Oral Exposure to Polystyrene Nanoplastics Disrupts Gut–Testis Metabolic Homeostasis and EGR1-Associated Steroidogenic Regulation in Male Mice
Yuqi Wang, Lijun Feng, Jiayi Yuan, Cui Yuan, Ejaz Ali Khan, Kun Qin, Wenbo Chen, Congliang Wang, Liudmila Gerunova, Na Li, Mingzhi Liao, Jinlian HuaAbstract
Polystyrene nanoplastics (PS-NPs) may impair male reproduction through gut–testis metabolic disruption. ICR mice received 100 nm PS-NPs (1 mg/mouse/day) orally for 28 days; fecal microbiota transplantation, metabolomics, sodium butyrate (NaB) supplementation, and TM3-cell assays were used. PS-NPs impaired intestinal barrier integrity and testicular steroidogenesis. Following antibiotic pretreatment, these abnormalities were partially reproduced in exposed-donor recipients relative to control-donor recipients. Untargeted metabolomics showed an FDR-significant decrease in relative testicular butanoic acid levels, while serum butyrate decreased in PS-NP-exposed mice and exposed-donor recipients. In vivo NaB supplementation partially improved reproductive and steroidogenesis-related outcomes in PS-NP-exposed mice. Exploratory analyses and validation experiments implicated a NaB-responsive EGR1–Cyp11a1 regulatory relationship in Leydig cells. These findings suggest that gut-associated butyrate disturbance contributes to PS-NP-induced steroidogenic dysfunction.