Sex-dependent salivary microRNA expression profiles and psychophysiological responses to acute stress in healthy adults

MicroRNAs (miRNAs) have attracted great interest as potential biomarkers in several research domains, including acute and chronic stress conditions. While most of these studies focused on circulating blood miRNA levels, the investigation on the feasibility and utility of miRNAs as biomarkers of stress in other biological fluids, such as saliva, has just started. The objective of the present study was to explore changes in the expression levels of candidate salivary miRNAs following acute stress in a sample (n = 111) of healthy participants, and to examine their potential associations with psychophysiological parameters and biological sex. Participants were exposed to an immersive multimodal environment stress test, i.e. the IMVEST protocol, which induced clear psychophysiological stress responses as evidenced by increased subjective perception of stress, elevated cortisol levels, increased heart rate, and reduced heart rate variability. Among the miRNAs that were reliably detectable in all participants, miR-21, miR-25, miR-26b, miR-29a, and miR-200a showed significant changes in their expression levels after stress exposure. Also, significant sex differences in expression levels and/or stress responses were found for miR-21, miR-23a, miR-26b, and miR-29a. These results suggest that these specific miRNAs may represent promising candidate markers associated with stress-related biological responses. On the other hand, other candidate miRNAs (miR-126, miR-144, and miR-183) showed significant changes after stress exposure and/or between sexes, but were detectable only in some participants, thus questioning their utility as reliable salivary biomarkers.