Larger-sized polystyrene nanoplastics enhance steroid hormone synthesis in mice: Potential role of gut-testis axis

Nanoplastics (NPs) can accumulate in the testis, inducing male reproductive toxicity. However, their effects on steroidogenesis remain controversial, and the underlying mechanisms are not fully elucidated. This study explored the impact of gut microbiota dysbiosis on steroid hormone levels in mice exposed to low-level of polystyrene (PS) NPs of two sizes: 500 nm (PS500) and 100 nm (PS100). The results demonstrated that PS500 enhanced steroid hormone synthesis, with greater increases than PS100. Metabolome analysis confirmed that, in the most significantly enriched pathway of unsaturated fatty acid synthesis, PS500 elevated the levels of arachidonic acid, palmitic acid, oleic acid and stearic acid, while PS100 only increased arachidonic acid and palmitic acid. More importantly, in PS500-exposed group, the gut microbes Desulfovibrio and Allobaculum were linked to unsaturated fatty acid biosynthesis, which was correlated with testicular steroidogenesis; whereas these correlations were absent in PS100-exposed group. It was thus proposed that larger-sized PS500 reduced Desulfovibrio abundance, which may promote oleic acid synthesis, being associated with the enhanced synthesis of steroid hormones in mouse testis. Collectively, these findings shed new light on the role of gut microbiota-metabolism-testis axis in NPs-triggered male reproductive damage, suggesting potential implications for the evaluation and intervention of human health risks from environmental exposure to NPs.