Review article

E-cigarette aerosol constituents modulate Leydig cell steroidogenic pathways: Evidence from experimental models

What we expected vs what we found

Preclinical models consistently show impaired Leydig cell steroidogenesis, yet human studies often report preserved testosterone. This mismatch became the central problem of the paper. Rather than absence of effect, the data suggest early dysfunction that is not captured by circulating hormone measurements.

What is actually being disrupted

Across models, Leydig cells emerge as a vulnerable node. E-cigarette exposure disrupts mitochondrial function, cholesterol transport, and key steroidogenic enzymes. Importantly, this is not limited to nicotine. Nicotine-free aerosols produce similar effects, pointing toward solvents, carbonyls, and metals.

A unifying mechanism

Oxidative stress appears to sit upstream of these changes. It links mitochondrial dysfunction, enzyme suppression, and inflammatory signaling. In some models, this extends further into epigenetic regulation and autophagy, suggesting that steroidogenic failure reflects active cellular adaptation, not just damage.

Why human data look different

Circulating testosterone may remain stable because the HPG axis compensates. This creates a lag between cellular dysfunction and measurable endocrine change. As a result, early effects may be missed unless more sensitive endpoints are used.

Therefore, the biology is consistent. The limitation here is the translation. Resolving this gap will require longitudinal studies with better exposure metrics and repeated endocrine measurements.

Reference

Sailis AB, Mat Noh MA, Leo BF, Faruqu FN, Yee A, Sim MS. E-cigarette aerosol constituents modulate Leydig cell steroidogenic pathways: Evidence from experimental models. Molecular and Cellular Endocrinology. 2026;617:112786. https://doi.org/10.1016/j.mce.2026.112786

Full text available here (until 4 May 2026): link