Maternal exposure to NO₂ enhances airway sensitivity to allergens in BALB/c mice through the JAK-STAT6 pathway

Previous studies have indicated that nitrogen dioxide (NO₂) exposure could increase airway sensitivity to allergens for children. Recently, fetal stress was proposed as a crucial factor for allergic airway response occurring in offspring. Considering that there is inadequate evidence linking maternal NO₂ exposure to offspring airway sensitivity to allergens, pregnant Balb/c mice were exposed daily to 2.5 ppm NO₂ throughout the gestation period; then, the offspring were challenged to an allergen (ovalbumin, OVA) to evaluate airway sensitivity. For air + saline group and air + OVA group, offspring mice were maternally exposed to clean air followed by treatment with saline and OVA, respectively, in adulthood. For NO₂ + saline group and NO₂ + OVA group, offspring mice were maternally exposed to NO₂ followed by treatment with saline and OVA, respectively, in adulthood. The results showed that maternal NO₂ exposure increased the level of OVA-immunoglobulin (Ig) E in serum and caused airway hyper-responsiveness and pathological changes in offspring. Furthermore, maternal NO₂ exposure altered the expression of pro-inflammatory factors and impaired the T helper (Th) 1/Th2 balance. In addition, janus kinase)-signal transducer and activator of transcription 6 pathway participated in OVA-induced airway sensitivity of offspring. Our study showed that the potential risk of airway sensitivity to allergens in offspring is enhanced by maternal NO₂ exposure and proposed a possible mechanism for preventing, alleviating, and evaluating the outcomes in polluted environments.