Utah Cohort Links Ozone and NO2 Mixtures to 39 Sperm DNA Methylation Sites Including GNAS Imprint
Observational study of 1,220 men found air-pollution mixtures associated with sperm DNA methylation changes at 39 sites, notably GNAS. Evidence remains associative; replication and functional validation are required before causal claims about fertility or offspring outcomes can be made. Next studies must include personal exposure monitoring and longitudinal pregnancy follow-up.
The study combined repeated semen samples collected 2013-2017 with modeled outdoor pollutant exposures across the three-month spermatogenic window. Researchers applied mixture models to identify joint effects rather than single-pollutant associations, revealing ozone and NO2 as dominant contributors to methylation shifts in genes regulating sperm development and chromosomal organization. This extends earlier observational reports linking PM2.5 and traffic pollutants to reduced semen parameters by moving to an epigenetic intermediate.
Nobles et al.: Independent cohort replication within 36 months will detect GNAS methylation difference >4% in at least 70% of ozone-exposed participants.
Sources (2)
- [1]Primary Source(https://academic.oup.com/humrep/article/doi/10.1093/humrep/deaa123)
- [2]Supporting Source(https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(21)00234-5/fulltext)