ORIGINAL ABSTRACT

Agricultural work involves exposure to airborne pollutants including dust and pesticides that can cause respiratory effects, yet little is known about these impacts in females. The inflammatory effects of inhaled glyphosate, alone or in combination with common agricultural exposures like lipopolysaccharide (LPS), remain unclear. The objective was to evaluate the inflammatory potential of single and combined exposures to glyphosate and LPS in female mice using physiological and structural measures, and synchrotron imaging. C57BL/6 female mice (n = 20) were intranasally treated with glyphosate (GLY), LPS, LPS + glyphosate (LG), or HBSS (CTL) for 5 days. On day 5, an additional group of mice were transported to the Canadian Light Source synchrotron (CLS) for multiple image x-radiography (MIR) to assess lung injury. Following treatment, mice were euthanized and bronchoalveolar lavage fluid (BAL) and lung tissue were collected. Mice exposed to LG had significantly higher airway restriction; expression of pro-inflammatory cytokines/chemokines TNF-α, KC, IL-6, MCP-1, and MIP-2; levels of myeloperoxidase expression; greater recruitment of cells into the alveolar regions, disruption to the bronchial epithelium in the lungs, and compromised lung air-tissue interfaces in the MIR images compared to other treatment groups. It is likely that inflammatory adaptation is already occurring in the female mice by five days of exposure. These results reveal that female mice exposed to LG displayed physiological, structural, and lung injury effect that were different from mice exposed to LPS and GLY alone.