From environment to organs: individual and combined effects of MPs and PFAS on urinary system health.

As two classes of persistent environmental pollutants, microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) accumulate in the human urogenital system, posing a significant health threat. To elucidate their toxic mechanisms and inform disease prevention, this review systematically examines their individual and combined toxic effects on the urogenital system, with a focus on the kidneys. Evidence indicates that exposure to MPs induces renal injury primarily by triggering oxidative stress, programmed cell death, and disrupting the gut-kidney axis, with toxicity demonstrating size and carrier dependence. As endocrine-disrupting chemicals, PFAS disrupt metabolic and hormonal homeostasis via pathways such as PPAR activation and can induce epigenetic alterations, leading to metabolic disorders, inflammation, and potential carcinogenic risks. Exposure in real environments often occurs as mixtures of pollutants. However, studies on their combined toxicity remain limited and inconsistent. Existing evidence suggests that MPs can act as carriers for PFAS, but their "carrier effect" does not necessarily directly translate to enhanced biological toxicity. Combined exposure may trigger distinct effects including synergistic, additive, or even antagonistic effects through complex mechanisms such as the modulation of bioavailability and the synergistic amplification of cellular stress, with the specific pattern highly dependent on exposure characteristics and the biological system. Overall, research in this field is still in the early stage, and the interaction mechanisms and health risks of combined exposure urgently require systematic elucidation. Future research urgently needs to integrate multidisciplinary approaches from environmental science, toxicology, and epidemiology. Efforts should focus on developing precise internal exposure characterization techniques, dissecting the toxicological mechanisms of interactions in multi-scale models, and conducting systematic population cohort studies. This is essential for advancing the risk assessment paradigm from single-pollutant evaluation to combined-exposure assessment and ultimately formulating effective public health protection strategies.