MicroRNA-mediated disruption of testosterone signaling associated with e-cigarette exposure

Electronic cigarette (e-cigarette) use is increasing worldwide, yet its effects on male endocrine and reproductive health remain poorly defined. Beyond nicotine, e-cigarette aerosols contain aldehydes, metals, and particulate matter capable of perturbing pathways essential for steroidogenesis. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of hypothalamic-pituitary-gonadal axis signaling and Leydig cell function, and multiple miRNAs involved in GnRH release, gonadotropin synthesis, and testosterone biosynthesis are responsive to oxidative and metabolic stressors present in e-cigarette aerosols. Although direct evidence in e-cigarette users is limited, findings from studies of nicotine, flavoring agents, and metal exposures support the plausibility that e-cigarettes may alter miRNA expression and impair steroidogenic processes. This hypothesis-generating review synthesizes current evidence linking miRNA dysregulation to testosterone biosynthesis, proposes candidate e-cigarette constituents capable of modulating these miRNAs, and highlights critical gaps requiring experimental validation. Overall, miRNAs may represent integrative mediators and potential biomarkers of e-cigarette-associated testicular toxicity.