Polystyrene Nanoparticles Cause Sex-Specific Toxicity in Male Zebrafish, Which Can Be Mitigated by Melatonin

The environmental ubiquity of microplastics raises growing concerns over their reproductive toxicity, although the underlying molecular mechanisms remain unclear. In this study, adult zebrafish were exposed to polystyrene nanoparticles (PSNPs; 0, 0.1, and 1 mg/L) for 14 days, with or without co-treatment of melatonin (1 μM). Exposure to 1 mg/L PSNPs significantly reduced gonadosomatic and brain somatic indices, accompanied by histopathological evidence of structural damage to gonadal tissues. Moreover, PSNPs disrupted hypothalamic-pituitary-gonadal (HPG) axis gene transcription and altered sex hormone levels. PSNPs also induced oxidative stress and apoptosis in gonadal and brain tissues. Notably, these effects were sex-dependent and were largely ameliorated by melatonin co-treatment. Importantly, PSNPs showed differential reproductive toxicity between males and females. These findings highlight the potential of melatonin to mitigate PSNP-induced reproductive toxicity by protecting against oxidative damage and HPG axis disruption while also revealing sex-specific responses to nanoparticle exposure.