Mitochondrial perspectives on environmental pollutant-induced male reproductive toxicity

With rapid industrialization and urbanization, environmental pollutants have emerged as a major threat to male reproductive health, and declining semen quality and rising rates of male infertility have now become a global public health concern. Owing to its high energetic demand and specialized cellular organization, the testis is especially vulnerable to pollutants, with mitochondria serving as a principal target because they coordinate energy metabolism and apoptotic control. Here we synthesize evidence on how heavy metals, air pollutants, organic pollutants, endocrine-disrupting chemicals, micro(nano)plastics, pesticides, and mycotoxins injure testicular mitochondria and the mechanisms involved. Current evidence indicates that these pollutants compromise spermatogenesis and androgen production via convergent mitochondrial pathways, including oxidative stress, metabolic disruption, mitochondria-dependent apoptosis, imbalance of mitochondrial dynamics, suppressed biogenesis, and dysregulated mitophagy. Importantly, these mechanisms are not independent, since individual pathways may dominate under specific exposure scenarios, yet they can also intersect and mutually reinforce one another to generate a multistep cascading network that culminates in reproductive injury. Therefore, mitochondrial dysfunction represents a central convergent node through which pollutants drive male reproductive toxicity. Future work should prioritize low-dose, long-term, and mixture exposure models, integrate multi-omics approaches with testicular organoid platforms, define key regulatory pathways, identify early biomarkers, and evaluate mitochondria-targeted interventions to support environmental risk assessment and prevention of male reproductive injury.