Exposure to O_3 during pregnancy and offspring asthma induced by OVA: Sensitive window identification

摘要

Background: Evidence proved that gestational ozone (O-3) exposure can increase the risk of neonatal adverse respiratory outcomes, but offspring asthma is unclear.Objective: This study aimed to investigate whether gestational O-3 exposure could exacerbate offspring asthma, and to research the differences in effects of O-3 exposure at different gestational periods on offspring asthma.Methods: The pregnant ICR mice were randomly grouped and were administered O-3 (air as control) at gestational day (GD) 1-6, 7-12, and 13-18, respectively. The pups aged 2-4 weeks were treated with ovalbumin (OVA) to establish a model of early life asthma. Asthma characteristics such as pulmonary inflammation, goblet cell proliferation, airway remodeling, OVA-specific immunoglobulin (Ig) E secretion and cytokines were examined.Results: OVA sensitization and challenge successfully induced asthma in offspring. Compared with the air control, pulmonary inflammation infiltration, mucous secretion, the concentration of OVA-specific IgE, the level of tumor necrosis factor (TNF)-alpha, and T helper (Th) 2-skewed response were significantly exacerbated when O-3 exposure at GD13-18 following inhaling OVA, while pulmonary inflammatory infiltration, mucus secretion, and Th2-skewed response were not significantly changed when O-3 exposure at both GD1-6 and GD7-12. What's more, the above indicators in asthmatic offspring due to O-3 exposure at GD13-18 were more severe than at GD1-6 and GD7-12. Interestingly, the signs of asthma only appeared in the offspring after OVA inhalation. When offspring were not treated with OVA, the prenatal O-3 exposure alone did not lead to asthmatic reactions in offspring. In addition, O-3 exposure at GD13-18 markedly increased the number of neutrophils and macrophages in Bronchoalveolar Lavage Fluid (BALF) of asthmatic offspring, and significantly exacerbated Th2 immune imbalance in asthmatic offspring, but had no effect on Th17 immune imbalance.Conclusion: Exposure to O-3 during pregnancy aggravated asthma in offspring, in which the third trimester is the most sensitive window. (C) 2020 Elsevier Ltd. All rights reserved.