Exposure to everyday air pollutants appears to leave a detectable mark on the molecular machinery of human sperm. That is the central finding from research presented this month at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology and published in the journal Human Reproduction.
The study examined semen samples from 1,220 men who were seeking infertility treatment. It found that mixtures of common pollutants, ozone and nitrogen dioxide in particular, were associated with 39 distinct changes in DNA methylation. Nine of these changes reached a high level of statistical confidence across eight genes, while another 30 appeared at a slightly lower threshold across 26 genes.
These alterations touched processes at the heart of sperm development. Affected genes play roles in stem cell maintenance, the differentiation of spermatogonia, chromosomal organisation, proteostasis, spermatogenesis itself, microtubule function, RNA and protein handling, lysosomal activity, and the imprinted gene GNAS. Such epigenetic shifts, the researchers note, could influence not only male fertility but also the earliest stages of new human life.
Precise measurement of exposure and outcome
Researchers estimated each man's exposure to air pollution mixtures by using the Community Multiscale Air Quality model at his residential address during the roughly three-month window of sperm development. They measured sperm DNA methylation with the Illumina EPIC version 1 array. Statistical analysis relied on quantile g-computation to assess the combined effect of pollutant mixtures, alongside linear regression for individual pollutants, with careful adjustment for age, season, temperature and trial randomisation.
The work formed an ancillary analysis of the FAZST trial, conducted between 2013 and 2017. Samples came from the six-month follow-up visit, giving a clear temporal link between ambient conditions and observed molecular changes. Ozone and nitrogen dioxide contributed most strongly to the mixture effects observed.
Exposure to air pollutant mixtures was associated with differential methylation of genes involved in stem cell maintenance, differentiation of spermatogonia, chromosomal organisation, and proteostasis.
Those are the words of lead author Dr Carrie Nobles, assistant professor in the Department of Environmental Health Sciences at the University of Massachusetts Amherst, summarising the core result in the study abstract.