Wang Caihong, Ji Xiang, Wang Xiaoya, Song Yunmeng, Pan Chunqiang, Qian Mingrong, Jin Yuanxiang
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China.
Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou, 310015, China.
Environ Pollut. 2025 May 1;372:126014. doi: 10.1016/j.envpol.2025.126014. Epub 2025 Mar 6.
With the extensive use of plastic products, significant amounts of microplastics, nanoplastic particles (NPs), and plasticizers such as Di(2-ethylhexyl) phthalate (DEHP) are continuously released into the environment. However, the toxic effects of NPs alone or in combination with DEHP on mammary glands remain unreported. This study investigates the impacts of NPs and DEHP on the structure and function of mouse mammary epithelial cells and elucidates the underlying molecular mechanisms. We found that co-exposure to NPs and DEHP induced severe pyroptosis, inflammation and oxidative stress in HC11 cells. Co-exposure also caused mitochondrial damage, as evidenced by changes in mitochondrial membrane potential, increase in mitochondrial ROS and inhibition of ATP production. Moreover, NPs and DEHP co-exposure increased the transcriptional levels of endoplasmic reticulum (ER) stress-related genes, activated the inflammation-related NLRP3 signaling pathway, and damaged the cell membrane integrity. Notably, Co-exposure enhanced the ER-mitochondria crosstalk in HC11 cells, as evidenced by the upregulated transcriptional levels of ER Ca channel proteins (Ip3r1, Grp75 and Vdac1), increased mitochondrial Ca levels, and expanded mitochondrial-ER contact areas. In summary, this study revealed that NPs and DEHP co-exposure had the potential to induce pyroptosis and inflammation by enhancing the ER-mitochondria crosstalk, ultimately resulting in injury to mammary glands. These findings would provide some new insights into the molecular mechanisms underlying the toxic effects of NPs and DEHP to mammary glands.
随着塑料制品的广泛使用，大量的微塑料、纳米塑料颗粒（NPs）以及邻苯二甲酸二（2-乙基己基）酯（DEHP）等增塑剂不断释放到环境中。然而，NPs单独或与DEHP联合对乳腺的毒性作用尚未见报道。本研究调查了NPs和DEHP对小鼠乳腺上皮细胞结构和功能的影响，并阐明其潜在的分子机制。我们发现，NPs与DEHP共同暴露可诱导HC11细胞发生严重的焦亡、炎症和氧化应激。共同暴露还导致线粒体损伤，表现为线粒体膜电位改变、线粒体活性氧增加以及ATP生成受到抑制。此外，NPs与DEHP共同暴露增加了内质网（ER）应激相关基因的转录水平，激活了炎症相关的NLRP3信号通路，并破坏了细胞膜完整性。值得注意的是，共同暴露增强了HC11细胞中的内质网-线粒体相互作用，表现为内质网钙通道蛋白（Ip3r1、Grp75和Vdac1）转录水平上调、线粒体钙水平增加以及线粒体-内质网接触面积扩大。总之，本研究表明，NPs与DEHP共同暴露有可能通过增强内质网-线粒体相互作用诱导焦亡和炎症，最终导致乳腺损伤。这些发现将为NPs和DEHP对乳腺毒性作用的分子机制提供一些新的见解。
