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Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-β-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage. • Nanoplastics induced reproductive damage in male mice. • Nanoplastics triggered spermatogenic cell senescence. • Sirt1/ROS axis was involved in the nanoplastic induced spermatogenic cell senescence. • Pterostilbene intervention may be a promising strategy to alleviate nanoplastic damage. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (B[a]P), a representative of polycyclic aromatic hydrocarbons (PAHs), is ubiquitously spread in the environment and showing deleterious impacts on male steroidogenesis, including testosterone synthesis disorder. However, the precise mechanisms involved in B[a]P-induced steroidogenesis perturbation remains obscure. In the present study, we integrated in vivo tests, transcriptome profiling, in vitro assays, and conjoint in silico toxicological approaches to delineate the detailed mechanisms. In mouse models, we observed that B[a]P administration remarkably inhibited testosterone synthesis accompanied by ultrastructural impairments of mitochondria and mitophagosome formation in mouse Leydig cells. Transcriptome profiling showed that B[a]P down-regulated the expression of Ndufa9 , Ndufa6 , Ndufa10 , and Ndufa5 in mouse testes, which are identified as critical genes involved in the assembly and functionality of mitochondrial complex I. In the in vitro tests, the bioactive B[a]P metabolite BPDE induced perturbation of testosterone synthesis by NDUFA10-mediated mitochondrial impairment, which was further exacerbated by mitophagy in TM3 Leydig cells. The findings of in silico toxicological analyses were highly consistent with the experimental observations and further unveiled that B[a]P/BPDE-involved PPARα activation could serve as a molecular initiating event to trigger the decline in Ndufa10 expression and testosterone synthesis. Overall, we have shown the first evidence that mitochondrial compromise in Leydig cells is the extremely crucial target in B[a]P-induced steroidogenesis perturbation. [Display omitted] • B[a]P-induced mitochondrial damage inhibits testosterone synthesis in Leydig cells. • Mitophagy exacerbates B[a]P-induced mitochondrial damage and decline in testosterone. • NDUFA10 participates in B[a]P-mediated impairment of complex Ⅰ and steroidogenesis. • B[a]P-activated PPARα triggers declines in NDUFA10 expression and steroidogenesis. [ABSTRACT FROM AUTHOR]

Sertoli cells play a pivotal role in the complex spermatogenesis process. This study aimed to investigate the effects of PM 2.5 on Sertoli cells using the TM4 cell line and a real time whole-body PM 2.5 exposure mouse model, and further explore the underlying mechanisms through the application of metabolomics and transcriptomics. The results in vivo and in vitro showed that PM 2.5 reduced Sertoli cells number in seminiferous tubules and inhibited cell proliferation. PM 2.5 exposure also induced Sertoli cell dysfunction by increasing androgen binding protein (ABP) concentration, reducing the blood-testis barrier (BTB)-related protein expression, and decreasing glycolysis capacity and lactate production. The results of transcriptomics, metabolomics, and integrative analysis of multi-omics in the TM4 Sertoli cells revealed the activation of xenobiotic metabolism, and the disturbance of glutathione and purine metabolism after PM 2.5 exposure. Further tests verified the reduced GSH/GSSG ratio and the elevation of xanthine oxidase (XO) activity in the PM 2.5 -exposed TM4 cells, indicating that excessive reactive oxygen species (ROS) was generated via metabolic disorder caused by PM 2.5. Moreover, the redox imbalance was proved by the increase in the mitochondrial ROS level, superoxide dismutase (SOD) and catalase (CAT) activity, as well as the activation of the Nrf2 antioxidative pathway. Further study found that the redox imbalance caused by PM 2.5 induced DNA damage response and cell cycle arrest. Additionally, PM 2.5 induced ferroptosis through iron overload and lipid peroxidation. Taken all together, our study provided new insights for understanding proliferation inhibition and dysfunction of TM4 Sertoli cells exposed to PM 2.5 via metabolic disorder and redox imbalance-mediated DNA damage response and ferroptosis. [Display omitted] • PM 2.5 exposure induces Sertoli cell proliferation inhibition and dysfunction. • PM 2.5 disturbs glutathione, purine, and xenobiotic metabolism in TM4 cells. • PM 2.5 induces redox imbalance and causes ferroptosis and DNA damage response in TM4 cells. [ABSTRACT FROM AUTHOR]

In China, studies on lead exposure to grownup are scarce compared to children, although relevant disease burdens for adults are much severe than that in developed countries. The present study evaluated blood lead levels (BLLs) in Chinese adults by data mining using Monte Carlo simulation. A total of 115 scientific studies published between January 1980 and March 2021 reflecting 45,514 Chinese adults were included in the study. After a continuous increase in Chinese adult BLLs from 1980–1983 (GM 74.84 μg/L) to 1994–1996 (GM 92.27 μg/L), BLLs began to decline from 2000–-2002 (GM 80.32 μg/L) to 2016–2018 (GM 21.57 μg/L). This decline implied that the lead phase-out policy in gasoline was effective over the past two decades. The study indicated that North, South, and Southwest China were still relatively high compared to other regions in the past decade. Statistical analysis showed that BLLs of males (GM 68.45 μg/L) were higher than females (GM 56.51 μg/L), smokers (GM 80.96 μg/L) higher than nonsmokers (GM 58.95 μg/L), and populations over 40 (GM 40.43 μg/L) higher than younger populations (GM 40.37 μg/L). The significantly positive correlation between the concentrations of PM2.5 and topsoil lead and BLLs in Chinese adults indicated that air and soil pollution affect adult BLLs. Taken together, our results showed that strict lead control strategies and regular bio-monitoring are needed to maintain low BLLs in the population. [Display omitted] • Blood lead levels of Chinese adults declined since 2002, as determined by Monte Carlo simulation. • Adult blood lead levels were still high in Southwest, North, and South China compared to the rest of China. • Blood lead levels were higher in men, smokers, and people 40 years of age and older. • The concentration of PM2.5 in ambient air had the strongest association with adult blood lead levels. [ABSTRACT FROM AUTHOR]