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Pulmonary Exposure to Particles during Pregnancy Causes Increased Neonatal Asthma Susceptibility

¹ Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health; and ² Lung Biology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Alexey V. Fedulov, M.D., Ph.D., Harvard School of Public Health, Dept. of Environmental Health, Molecular and Integrative Physiological Sciences Program, 665 Huntington Ave, HSPH-12, Room 1313, Boston, MA 02115. E-mail: afedulov{at}hsph.harvard.edu

Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control "inert" titanium dioxide (TiO₂) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to "inert" TiO₂. In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO₂ and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO₂. Neonates of mothers exposed to TiO₂ (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both "inert" TiO₂ and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

Key Words: maternal asthma • environmental particles • titanuim dioxide • diesel exhaust particles • susceptibility

CLINICAL RELEVANCE A novel model allowing analysis of environmental exposures in pregnancy on offspring susceptibility to allergy identifies titanium dioxide particles as pro-inflammatory in pregnancy and pro-allergic for neonates.

 

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