Irisin and Exercise Ameliorate the Polyethylene Microplastics–Induced Blood–Testis Barrier Disruption via PGC‐1α Activation and AMPK/Nrf2/HO‐1 Signaling

Polyethylene microplastics (PE-MPs), widely used in food packaging, are among the most abundantly produced microplastics; however, their adverse effects on male reproductive health remain poorly understood. Irisin, an exercise-induced adipomyokine, plays a regulatory role in adipogenesis and reproductive function. This study investigated the protective effects of irisin and exercise against PE-MPs-induced reproductive toxicity in male SD rats. Eight-week-old rats were divided into six groups: control, exercise (45 min of swimming/day), irisin (100 ng/kg, sc), PE-MPs (2000 μg/mL), PE-MPs + exercise, and PE-MPs + irisin, and treated for 56 days. End-point assessments included body and reproductive organ weights, sperm parameters, male reproductive hormones, serum irisin with lipid profile, adipogenesis markers, blood-testis barrier proteins, and testicular AMPK/Nrf2/HO-1 signaling. PE-MPs exposure reduced sperm count, motility, and normal morphology, accompanied by increased oxidative stress and reduced antioxidant levels. Serum irisin, testosterone, and FSH levels were markedly decreased but were restored following irisin administration and exercise. Histopathological analysis revealed testicular degeneration, epididymal damage, and adipocyte hypertrophy after PE-MPs exposure, which were ameliorated by both interventions. PE-MPs upregulated adipogenic markers (PPAR-γ and C/EBP-α) and disrupted BTB proteins (occludin and claudin-11); these effects were mitigated via PGC-1α activation and increased irisin expression. PE-MPs exposure decreased Bcl-2 and increased Bax expression, while irisin and exercise restored apoptotic balance. Furthermore, irisin and exercise attenuated PE-MPs-induced NF-κB-mediated inflammation by activating p-αAMPK and Nrf2/HO-1 signaling. In conclusion, irisin and exercise effectively counteract PE-MPs-induced oxidative stress, adipogenesis, and testicular toxicity, highlighting their therapeutic potential in mitigating microplastic-associated male reproductive dysfunction.