Assessing the impact of perfluoroalkyl substances on liver health: a comprehensive study using multi-donor human liver spheroids.

ABSTRACT:

Background

Although per- and polyfluoroalkyl substances (PFAS) have been linked to chronic liver diseases, the specific cellular and molecular mechanisms by which different PFAS contribute to human liver dysfunction remain unclear. This study aims to elucidate those mechanisms.

Methods

We exposed a multi-donor human liver spheroid model composed of multiple cell types to 20 µM of PFHxS, PFOA, PFOS, or PFNA for seven days, followed by single-cell RNA sequencing and lipid staining.

Results

PFAS impacted liver spheroids in a compound- and sex-specific manner. PFOA and PFHxS increased lipid accumulation, while PFOS and PFNA triggered multiple cancer-related pathways. PFOA upregulated de novo lipogenesis, particularly in female-derived hepatocytes, whereas PFHxS downregula

SUBMITTER: Golden-Mason L 

PROVIDER: S-EPMC12459911 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature