Towards a Better Understanding of the Human Health Risk of Per- and Polyfluoroalkyl Substances Using Organoid Models

Abstract

The ubiquitous presence of per- and polyfluoroalkyl substances (PFAS) in the environment has garnered global public concern. Epidemiological studies have proved that exposure to PFAS is associated with human health risks. Although evidence demonstrated the toxic mechanisms of PFAS based on animal models and traditional cell cultures, their limitations in inter-species differences and lack of human-relevant microenvironments hinder the understanding of health risks from PFAS exposure. There is an increasing necessity to explore alternative methodologies that can effectively evaluate human health risks. Human organoids derived from stem cells accurately mimic the sophisticated and multicellular structures of native human organs, providing promising models for toxicology research. Advanced organoids combined with innovative technologies are expected to improve understanding of the breadth and depth of PFAS toxicity.

Keywords: PFAS; human health; human organoids; per- and polyfluoroalkyl substances; toxicity assessment.

Figure 1

PFAS exposure routes and organoid models for toxicity assessment. (A) Drinking water and occupational exposure are the main routes of PFAS exposure. PFAS can be transmitted from mother to fetus through the placenta. (B–D) Human organoid models can be applied to evaluate the toxicity of PFAS.

Figure 2

Advances and challenges in human organoid models. (A) Observing human organoids by microscopy is a simple and convenient method for quantitative analysis. (B) Immunofluorescence staining revealed biochemical changes in organoids after exposure to toxicants. (C) Multi-omics sequencing can further explore toxic mechanisms. (D) Microfluidic chips can reduce the heterogeneity of organoid culture and further improve the existing organoid culture methods.