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

Document Type

Review

Publication Date

6-1-2026

Abstract

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.

Keywords

e-cigarettes, HPG axis, microRNAs, steroidogenesis, testosterone

Publication Title

Environmental Toxicology and Pharmacology

ISSN

1382-6689

DOI

10.1016/j.etap.2026.104994

Volume

124

Publisher

Elsevier

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