The extensive utilization of plastic products in recent years has resulted in a significant contamination of microplastics (MPs). The ingestion of MPs by aquatic and terrestrial organisms facilitates their transmission to mammals through the food chain. Therefore, the toxicity of MPs has attracted widespread attention from researchers. Previous studies have shown a connection between being exposed to polystyrene MPs (PS-MPs) and issues with male reproductive function. Testosterone, a hormone essential for male reproductive function, is produced and secreted by specialized cells known as Leydig cells, which found in the testicular interstitium. In our prior research, we confirmed that exposure to PS-MPs caused a reduction in testosterone levels by interfering with the LH-mediated LHR/cAMP/PKA/StAR pathway, with LHR being pivotal in this mechanism. However, the molecular mechanism underlying PS-MPs-induced reduction of LHR remains unclear. In this study, mice were respectively given drinking water containing 1000 μg/L PS-MPs characterized by diameters of 0.5 μm, 4 μm, and 10 μm for a period of 180 days. Our findings indicated that exposure to PS-MPs resulted in the proliferation of macrophages as well as their polarization towards the M1 phenotype. Additionally, the presence of PS-MPs triggered the release of tumor necrosis factor alpha (TNF-α) from macrophages, thereby activating nuclear factor-κB (NF-κB) signaling pathway within Leydig cells. The translocation of NF-κB into nucleus facilitated its binding to the promoter region of LHR, which consequently led to the repression of LHR transcription. This transcriptional inhibition resulted in a subsequent suppression of testosterone synthesis and secretion. Overall, this study elucidates a theoretical basis for explaining the interference of PS-MPs on the testosterone synthesis and secretion in Leydig cells from the perspective of the interaction between cells in the testicular interstitium.

中文翻译：

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长期接触聚苯乙烯微塑料可通过 NF-κB 途径诱导 LHR 减少并降低睾酮水平


近年来塑料制品的广泛使用导致了微塑料（MPs）的严重污染。水生和陆生生物摄入 MP 有助于其通过食物链传播给哺乳动物。因此，MPs的毒性引起了研究者的广泛关注。先前的研究表明，接触聚苯乙烯 MP（PS-MP）与男性生殖功能问题之间存在联系。睾酮是男性生殖功能必需的激素，由睾丸间质中的称为间质细胞的特殊细胞产生和分泌。在我们之前的研究中，我们证实接触 PS-MP 会干扰 LH 介导的 LHR/cAMP/PKA/StAR 通路，从而导致睾酮水平降低，而 LHR 在这一机制中至关重要。然而，PS-MPs 诱导 LHR 减少的分子机制仍不清楚。在本研究中，小鼠分别饮用含有1000 μg/L PS-MPs（直径为0.5 μm、4 μm和10 μm）的水，为期180天。我们的研究结果表明，暴露于 PS-MP 会导致巨噬细胞增殖及其向 M1 表型的极化。此外，PS-MP的存在触发巨噬细胞释放肿瘤坏死因子α（TNF-α），从而激活Leydig细胞内的核因子-κB（NF-κB）信号通路。 NF-κB 易位入核促进其与 LHR 启动子区域结合，从而导致 LHR 转录受到抑制。这种转录抑制导致随后睾酮合成和分泌的抑制。 总体而言，本研究从睾丸间质细胞间相互作用的角度阐明了PS-MPs对Leydig细胞睾酮合成和分泌的干扰的理论基础。