From Exposure to Inheritance: Persistent Microplastic‐Induced Neural and Mitochondrial Dysfunction in Subsequent Generations of <scp> <i>Drosophila melanogaster</i> </scp>

Microplastic contamination poses a critical intergenerational threat to ecosystems and human health, with pervasive infiltration into food chains. This study investigates the developmental and intergenerational consequences of polystyrene microplastic (1.0 μm) exposure (0-25 ppm) in Drosophila melanogaster, evaluating both directly exposed F0 flies and their unexposed F1 offspring. Developmental exposure in F0 adults caused concentration-dependent lifespan shortening (≥ 0.1 ppm) and neurobehavioral impairments (≥ 10 ppm), characterized by reduced locomotion, exploratory deficits, and stress tolerance, with microplastic accumulation detected in heads at ≥ 0.1 ppm. Molecular analyses of F0 heads revealed disrupted acetylcholine metabolism, including elevated acetylcholine (AChE) activity at ≥ 1 ppm, and altered mitochondrial dynamics, characterized by activation of the intrinsic apoptotic pathway, with elevated drICE and Dcp-1 levels, alongside suppression of fusion protein Mfn-2 and ATP5A1. In addition, exposure also reduced F0 adult emergence rates at ≥ 1 ppm. To evaluate indirect intergenerational effects, unexposed F1 offspring were assessed. F1 displayed lifespan reduction at ≥ 10 ppm with persistent locomotor and exploratory deficits at ≥ 1 ppm, though stress tolerance remained unaffected. Notably, no microplastics were detected in F1, yet mitochondrial dysregulation was observed starting at ≥ 1 ppm, with elevated AChE activity. At this concentration, mitochondrial dysregulation persisted: Dcp-1 and Mfn-2 levels were altered at ≥ 1 ppm, and ATP5A1 was suppressed at ≥ 10 ppm, while drICE remained unchanged. No significant changes were observed in F2 adult emergence. Developmental microplastic exposure induces mitochondrial and cellular stress, driving neurobehavioral impairments and lifespan reduction in Drosophila melanogaster, with parental effects persisting in unexposed offspring.