Effect of maternal exposure to ozone on reproductive outcome and immune, inflammatory, and allergic responses in the offspring

Abstract

There is growing concern that exposure to air pollutants during pregnancy affects health outcomes in the offspring due to alterations in the development of immune and other homeostatic processes. To assess the risks of maternal inhalation exposure to ozone (O₃), timed pregnant BALB/c mice were exposed to different concentrations of O₃ (0, 0.4, 0.8, and 1.2 ppm) for 4 h/day for 10 days during gestation (GD9–GD18), and pulmonary inflammation and immune responses were assessed in the offspring at 6 weeks-of-age. Maternal O₃ exposure reduced the number of productive dams by 25% at the highest O₃ concentration (1.2 ppm) and decreased the rate of weight gain in the offspring. Delayed-type hypersensitivity responses to bovine serum albumin were suppressed in the female offspring by maternal exposure to the two highest concentrations of O₃, whereas humoral immune responses to sheep red blood cells were not altered in either sex. Maternal exposure to 1.2 ppm O₃ increased lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) of the offspring but did not affect the number of inflammatory cells or levels of total protein, IFN-γ, IL-17, and IL-4 cytokines in BALF, or CD4⁺, CD8⁺, CD25⁺, and TCRβ⁺CD1d⁺ T-cells in the spleen. Offspring born from air-exposed dams sensitized early in life (postnatal day [PND] 3) to ovalbumin (OVA) antigen and then challenged as adults developed eosinophilia, elevated levels of LDH activity and total protein in BALF, and increased pulmonary responsiveness to methacholine, compared with animals sensitized at PND42. Maternal O₃ exposure in the 1.2 ppm O₃ group decreased BALF eosinophilia and serum OVA-specific IgE in the female offspring sensitized early in life but did not affect development of allergic airway inflammation by offspring sensitized late in life. In summary, maternal exposure to O₃ affected reproductive outcome and produced modest decreases in immune function and indicators of allergic lung disease in surviving offspring.

Keywords::

• Ozone
• inhalation
• immunotoxicity
• allergy
• pregnancy
• mice

Acknowledgements

The project was funded by US EPA through the Oak Ridge Universities Association, TN. The authors wish to thank E. Lappi, P. Evansky, W. Zhu, E. Boykin, M. Daniels, S. Cho, G. McGee, J. Richards, J. Lehmann, C. Copeland, W. Williams, and D. Andrew for technical assistance. They appreciate the careful reviews by Drs. Marsha Ward and Janice Dye. This article has been reviewed by the US Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.

Declaration of interest

The authors report no declarations of interest.