Polystyrene microplastics disrupt kidney organoid development via oxidative stress and Bcl-2/Bax/caspase pathway

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.