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A meta-analysis-based adverse outcome pathway for the male reproductive toxicity induced by microplastics and nanoplastics in mammals
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This meta-analysis of 39 studies mapped the adverse outcome pathway for microplastic and nanoplastic-induced male reproductive toxicity in mammals. Increased reactive oxygen species triggers a cascade of cellular damage including mitochondrial dysfunction, sperm DNA damage, and disrupted hormone signaling, ultimately leading to reduced sperm quality, impaired spermatogenesis, and decreased testosterone levels.
The male reproductive toxicity of microplastics (MPs) and nanoplastics (NPs) has attracted great attention, but the latent mechanisms remain fragmented. This review performed the adverse outcome pathway (AOP) analysis and meta-analysis in 39 relevant studies, with the AOP analysis to reveal the cause-and-effect relationships of MPs/NPs-induced male reproductive toxicity and the meta-analysis to quantify the toxic effects. In the AOP framework, increased reactive oxygen species (ROS) is the molecular initiating event (MIE), which triggered several key events (KEs) at different levels. At the cellular level, the KEs included oxidative stress, mitochondrial dysfunction, sperm DNA damage, endoplasmic reticulum stress, apoptosis and autophagy of testicular cells, repressed expression of steroidogenic enzymes and steroidogenic acute regulatory protein, disrupted hypothalamic-pituitary-testicular (HPT) axis, and gut microbiota alteration. These KEs further induced the reduction of testosterone, impaired blood-testis barrier (BTB), testicular inflammation, and impaired spermatogenesis at tissue/organ levels. Ultimately, decreased sperm quality or quantity was noted and proved by meta-analysis, which demonstrated that MPs/NPs led to a decrease of 5.99 million/mL in sperm concentration, 14.62% in sperm motility, and 23.56% in sperm viability, while causing an increase of 10.65% in sperm abnormality rate. Overall, this is the first AOP for MPs/NPs-mediated male reproductive toxicity in mammals. The innovative integration of meta-analysis into the AOP analysis increases the rigorism of the results.
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