PM2.5 exposure exacerbates cerebral infarction via HPG axis downregulation and pituitary lipid metabolism dysregulation in mice

Epidemiological studies have consistently associated ambient fine particulate matter (PM 2.5 ) with poor post-stroke prognosis. Growing evidence identifies endocrine dysregulation as a critical driver of stroke severity. Nevertheless, the influence of chronic PM 2.5 exposure on the pituitary gland, the core endocrine organ, remains unclear. Male C57BL/6 mice were randomized into 6 groups: filtered air (FA), concentrated PM 2.5 air (CA), FA + sham, CA + sham, FA + distal middle cerebral artery occlusion (dMCAO), and CA + dMCAO. All mice received whole-body inhalation of FA or CA for 12 weeks. After 12 weeks, mice in FA and CA groups were euthanized to collect serum and pituitary. For the other groups, ischemic stroke was induced by dMCAO. Infarct volume was measured at 24 h post-dMCAO, and neurological recovery was assessed at 1, 3, and 7 days post-dMCAO. Chronic PM 2.5 enlarged infarct volume, worsened sensory deficits and delayed motor recovery. It raised fasting glucose, LDL and lowered HDL. Serum LH and testosterone levels were significantly reduced following PM 2.5 exposure, and a positive correlation was observed between LH and testosterone. Multi-omics analysis of the pituitary gland revealed disturbances in lipid metabolism and significant downregulation of Jun expression. Our findings indicate that PM 2.5 exacerbates cerebral infarction, potentially through pituitary lipid metabolic dysfunction and impairment of hypothalamic–pituitary–gonadal (HPG) axis function. The observed downregulation of Jun suggests that Jun may be involved in these pathological processes.