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.

Prior research has shown that interruptions lead to a variety of performance costs. However, these costs are heterogenous and poorly understood. Under some circumstances, interruptions lead to large decreases in accuracy on the primary task, whereas in others task duration increases, but task accuracy is unaffected. Presently, the underlying cause of these costs is unclear. The Memory for Goals model suggests that interruptions interfere with the ability to represent the current goal of the primary task. Here, we test the idea that working memory (WM) may play a critical role in representing the current goal and thus may underlie the observed costs associated with interruption. In two experiments, we utilized laboratory-based visual search tasks, which differed in their WM demands, in order to assess how this difference influenced the observed interruption costs. Interruptions led to more severe performance costs when the target of the search changed on each trial. When the search target was consistent across trials, the cost of interruption was greatly reduced. This suggests that the WM demands associated with the primary task play an important role in determining the performance costs of interruption. Our findings suggest that it is important for research to consider the cognitive processes a task engages in order to predict the nature of the adverse effects of interruption in applied settings such as radiology.

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Paternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. Here we use mouse models to investigate mechanisms and impacts of paternal CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking is associated with changes in prefrontal cortex DNAme and gene expression patterns in offspring. Remarkably, the epigenetic and transcriptional effects of CS exposure that we observed in wild type mice are partially recapitulated in Nrf2-/mice and their offspring, independent of smoking status. Nrf2 is a central regulator of antioxidant gene transcription, and mice lacking Nrf2 consequently display elevated oxidative stress, suggesting that oxidative stress may underlie CS-induced heritable epigenetic changes. Importantly, paternal sperm DNAme changes do not overlap with DNAme changes measured in offspring prefrontal cortex, indicating that the observed DNAme changes in sperm are not directly inherited. Additionally, the changes in sperm DNAme associated with CS exposure were not observed in sperm of unexposed offspring, suggesting the effects are likely not maintained across multiple generations.

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