PFOS and PFOSA induce cardiac defects in zebrafish via PPARγ and AHR pathways

• 1、School of Public health, Suzhou medical college of Soochow University, Suzhou 215127

Abstract：Perfluorooctane sulfonate (PFOS) and its precursor, perfluorooctane sulfonamide (PFOSA), are widespread in the environment. Evidence suggests a strong link between maternal exposure to PFOS/PFOSA and congenital heart diseases in offspring, but the mechanisms remain unclear. We hypothesized that PFOS and PFOSA induce cardiac defects through the peroxisome proliferator-activated receptor gamma (PPARγ) and aryl hydrocarbon receptor (AHR) pathways, respectively. In this study, we demonstrated that exposing zebrafish embryos to either PFOSA or PFOS caused cardiac malformations and dysfunction. Both PFOS and PFOSA induced reactive oxygen speciesPFOS and PFOSA induce cardiac defects in zebrafish via PPARγ and AHR pathways (ROS) overproduction, mitochondrial damage, and apoptosis in zePFOS and PFOSA induce cardiac defects in zebrafish via PPARγ and AHR pathways, respectively#brafish embryonic hearts. Blockade of PPARγ through pharmaceutical inhibitor or genetic knockdown only attenuated the changes caused by PFOS, not by PFOSA. Conversely, inhibition of AHR alleviated the adverse effects induced by PFOSA but not by PFOS. In summary, our findings indicate that PFOS and PFOSA induce excessive ROS production via the PPARγ and AHR pathways, respectively. This oxidative stress leads to mitochondrial damage and apoptosis, resulting in cardiac defects.?????

Keywords： PFOSA PFOS AHR PPARγ cardiac defects