Uncovering the effects of early life cigarette smoke exposure on offspring lung function and DNA methylation patterns using a mouse model
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Date
2024-10-30
Authors
Onuzulu, Chinonye (Doris)
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Abstract
Early life cigarette smoke (CS) exposure has been associated with the development of sex-specific, persistent health deficits in offspring, and changes in epigenetic marks such as DNA methylation (DNAm) potentially link early life CS to these health outcomes. There is also evidence that addition of a secondary CS exposure in adulthood further exacerbates these health alterations, a process known as priming. However, while past studies have identified DNAm patterns which are altered following early life CS, the impacts of prenatal and early postnatal CS have not been studied separately, most of the past research was conducted in blood with little evidence from the lungs and other more proximal tissues, and DNAm patterns underlying sex-specific health outcomes have not been investigated. In addition, the molecular mechanisms underlying priming upon combined early and later life CS have not been reported. Using a mouse model which we developed to separately study the effects of prenatal, early postnatal, or combined CS exposure on offspring lung function and DNAm, we uncovered differentially methylated sites and lung function phenotypes which are unique to each type of CS exposure, with minimal overlaps across groups, across tissues and between sexes. We also identify DNAm alterations which persist into adulthood following early life CS, identifying a period in adulthood where the effects of early life CS exposure are most pronounced. Our results also demonstrate for the first time, epigenetic priming in mice following repeated CS exposure, and we identify novel biomarkers specific to prenatal CS exposure and smoking in adulthood. Overall, this research offers deeper insights into the molecular mechanisms underlying early life CS-induced phenotypes, as this understanding is important to the development of intervention strategies to mitigate the effects of early life CS exposure on offspring health.
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Keywords
Cigarette smoke, DNA methylation, Early life, Priming, Lung function