Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, 030001, China.
Lee Kong Chian School of Medicine, Nanyang Technological University, 639739, Singapore.
Environ Pollut. 2024 Nov 1;360:124645. doi: 10.1016/j.envpol.2024.124645. Epub 2024 Jul 31.
Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 μm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity.
微塑料（MPs）已成为一种普遍存在的环境污染物，引起了全球关注。它们在人胎盘和胎儿器官中的检测引发了人们对 MPs 在早期器官发生期间潜在危害的担忧。肾脏是一个重要的多功能器官，在成年期容易受到 MPs 的损害。然而，由于缺乏合适的模型，MP 暴露对人类肾发生的确切不良影响仍不清楚。在这里，我们利用体外人肾类器官研究 MPs 对早期肾脏发育的潜在影响。在肾祖细胞（NPC）阶段，将聚苯乙烯 MPs（PS-MPs，1μm）施加于人肾类器官，该阶段是早期肾脏发育和模式形成的关键阶段。我们通过对肾类器官的连续检查，描述了 PS-MPs 对肾发生的各个阶段的影响，包括 NPC、肾小囊和逗号形体。在 NPC 阶段观察到 PS-MPs 附着在细胞表面，并在肾类器官中的肾小球样结构内积累。此外，PS-MPs 的短期和长期暴露均导致类器官体积减小和肾单位结构异常。PS-MP 暴露会增加活性氧（ROS）的产生，导致早期肾脏发育中 NPC 凋亡。凋亡增加、细胞活力降低和 NPC 减少可能是 PS-MP 处理下观察到的类器官体积减小的原因。在 NPC 和终点阶段的转录组分析显示，Notch 信号下调，导致近端和远端管状结构受损，从而破坏了 PS-MP 暴露后的正常肾单位模式形成。我们的研究结果强调了 PS-MPs 对人类肾脏发育的显著破坏作用，为 PS-MP 诱导的肾毒性的机制提供了新的见解。
