Assessing Sex‐Specific Effects of Ozone Exposure on Pulmonary Function and Lung Mechanics

Abstract

BackgroundExposure to ground‐level ozone, an oxidative pollutant, causes lung inflammation, which can lead to pulmonary injury and impair lung innate immunity. There is emerging evidence that pulmonary diseases such as asthma affect women disproportionally with a greater degree of severity than men. In addition, most hospitalizations for asthma in women occur during the luteal phase or around the peri‐menstrual stage. However, the combined effect of ozone and sex hormones in respiratory mechanics is unclear. Here, we hypothesized that circulating estrogen levels can regulate pulmonary function and lung mechanics following ozone exposure.MethodsWe performed gonadectomy and hormone replacement (17β‐estradiol, 2 weeks) in a group of adult male and female C57BL/6 mice. In control females, the stages of the estrous cycle were monitored by daily by vaginal smear, and confirmed by serum sex hormone levels. We exposed animals to 1 ppm of ozone or filtered air (FA) for 3 hours, and we compared lung function 24h after exposure with a methacholine challenge (MCh; 0 – 50 mg/ml) using the FlexiVent system.ResultsWe observed significant changes in respiratory parameters (Ers, H, Rrs, RN, G) in males and females, and in females exposed to ozone at different stages of the estrous cycle, at the two highest MCh concentrations. The pressure‐volume curves obtained demonstrated similar MCh concentration‐dependent changes. Gonadectomized males exposed to ozone had higher Rrs and Ers than females and males exposed to FA, and treatment with estradiol ameliorated these effects. Surprisingly, female mice in the metestrus and diestrus stages exposed to FA had higher Rrs and Ers values than when compared to the proestrus and estrus stages. Contrarily, exposure to ozone caused a decrease in parameters (Ers, Rrs) during metestrus and diestrus stages, but a slight increase of these in the proestrus and estrus stages.ConclusionsOur results indicate that pulmonary function following ozone exposure can be affected by circulating hormone levels. Future studies examining diseases associated with environmental pollutants should consider the women's menstrual cycle.Support or Funding InformationThe authors thank the Pennsylvania State University College of Medicine Genome Sciences Core Facility for Bioanalyzer analysis. The authors also thank Todd Umstead and Susan Di Angelo for assistance with training and experiments, and Dr. Joanna Floros for the ozone equipment. NIH Grant K01HL133520.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.