Air pollution appears to alter how sperm genes function, one of the largest fertility studies of its kind has found. Men exposed to common outdoor pollutants during the period when their sperm were developing showed subtle DNA changes affecting whether genes were switched on or off, researchers reported at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) in London.
The study, presented July 7 and published as an abstract in Human Reproduction, followed more than 2,000 men in Salt Lake City, Utah, between 2013 and 2017, tracking their exposure to four outdoor air pollutants: ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and fine particulate matter (PM2.5). Among 1,220 men who provided a six-month follow-up sample, researchers identified 39 DNA methylation changes, chemical modifications that regulate gene activity without altering the underlying DNA sequence, in sperm.
Of the four pollutants studied, ozone and nitrogen dioxide showed the strongest associations. Both are common in urban areas, produced largely by traffic emissions and natural gas combustion.
The GNAS finding
Among the most significant results was a methylation change in GNAS, an imprinted gene. Imprinted genes are expressed in a parent-of-origin-specific manner, one copy is silenced based on whether it came from the mother or father, and unlike most epigenetic marks, which are erased after fertilization, imprinted gene methylation patterns can persist through early embryonic development.
“The association with changes in the imprinted gene GNAS was particularly important,” said Dr. Carrie Nobles, the study’s lead author and an assistant professor of environmental health sciences at the University of Massachusetts Amherst. “Because imprinted genes can persist through early embryonic development, this raises important questions about whether fathers’ environmental exposures may influence not only fertility, but pregnancy and offspring health.”
The methylation changes were linked to genes involved in spermatogenesis (sperm development), chromosomal organization, and cellular quality control.
Caveats
The study has important limitations. It is a conference abstract, peer-reviewed for acceptance at the meeting but not yet published as a full paper. The analysis was conducted in a single geographic location (Salt Lake City), and the researchers used outdoor air quality monitoring data rather than personal exposure measurements. The clinical significance of the methylation changes for fertility, pregnancy, or offspring health has not been directly established.
As Prof. Allan Pacey, professor of andrology at the University of Manchester, noted in an expert reaction: “It is not possible to conclude whether the observed changes to sperm DNA methylation are clinically meaningful for male infertility. Further work will need to be done to confirm or refute that.”
Prof. Dr. Karen Sermon, immediate past chair of ESHRE, put the findings in broader context: “This is another piece of the puzzle to understand how pollution negatively influences our fertility. We know that couples exposed to air pollution often have difficulties becoming pregnant, and this may be one of the explanations.”
The researchers say replication in other populations is needed, as well as studies that directly link the observed methylation changes to measurable fertility outcomes.