Abstract：
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.
摘要：
微塑料(MPs)和纳米塑料(NPs)的雄性生殖毒性已引起人们的极大关注,但是潜在的机制仍然支离破碎。本综述对39项相关研究进行了不良结局通路(AOP)分析和荟萃分析。通过AOP分析揭示MPs/NPs诱导的男性生殖毒性的因果关系，并通过荟萃分析量化毒性作用。在AOP框架中,增加的活性氧（ROS）是分子启动事件（MIE），这在不同级别触发了几个关键事件(KE)。在细胞层面,KEs包括氧化应激，线粒体功能障碍，精子DNA损伤,内质网应激,睾丸细胞凋亡和自噬，抑制类固醇生成酶和类固醇生成急性调节蛋白的表达，下丘脑-垂体-睾丸（HPT）轴中断，和肠道微生物群的改变。这些KEs进一步诱导睾酮的减少，受损的血-睾丸屏障（BTB），睾丸炎症,和组织/器官水平的精子生成受损。最终,精子质量或数量下降被注意到并通过荟萃分析证明，这表明MPs/NPs导致精子浓度下降599万/毫升，精子活力14.62%，精子活力为23.56%，同时导致精子异常率增加10.65%。总的来说,这是哺乳动物中第一个针对MPs/NPs介导的雄性生殖毒性的AOP。将荟萃分析创新地整合到AOP分析中增加了结果的严格性。
