Professor Paul Lewis

Much of the research data on air pollutant-induced DNA damage and resulting mutation profiles in oocytes and sperm have been generated in animal models. Whereas such data provide valuable insight into mutagenic mechanisms it is possible that mutation profiles in humans might differ to some extent. DNA adducts, especially from polycyclic aromatic hydrocarbons (PAHs) and reactive VOC metabolites, frequently target guanine bases, causing G T transversions and G  A transitions where mutations linked to oxidative stress and rep- lication errors (Zhang et al., Sci Total Environ, 2018). In sperm, these mutations often affect genes critical for chromatin packaging, such as PRM1 and PRM2, resulting in defective condensation and impaired motility. Damage to DNA repair genes like OGG1 and XRCC1 further exacerbates mutation accumulation (Lee et al., Ecotoxicol Environ Saf, 2024). In oocytes, exposure disrupts meiosis, increasing the risk of aneuploidy and mutations in mitochondrial genes (ND5, COX1), which are essential for early embryo development.

The likelihood of a bulky DNA adduct forming, typical of a PAH, can be dependent on certain primary DNA sequences and resulting secondary structures that facilitate mutagen binding (Menzies et al., NAR , 2015). Additionally, both PM₂.₅ and VOCs can alter epigenetic processes, including DNA methylation of key fertilityrelated genes like HOXA10 and GDF9, and dysregulate miRNAs such as miR-34c and miR-21, which govern gametogenesis (NHANES, Sci Rep, 2024). These genetic and epigenetic changes reduce gamete viability and increase risks of miscarriage and heritable disorders, highlighting the reproductive toxicity of ambient air pollution (WHO, 2023; Prague Study, 2009).

DNA structural change is not just limited to somatic cells. Epigenetic dysregulation in germline cells, through methylation changes and miRNA disruption, can add a heritable dimension to this damage, raising concern for transgenerational effects on offspring health and viability (Spanou, 2025). These mutations and epimutations may not only impair conception and embryonic development but also silently propagate heritable risks through generations.

About Professor Paul Lewis. He is Chief Scientific Officer, Raven Delta Group Ltd., Professor Emeritus, Medical School, Swansea University, Clean Air Programme, Regional Champion for Wales, Welsh Government Chair of Clean Air Advisory Panel