Air pollution, sperm DNA methylation and male fertility

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

Worldwide, air pollution - indoors and outdoors combined - causes around 7 million premature deaths each year. Those it does not kill may develop numerous conditions, including strokes, heart attacks, high blood pressure, asthma, acute respiratory infections, lung cancer and neurological disorders such as cognitive decline or Alzheimer’s disease. During the 2010s, studies in andrology multiplied, and the medical community came to understand that exposure to exhaust emissions and fine particulate matter also reduces sperm concentration and motility in men.

Until the 2020s, it was known that semen quality was harmed, but not exactly how these environmental assaults could leave an imprint capable of being passed to the embryo. 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 the DNA methylation of sperm, posing a potential threat to reproductive health.

Air pollution and male fertility: a hazardous link

This is one of the largest studies ever conducted on the subject. It tracked more than 2,000 men from Salt Lake City, Utah, over four years, from 2013 to 2017. Each participant provided a semen sample when enrolled, followed by further samples after two, four and six months. This interval reflects the length of spermatogenesis: the roughly three-month cycle in which a stem cell in the testicle divides and becomes a functional sperm cell.

By spacing the samples in this way, researchers obtained a wholly new generation of sperm on each occasion, produced during the weeks since the preceding collection. They could then compare every sample with air-quality records for the corresponding period.

Nitrogen dioxide and ozone in Salt Lake City

The team examined four pollutants commonly found in urban settings: sulphur dioxide, fine particulate matter, nitrogen dioxide and ozone. Salt Lake City has higher concentrations than many other places, caught between heavy traffic and homes heated largely by natural gas. Burning this fuel, along with 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, specifically, they emerged from the analysis as having the greatest influence on sperm DNA methylation.

Methylation is a natural biological mechanism that enables a cell to silence a gene without deleting it. It attaches a methyl group, a small “chemical label”, which prevents the proteins that read a sequence from gaining access to it. The gene is still present, but is no longer expressed. A sperm cell therefore reaches the egg carrying the father’s genetic code, along with a set of labels specifying which of its genes must remain inactive.

A problematic gene

Matching the samples with pollution data identified 39 of these displaced labels. Only one particularly captured the researchers’ attention: the label placed on the GNAS gene (Guanine Nucleotide-binding protein, Alpha Stimulating activity polypeptide), which behaves differently from the overwhelming majority of genes.

Its activity depends directly on which parent passed it on. The copy inherited from the father and that inherited from the mother carry different labels, with one remaining active while the other is inactive. GNAS has also featured in other research connecting semen quality with fetal development, placing it precisely at the meeting point of the study’s two concerns.

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

GNAS methylation and embryo development

Following fertilisation, the embryo clears away most of the methylation labels brought by the sperm cell, starting from an almost blank page as it builds its own genetic instructions. A small number of genes evade this extensive reset, and GNAS is one of them. Its paternal labels remain in place, exactly as the father established them during the three months in which the sperm was produced, and they continue to govern the gene’s activity in the child’s cells.

“Since 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 the findings are preliminary. She stresses that further work must be carried out to reproduce them in other cohorts before any clinical implications are drawn. Yet given the study protocol - its large cohort, lengthy follow-up, sampling schedule and GNAS’s known role - there are unfortunately good reasons to think another team will reach the same conclusions.