Work

Adrenal injury induced by real-ambient PM2.5: Mechanisms of disrupted Shh/Wnt signaling crosstalk

Year: 2025

Type: article

Abstract: Fine particulate matter (PM 2.5 ) exposure is known to induce systemic endocrine disruption, yet the specific mechanisms underlying adrenal injury remain elusive. This study investigates the hypothesis that PM 2.5 impairs adrenal homeostasis by disrupting key paracrine signaling pathways, Sonic hedgehog (Shh) and Wnt/β-catenin, which are vital for adrenal cortical differentiation and function. Utilizing a novel real-ambient exposure system that closely mimics human inhalation exposure, as opposed to traditional instillation models, we assessed the pathological and endocrine-disrupting effects of PM 2.5 on murine adrenal glands. Our results demonstrate that PM 2.5 exposure triggered hypothalamic-pituitary-adrenal (HPA) axis activation and caused significant adrenal structural damage, including cortical architecture disruption and enhanced inflammation. Crucially, we found that these effects were associated with the dysregulation of both Shh and Wnt signaling pathways. The data suggest that PM 2.5 may hinder adrenal self-renewal and repair by impairing these critical pathways. Collectively, our findings indicate that PM 2.5 -induced adrenal dysfunction involves inflammatory responses and the disruption of Shh and Wnt signaling, highlighting their potential key role in preserving adrenal endocrine health.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119497