Microplastics and nanoplastics: potential implications for testicular inflammation in male mammals

Microplastics and nanoplastics (MNPs) have emerged as widespread environmental contaminants with increasing relevance to human health. Accumulating experimental evidence indicates that the male reproductive system is a potential target of MNPs toxicity, with reported effects on spermatogenesis, steroidogenesis, blood-testis barrier (BTB) integrity, and testicular inflammatory homeostasis. In this review, we summarize current evidence on human exposure, systemic distribution, and the testicular fate of MNPs, and critically evaluate their effects on germ cells, Sertoli cells, Leydig cells, and resident immune cells. Available studies suggest that nanoscale plastic particles can reach the testis under experimental conditions, whereas both micro- and nanoplastics may compromise BTB integrity. Oxidative stress and mitochondrial dysfunction emerge as recurrent upstream events linking MNP exposure to cGAS-STING signaling, inflammatory cell death, impaired steroidogenesis, and macrophage activation. NF-κB and p38 MAPK signaling, M1-like macrophage polarization, and gut microbiota-associated IL-17A responses may further amplify testicular inflammation. However, current mechanistic evidence is derived predominantly from rodent models and oral exposure paradigms, and its relevance to human reproductive health remains incompletely defined. Further studies using diverse mammalian models, environmentally relevant exposures, and cell-resolved particle tracing are needed to clarify the reproductive consequences of MNP exposure.