Abstract

Voice disorders are an important human health condition. Hydration is a commonly recommended preventive measure for voice disorders though it is unclear how vocal fold dehydration is harmful at the cellular level. Airway surface dehydration can result from exposure to low humidity air. Here we have induced airway surface dehydration in New Zealand White rabbits exposed to a recurring 8-h low humidity environment over 15 days. This model mimics an occupational exposure to a low humidity environment. Exposure to moderate humidity was the control condition. Full thickness soft-tissue samples, including the vocal folds and surrounding laryngeal tissue, were collected for molecular analysis. RT-qPCR demonstrated a significant upregulation of MUC4 (mucin 4) and SCL26A9 (chloride channel) and a large fold-change though statistically non-significant upregulation of SCNNA1 (epithelial sodium channel). Proteomic analysis demonstrated differential regulation of proteins clustering into prospective functional groups of muscle structure and function, oxidative stress response, and protein chaperonin stress response. Together, the data demonstrate that recurring exposure to low humidity is sufficient to induce both transcriptional and translational level changes in laryngeal tissue and suggest that low humidity exposure induces cellular stress at the level of the vocal folds.

Highlights

  • Voice disorders are an important human health condition

  • Acute dehydration by drug-induced diuresis in rabbits was associated with downregulation of various genes related to epithelial development and junctional integrity identified by RNA Sequencing and validated by RTqPCR9,10

  • While this may impact functional studies of the larynx, molecular analysis of vocal folds themselves is facilitated by the absence of a secondary complex structure

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Summary

Introduction

Voice disorders are an important human health condition. Hydration is a commonly recommended preventive measure for voice disorders though it is unclear how vocal fold dehydration is harmful at the cellular level. We have induced airway surface dehydration in New Zealand White rabbits exposed to a recurring 8-h low humidity environment over 15 days. This model mimics an occupational exposure to a low humidity environment. The primary structural difference is that rabbits lack the pair of vestibular folds (“false vocal folds”) present in humans and other animals. While this may impact functional studies of the larynx, molecular analysis of vocal folds themselves is facilitated by the absence of a secondary complex structure. The rabbit is validated as a model for vocal fold ­injury[19,20] and recently as a training model for laryngotracheal ­surgery[21]

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