Prenatal Ozone Exposure Reprograms Offspring Antibodies to Heighten Allergy Risk

Ground-level ozone, the reactive gas best known for choking summer smog over cities, has long been associated with asthma attacks and respiratory inflammation in people who breathe it. But a new study published in Nature Communications suggests that the most consequential damage from ozone exposure may occur before birth, silently rewiring the immune systems of the next generation. A research team led by Xiaoyun Wu, Huifeng Yue, and Nan Sang at Shanxi University, working with collaborators at Shanxi Bethune Hospital and Shanxi Medical University, reports evidence that ozone exposure during mid-to-late pregnancy activates the maternal immune system in a way that alters antibody chemistry in offspring, leaving them—particularly males—more vulnerable to severe allergic reactions.

The investigation began with an epidemiological signal. The researchers conducted a retrospective analysis of 5,299 pregnancies and found that maternal exposure to elevated ozone concentrations during the middle and late stages of gestation was associated with markers of maternal immune activation, including increased risks of neutrophil and monocyte abnormalities. Maternal immune activation, often abbreviated MIA, is a well-documented phenomenon in immunology: when a pregnant mother’s immune system is provoked by infection or inflammatory stimuli, the resulting inflammatory state can shape fetal development in lasting ways. What makes the new work striking is that it links this activation not to a virus or bacterium, but to an environmental pollutant, and traces its consequences all the way down to the sugar decorations on antibodies passed from mother to child.

Epidemiological studies have previously hinted that prenatal oxidative stress—the biochemical wear caused by reactive oxygen species—correlates with heightened allergy susceptibility in children. Correlation, however, is not causation, and the authors of the new study set out to close that gap. Using an animal model in which pregnant dams were exposed to ozone to induce maternal immune activation, the team demonstrated that the offspring of these dams exhibited measurably heightened susceptibility to allergic responses, with male offspring showing the most pronounced effects. This sex bias is notable, because allergic disease epidemiology in humans also shows sex-dependent patterns, and the study offers a mechanistic thread that could help explain why.

The mechanistic heart of the paper lies in glycobiology, the study of the sugar chains attached to proteins. Antibodies of the immunoglobulin G class, or IgG, are not simply protein molecules; they carry N-linked glycans—branched sugar structures attached at specific asparagine residues in the Fc region—that profoundly influence how the antibody behaves. The composition of these glycans determines which Fc receptors the antibody engages on immune cells, and thereby whether an antibody-antigen complex triggers a calm clearance response or a full-blown inflammatory cascade. The researchers found that maternal immune activation disrupts two processes involving IgG: the transfer of maternal IgG across the placenta to the fetus, and the glycosylation machinery that decorates IgG in the neonate.

Specifically, the team identified perturbations in Mgat3-mediated N-acetylglucosamine, or GlcNAc, modifications. Mgat3 encodes an enzyme, N-acetylglucosaminyltransferase III, that adds a bisecting GlcNAc residue to N-glycans—a seemingly small chemical alteration with outsized immunological consequences. In the offspring exposed to maternal immune activation in utero, this glycosylation program was disturbed, and the perturbation preferentially activated IL-17 and TNF signaling in juvenile males. Interleukin-17 and tumor necrosis factor are pro-inflammatory cytokines central to neutrophil-driven inflammation and to several autoimmune and allergic pathologies, so their preferential activation provides a plausible route by which early-life glycan changes translate into inflammatory disease risk.

The story does not end in juvenility. The researchers traced a transcriptional circuit that sustains the altered glycosylation into adulthood. Downstream transcription factors c-Jun and c-Fos—components of the AP-1 complex, a classic node linking inflammatory signaling to gene expression—activate the gene Mgat4a in adulthood, which in turn sustains GlcNAc glycosylation of IgG. In other words, the glycan abnormality imprinted by prenatal ozone exposure is not a transient neonatal phenomenon; it is actively maintained throughout life by a self-perpetuating transcriptional program. This finding elevates the study from a description of a developmental insult to a demonstration of a durable molecular memory of prenatal environment.

The functional consequence of this sustained glycosylation is the most clinically resonant part of the work. The altered GlcNAc glycosylation of IgG was associated with enhanced affinity between IgG and FcγRIII, an activating Fc gamma receptor expressed on immune cells such as macrophages, neutrophils, and natural killer cells. When IgG bound to an allergen engages FcγRIII more avidly, the resulting cellular activation is stronger, and in the context of anaphylaxis—an acute, potentially lethal systemic allergic reaction—the inflammatory response becomes more severe. The offspring in the ozone-exposure model therefore did not merely produce more antibodies or respond to more allergens; their antibodies had been chemically retuned to provoke fiercer inflammatory reactions upon encounter with a trigger.

This chain of evidence—environmental exposure, maternal immune activation, disrupted IgG transfer and glycosylation, sex-biased cytokine signaling, transcriptional maintenance, and enhanced Fc receptor affinity culminating in worse anaphylaxis—represents an unusually complete mechanistic arc for a study bridging environmental science and immunology. The authors describe their work as connecting environmental epidemiology, immunology, and glycobiology, and the description is apt. Few studies have followed a single pollutant exposure from a population-level association in thousands of pregnancies down to a specific enzyme-mediated sugar modification on a specific antibody class, and then shown how that modification changes receptor binding and disease severity in a living animal.

The implications for public health are considerable. Ozone is a secondary pollutant formed when nitrogen oxides and volatile organic compounds react under sunlight, and climate change is expected to intensify ozone episodes in many regions. If the mechanisms identified in this study operate in humans as the epidemiological component suggests, then protecting pregnant people from ozone exposure becomes not merely a respiratory health measure but a developmental one, with the potential to reduce allergic disease burden in the next generation. The finding that male offspring are preferentially affected adds a further layer of nuance for risk assessment, since it suggests that the same exposure may produce sex-differentiated disease vulnerability.

Caveats remain, as they do in any study that combines human association data with animal experimentation. The retrospective epidemiological analysis establishes a link between gestational ozone exposure and maternal immune activation markers, but the causal chain was demonstrated experimentally in mice, and translating glycosylation biology across species will require further validation. Nevertheless, the study opens concrete research avenues: monitoring IgG glycosylation patterns in children born after high-ozone pregnancies, investigating whether Mgat3 and Mgat4a pathways can be therapeutically modulated, and testing whether reducing maternal inflammation during gestation can normalize offspring antibody chemistry. For a field that has long asked why allergic diseases keep rising despite stable genetic backgrounds, the answer emerging from Taiyuan is sobering: part of the risk may be written into the immune system before birth, in the language of sugars, by the air the mother breathes.

Subject of Research: How prenatal ozone exposure activates maternal immunity and alters offspring IgG glycosylation to increase allergy susceptibility

Article Title: Elevated ozone activates maternal immunity to drive offspring IgG-mediated anaphylaxis through IgG glycosylation alterations

Article References: Wu, X., Gong, Z., Tian, Y., Liang, X., Wu, M., Zhu, H., Zhang, J., Hu, Y., Li, B., Li, P., Ji, X., Yue, H., & Sang, N. (2026). Elevated ozone activates maternal immunity to drive offspring IgG-mediated anaphylaxis through IgG glycosylation alterations. Nature Communications. https://doi.org/10.1038/s41467-026-77756-x

Image Credits: AI Generated

DOI: 10.1038/s41467-026-77756-x

Keywords: ozone, air pollution, maternal immune activation, IgG, glycosylation, anaphylaxis, allergy, prenatal exposure, Mgat3, FcγRIII, IL-17, oxidative stress