Acrolein, a major constituent of combustion emissions, induces sexually dimorphic neuroendocrine and metabolic dysfunction
On this page:
Anthropogenic and wildfire smoke emissions are the most prominent contributors to present-day air pollution. Acrolein, a major constituent of these emissions, is on EPA’s priority list of hazardous air pollutants. It is known to cause airway irritancy and inflammation; however, neuroendocrine and systemic health effects are not well characterized. Moreover, few studies have addressed potential sexually dimorphic responses to inhaled stressors. Here, 12-week-old male and female Wistar-Kyoto rats underwent acrolein nose-only inhalation in incremental concentrations (0, 0.1, 0.316, 1ppm) for 30 min (for assessment of ventilatory changes), followed by a 3.5hr exposure at 3.16ppm (n=8/group). We assessed nasal and pulmonary lavages (NALF and BALF), circulating pituitary, adrenal, thyroid and gonadal hormones, and other hallmarks of peripheral stress. We further analyzed circulating biomolecules through serum metabolomics. Acrolein induced potent nasal but not pulmonary injury and vascular leakage (increased NALF total protein, albumin, and LDH activity) in both males and females. However, the inflammatory response was apparent in both nasal and pulmonary airways but only in males. Acrolein caused robust corticosterone release only in males, also displaying glucocorticoid-like effects of lymphopenia and hyperglycemia. Other hormones, such as thyroid-stimulating hormone, triiodothyronine, prolactin, and testosterone, were depleted in acrolein-exposed males. Metabolomic analysis revealed increased lipolysis, muscle protein catabolism, and shifts in mitochondrial respiration markers associated with changes in steroid metabolism in males but not in females. In conclusion, acrolein exposure induces neuroendocrine stress reactions that are linked to changes in circulating metabolites reflective of alterations in metabolic processes within liver, adipose, and muscle tissue. Moreover, these changes are sex-specific, where males show increased susceptibility to systemic stress. This prompts further investigations into neuroendocrine and sex-specific mechanisms that govern peripheral stress from exposure to reactive air pollutants (Does not reflect US EPA policy).