Inter- and transgenerational epigenetic inheritance: evidence in asthma and COPD?

Abstract

Evidence is now emerging that early life environment can have lifelong effects on metabolic, cardiovascular, and pulmonary function in offspring, a concept also known as fetal or developmental programming. In mammals, developmental programming is thought to occur mainly via epigenetic mechanisms, which include DNA methylation, histone modifications, and expression of non-coding RNAs. The effects of developmental programming can be induced by the intrauterine environment, leading to intergenerational epigenetic effects from one generation to the next. Transgenerational epigenetic inheritance may be considered when developmental programming is transmitted across generations that were not exposed to the initial environment which triggered the change. So far, inter- and transgenerational programming has been mainly described for cardiovascular and metabolic disease risk. In this review, we discuss available evidence that epigenetic inheritance also occurs in respiratory diseases, using asthma and chronic obstructive pulmonary disease (COPD) as examples. While multiple epidemiological as well as animal studies demonstrate effects of ‘toxic’ intrauterine exposure on various asthma-related phenotypes in the offspring, only few studies link epigenetic marks to the observed phenotypes. As epigenetic marks may distinguish individuals most at risk of later disease at early age, it will enable early intervention strategies to reduce such risks. To achieve this goal further, well designed experimental and human studies are needed.

Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study

“…Emerging findings have been pointed out that epigenetic mechanisms exert a pivotal role in COPD physiopathology (Krauss-Etschmann et al, 2015). Epigenetic has been defined as dynamic regulation of gene expression in response to external stimuli independent that is independent of changes in the underlying DNA sequence.…”

Dose- and time- effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution

“…Previous studies have already demonstrated global hypomethylation and hypermethylation of tumor suppressor genes in lung cancer patients, which could be rescued by effective treatments1415. Other studies have also revealed abnormal DNA methylation status in patients with asthma161718 and COPD1920. In addition, abnormal histone acetylation (for instance, H3K9ac, H3K18ac, and H4K16ac), which could be rescued by effective treatments, is also associated with respiratory diseases212223.…”

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring

“…However, we observed a stronger impact of parental BHR and IgEs measured before conception, suggesting that parental preconception disease activity in itself might affect respiratory health in offspring. Based on newly observed epigenetic inheritance in animal models and our findings, we hypothesize that ongoing respiratory and allergic disease activity in humans might cause epigenetic changes that can be inherited to the next generation, manifesting phenotypic characteristics in the offspring. Although this is biologically plausible given experimental research results , this has not been described in humans to date.…”