摘要
Nanoplastics(NPs)have become widespread environmental pollutants with established toxicological impacts on several biological systems.This study investigates the impact of gluconeogenesis disruption in mediating infertility in rats exposed to polystyrene nanoplastics.Adult male rats were randomly assigned to five groups and orally administered NPs at concentrations of 0,100,200,400,or 800μg/kg body weight daily for 55 consecutive days to simulate subchronic exposure.NPs exposure induced excessive reactive oxygen species(ROS),which triggered upregulation of non-coding RNAs(TCONS_00074622 and TCONS_00083977),RNA methyltransferase DNMT2,activated intrinsic apoptosis via BAx,cytochrome c release,and elevated caspase-9 expression,impairing spermatogenesis and reducing sperm quality.Additionally,NPs exposure activated hepatic NF-κB signalling,increased serum pro-inflammatory cytokines(TNF-α,IL-1,IL-6),and caused hepatocellular damage,as demonstrated by increased serum AST and ALT levels.Insulin downregulation and altered expression of key gluconeogenic and glycogen metabolism genes(PCK1,G6PC1,GYS2,GLUT4,and PYGL).Molecular docking and dynamics revealed strong,stable binding of NPs to key metabolic proteins(G6PC1,GLUT4,PCK-1,and PYGL),supporting their involvement in metabolic dysregulation.Taken together,these findings provide significant in vivo and in silico evidence that disruption of hepatic gluconeogenesis serves as a central mediator of NP-induced male infertility.
