More airway smooth muscle in males versus females in a mouse model of asthma: A blessing in disguise?

Abstract

Mouse models are helpful in unveiling the mechanisms underlying sex disparities in asthma. In comparison to their female counterparts, male mice are hyperresponsive to inhaled methacholine, a cardinal feature of asthma that contributes to its symptoms. The physiological details and the structural underpinnings of this hyperresponsiveness in males are currently unknown. Herein, BALB/c mice were exposed intranasally to either saline or house dust mite once daily for 10 consecutive days to induce experimental asthma. Twenty-four hours after the last exposure, respiratory mechanics were measured at baseline and after a single dose of inhaled methacholine that was adjusted to trigger the same degree of bronchoconstriction in both sexes (it was twice as high in females). Bronchoalveolar lavages were then collected, and the lungs were processed for histology. House dust mite increased the number of inflammatory cells in bronchoalveolar lavages to the same extent in both sexes (asthma, P = 0.0005; sex, P = 0.96). The methacholine response was also markedly increased by asthma in both sexes (e.g., P = 0.0002 for asthma on the methacholine-induced bronchoconstriction). However, for a well-matched bronchoconstriction between sexes, the increase in hysteresivity, an indicator of airway narrowing heterogeneity, was attenuated in males for both control and asthmatic mice (sex, P = 0.002). The content of airway smooth muscle was not affected by asthma but was greater in males (asthma, P = 0.31; sex, P < 0.0001). These results provide further insights regarding an important sex disparity in mouse models of asthma. The increased amount of airway smooth muscle in males might contribute functionally to their greater methacholine response and, possibly, to their decreased propensity for airway narrowing heterogeneity.

Recombinant Art v4.01 protein produces immunological tolerance by subcutaneous immunotherapy in a wormwood pollen-driven allergic asthma female mouse model

“…Finally, only female mice were used in this study, and it was not possible to exclude the influence of gender effect on the results of the study. In addition, some studies have shown that airway responsiveness to methacholine was higher in male mice [ 38 , 39 ]. So gender effect should be further investigated in the future studies.…”

A Quick Method to Assess Airway Distensibility in Mice

“…While airway distensibility was greater in females than males in BALB/c mice, an inverse trend was observed in C57BL/6 mice. Interestingly, we have recently demonstrated in BALB/c mice that the thickness of the epithelium and the content of airway smooth muscle were both greater in males than females [ 18 ], perhaps explaining the lower airway distensibility in the former in this mouse strain. A similar study should be conducted to investigate whether these structural features also vary with sex in C57BL/6 mice and whether they are associated with a sexual dimorphism in airway distensibility.…”

“…Mice were anesthetized and put under general analgesia using ketamine (100 mg/kg) and xylazine (10 mg/kg), and then tracheotomized and connected to the flexiVent (FX Module 2, SCIREQ, Montreal, QC, Canada) as previously described [ 17 , 18 ]. They were ventilated mechanically at a tidal volume of 10 mL/kg with an inspiratory-to-expiratory time ratio of 2:3 at a breathing frequency of 150 breaths/min and with a positive end-expiratory pressure of 3 cmH 2 O.…”