Air pollution and male fertility: nitrogen dioxide and ozone alter sperm DNA methylation

If you live in a city, you breathe them every day: nitrogen dioxide and ozone, two gases now suspected of interfering with the genetic instructions that sperm carry with them to the embryo.

Worldwide, air pollution - indoors and outdoors combined - causes around 7 million premature deaths each year. People who are not killed by it may develop numerous conditions: strokes, heart attacks, hypertension, asthma, acute respiratory infections, lung cancer and neurological disorders, including cognitive decline and Alzheimer’s disease. During the 2010s, studies in andrology multiplied, and the medical community came to understand that exposure to exhaust fumes and fine particulate matter also reduces sperm concentration and motility in men.

Until the 2020s, it was known that sperm could be damaged, but the precise way these environmental assaults left a mark that could be passed on to an embryo remained unclear. Research by Dr Carrie Nobles, presented in July 2026 at the ESHRE (European Society of Human Reproduction and Embryology) congress, has now identified two suspects. Nitrogen dioxide and ozone, both widespread in the atmosphere, alter sperm DNA methylation, potentially threatening reproductive health.

Air pollution and male fertility: a dangerous connection

This is among the largest studies ever carried out on the subject. It followed more than 2,000 men from Salt Lake City, Utah, for four years, from 2013 to 2017. Participants provided a semen sample on enrolment and then again after two, four and six months. These intervals reflect the length of spermatogenesis: the roughly three-month process through which a testicular stem cell divides and develops into a functional sperm cell.

By spacing out collection in this way, the researchers obtained an entirely new generation of sperm on every occasion, produced during the weeks since the preceding sample. They then matched each sample against air-quality records covering that same period.

Nitrogen dioxide and ozone in Salt Lake City

The team examined four pollutants commonly found in urban areas: sulphur dioxide, fine particulate matter, nitrogen dioxide and ozone. Salt Lake City has particularly high concentrations because it combines heavy traffic with homes heated largely by natural gas. Burning this fuel, as well as internal-combustion engines, releases nitrogen dioxide, some of which is converted into ozone when exposed to sunlight. These two pollutants therefore dominate the city’s air, and they were specifically the ones that analysis identified as having the greatest influence on sperm DNA methylation.

Methylation is a natural biological mechanism through which a cell can silence a gene without deleting it. The cell attaches a methyl group - a small “chemical label” - which prevents proteins from accessing the sequence to read it. The gene is still present, but it is no longer expressed. A sperm cell therefore reaches the egg carrying the father’s genetic code, along with a set of labels indicating which of his genes should remain silent.

The GNAS gene and inherited methylation marks

When the researchers compared the sperm samples with pollution records, they identified 39 of these displaced labels. Only one particularly drew their attention: the label on the GNAS gene (Guanine Nucleotide-binding protein, Alpha Stimulating activity polypeptide), which operates differently from the overwhelming majority of other genes.

Its activity depends directly on which parent transmitted it. The copy inherited from the father and that inherited from the mother have different labels, with one remaining active while the other is inactive. GNAS has also appeared in other research linking sperm quality with foetal development, placing it precisely at the intersection of the study’s two concerns.

“Our findings suggest that exposure to air pollution during key stages of sperm development may be associated with changes in sperm DNA methylation, including at genes involved in spermatogenesis and early developmental processes,” Nobles explains.

After fertilisation, the embryo performs a reset: it removes most of the methylation labels brought by the sperm and starts from an almost blank page to establish its own genetic instructions. A small number of genes evade this extensive clearing process, and GNAS is one of them. Its paternal labels remain in place exactly as they were set by the father during the three months in which the sperm cell was formed, and they continue to govern the gene’s activity in the child’s cells.

“Because these genes retain their marks throughout early embryonic development, this raises important questions: do the father’s environmental exposures affect only fertility, or also pregnancy and the child’s health?” Nobles asks. For now, the study does not yet answer that question, and Nobles herself acknowledges that these findings are preliminary. She stresses that further research should be undertaken to reproduce them in other cohorts before any clinical implications are drawn. Yet given the study protocol - a large cohort, long-term follow-up, the timing of sample collection and GNAS’s known role - there are unfortunately good reasons to think another team will reach the same conclusions.