Zhang Anxiu, Wang Yujiao, Xue Qunhang, Yao Jiaxin, Chen Long, Feng Shuqi, Shao Juan, Guo Zhongyuan, Zhou Bingrui, Xie Jun
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, 030001, PR China.
School of Forensic Medicine, Shanxi Medical University, 98 University Street, Yuci District, Jinzhong, 030606, Shanxi, PR China.
Chem Biol Interact. 2025 Jul 5;419:111642. doi: 10.1016/j.cbi.2025.111642.
Microplastics (MPs), particularly polystyrene microplastics (PS-MPs), have emerged as significant environmental pollutants with potential risks to human health. Their presence has been detected in human tissues, including blood and placental tissue, raising concerns about developmental effects. However, MPs' effects on the development of human organs are still mostly unknown. The kidney is essential to detoxification and waste excretion in the body and is highly sensitive to toxic substances, making it an important focus for research on toxicity. To study kidney development, human induced pluripotent stem cell (hiPSC)-derived kidney organoids offer a useful in vitro model. This research specifically examines the consequences of PS-MPs on the differentiation of hiPSCs into kidney organoids. Different concentrations of PS-MPs (0, 1.25, 2.5, 5, 10, 20 μg/mL) were set according to the concentration of PS-MPs detected in blood at 1.6 μg/mL. The aim is to understand how environmental contaminants may impact kidney development at the cellular level. Our findings indicate that PS-MP exposure leads to nephron progenitor cell damage and disrupts key processes involved in kidney development, including nephron formation and epithelial cell differentiation. Mechanistically, we demonstrate that PS-MPs induce mitochondrial oxidative stress, activate the Bcl-2 protein family, and trigger apoptosis via the Bcl-2/Bax/caspase-9/caspase-3 signaling pathway. This disruption ultimately impairs normal kidney organoid formation. These results underscore the detrimental impact of PS-MPs on embryonic kidney development and highlight the urgent need for further investigation into the health risks associated with microplastic exposure during early human development.
微塑料（MPs），尤其是聚苯乙烯微塑料（PS-MPs），已成为重要的环境污染物，对人类健康存在潜在风险。在包括血液和胎盘组织在内的人体组织中已检测到它们的存在，这引发了人们对其发育影响的担忧。然而，微塑料对人体器官发育的影响大多仍不为人知。肾脏对于人体的解毒和废物排泄至关重要，并且对有毒物质高度敏感，这使其成为毒性研究的重要焦点。为了研究肾脏发育，人诱导多能干细胞（hiPSC）衍生的肾脏类器官提供了一种有用的体外模型。本研究具体考察了PS-MPs对hiPSCs分化为肾脏类器官的影响。根据在血液中检测到的PS-MPs浓度为1.6μg/mL，设置了不同浓度的PS-MPs（0、1.25、2.5、5、10、20μg/mL）。目的是了解环境污染物如何在细胞水平上影响肾脏发育。我们的研究结果表明，暴露于PS-MPs会导致肾祖细胞损伤，并扰乱肾脏发育过程中涉及的关键过程，包括肾单位形成和上皮细胞分化。从机制上讲，我们证明PS-MPs会诱导线粒体氧化应激，激活Bcl-2蛋白家族，并通过Bcl-2/Bax/caspase-9/caspase-3信号通路触发细胞凋亡。这种破坏最终损害了正常肾脏类器官的形成。这些结果强调了PS-MPs对胚胎肾脏发育的有害影响，并突出了迫切需要进一步调查人类早期发育过程中与微塑料暴露相关的健康风险。
