Cigarette smoking significantly alters sperm DNA methylation patterns

Abstract

Numerous health consequences of tobacco smoke exposure have been characterized, and smoking’s effects on traditional measures of male fertility are well described. However, a growing body of data indicates that pre-conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through sperm. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never-smokers using the Infinium HumanMethylation450 beadchip. We investigated two models of DNA methylation alterations: (1) consistently altered methylation at specific CpGs or within specific genomic regions and (2) stochastic DNA methylation alterations manifest as increased variability in genome-wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome-wide in sperm DNA from men who smoke compared with never-smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre-conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.

Paternal germ line aging: DNA methylation age prediction from human sperm

“…Individuals with many different fertility phenotypes provided the samples used in this study. Specifically, our training data set includes samples from sperm donors [2], known fertile individuals, infertility patients (including those seeking intrauterine insemination or even in vitro fertilization treatment at our facility), and individuals from the general population [6,7].…”

“…To test the potential diagnostic/clinical utility of our model we have more closely assessed the data in our original cross validation dataset. Specifically we have analyzed our smoking dataset [7], which includes sperm methylation data from 78 smokers and 78 individuals who responded as "never smokers." Similar aged men are represented in each group.…”

“…In the current study we assessed sperm DNA methylation array data (Illumina 450K array) from 3 distinct previously performed studies [2,6,7]. From these data sets, we were able to acquire a total of 329 samples that were used to generate the predictive model outlined herein.…”

“…To determine the drivers of the age-associated change in these regions, we examined the level of variability/instability of methylation signals between the individual's screened in our test/training set. We assessed the methylation variability between individuals at each of these sites by methods we have previously described [7]. Using these techniques we binned individuals by year of age and then generated measures of variation within each bin (to avoid the increased levels of variation that would be present simply due to the change with age we have identified).…”

Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure

“…Smoking has been clearly shown to modify DNAme patterns and gene expression in somatic tissues in individuals exposed to first-or second-hand tobacco smoke (Kohli et al, 2012, Bosse et al, 2012, Word et al, 2012 as well as in newborns of smoking mothers (Breton et al, 2009, Perera and Herbstman, 2011. We recently reported altered sperm DNA methylation (DNAme) patterns in men who smoke (Jenkins et al, 2017).…”