Air pollution associated epigenetic modifications: Transgenerational inheritance and underlying molecular mechanisms.

Air pollution is one of the leading causes of deaths in Southeast Asian countries including India. Exposure to air pollutants affects vital cellular mechanisms and is intimately linked with the etiology of a number of chronic diseases. Earlier work from our laboratory has shown that airborne particulate matter disturbs the mitochondrial machinery and causes significant damage to the epigenome. Mitochondrial reactive oxygen species possess the ability to trigger redox-sensitive signaling mechanisms and induce irreversible epigenomic changes. The electrophilic nature of reactive metabolites can directly result in deprotonation of cytosine at C-5 position or interfere with the DNA methyltransferases activity to cause alterations in DNA methylation. In addition, it also perturbs level of cellular metabolites critically involved in different epigenetic processes like acetylation and methylation of histone code and DNA hypo or hypermethylation. Interestingly, these modifications may persist through downstream generations and result in the transgenerational epigenomic inheritance. This phenomenon of subsequent transfer of epigenetic modifications is mainly associated with the germ cells and relies on the germline stability of the epigenetic states. Overall, the recent literature supports, and arguably strengthens, the contention that air pollution might contribute to transmission of epimutations from gametes to zygotes by involving mitochondrial DNA, parental allele imprinting, histone withholding and non-coding RNAs. However, larger prospective studies using innovative, integrated epigenome-wide metabolomic strategy are highly warranted to assess the air pollution induced transgenerational epigenetic inheritance and associated human health effects.