 59 studies assessed the influence of environmental factors on spermatozoal DNA methylation. Findings from studies that scored as ‘high’ and ‘moderate’ quality of evidence according to GRADE criteria were summarized. We found that male subfertility and abnormal semen parameters, in particular oligozoospermia, appear to be associated with abnormal spermatozoal DNA methylation of imprinted regions. However, no specific DNA methylation signature of either subfertility or abnormal semen parameters has been convincingly replicated in genome-scale, unbiased analyses. Furthermore, although findings require independent replication, current evidence suggests that the spermatozoal DNA methylome is influenced by cigarette smoking, advanced age and environmental pollutants. Importantly however, from a clinical point of view, there is no convincing evidence that changes in spermatozoal DNA methylation influence pregnancy outcomes or offspring health. WIDER IMPLICATIONS Although it appears that the human sperm DNA methylome can be influenced by certain environmental and physiological traits, no findings have been robustly replicated between studies. We have generated a set of recommendations that would enhance the reliability and robustness of findings of future analyses of the human sperm methylome. Such studies will likely require multicentre collaborations to reach appropriate sample sizes, and should incorporate phenotype data in more complex statistical models.

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Impact of cigarette-smoking on sperm DNA methylation and its effect on sperm parameters

Cited by 26 publications

References 85 publications

Cannabinoid exposure and altered DNA methylation in rat and human sperm

Cannabinoid exposure and altered DNA methylation in rat and human sperm

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism

DNA methylation in human sperm: a systematic review

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