a-modified-quechers-hplc-method-for-detection-polycyclic-aromatic

A Modified QuEChERS-HPLC Method for Detection of Polycyclic Aromatic Hydrocarbons in Zebrafish Embryos Exposed to Fine Particulate Matter

Maternal exposure to fine particulate matter (PM2.5), with an aerodynamic diameter of 2.5 &#181;m or less, has been linked to spontaneous abortion and ...

Suzhou Industrial Park Center for Disease Control and Prevention

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 the offspring, but the underlying 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 species (ROS) overproduction, mitochondrial damage, and apoptosis in zebrafish larvae hearts. Blockade of PPARγ through either pharmaceutical inhibition or genetic knockdown only attenuated the changes caused by PFOS, but not those elicited by PFOSA. Conversely, inhibition of AHR alleviated the adverse effects induced by PFOSA but not by PFOS. Both PFOSA and PFOS exhibited similar binding affinities to AHR using molecular docking techniques. The varying ability of PFOS and PFOSA to induce AHR activity in zebrafish embryonic hearts can be attributed to their different capabilities for activating PPARγ. In summary, our findings indicate that PFOS and PFOSA induce excessive ROS production in zebrafish larvae via the PPARγ and AHR pathways, respectively. This oxidative stress in turn causes mitochondrial damage and apoptosis, leading to cardiac defects.

PFOS and PFOSA induce oxidative stress-mediated cardiac defects in zebrafish via PPARγ and AHR pathways, respectively.

An ever-increasing body of research has established a link between maternal PM2.5 exposure and congenital heart diseases in the offspring, but the underlying mechanisms remain elusive. We recently reported that activation of the aryl hydrocarbon receptor (AHR) by PM2.5 causes aberrant mA RNA methylation, leading to cardiac malformations in zebrafish embryos. We hypothesized that PM2.5 can disrupt heart development by inducing mA methylation changes through AHR in mammals. In this study, we observed that extractable organic matters (EOM) from PM significantly impaired cardiomyocyte differentiation in embryonic rat cardiomyoblasts H9c2. Importantly, EOM exposure reduced global mA methylation levels, which was reversed by AHR inhibition. Moreover, AHR, activated by EOM directly promoted the transcription of the demethylase, FTO, leading to global mA hypomethylation. Specifically, AHR-induced FTO overexpression decreased the mA methylation levels of Nox4 mRNA, resulting in NOX4 overexpression and subsequent oxidative stress in EOM samples. We then demonstrated that oxidative stress contributes to the inhibition of cardiomyocyte differentiation by EOM through suppression of Wnt/β-catenin signaling. In summary, our findings indicate that AHR activation by PM directly enhances the expression of the demethylase, FTO, which increases NOX4 expression by reducing its mA methylation. The oxidative stress caused by NOX4 overexpression inhibits Wnt/β-catenin signaling, thereby compromising cardiomyocyte differentiation.

Article	Year
PFOS and PFOSA induce oxidative stress-mediated cardiac defects in zebrafish via PPARγ and AHR pathways, respectively. The Science of the total environment\| PubMed ID: 39181253	2024
Extractable organic matter from PM inhibits cardiomyocyte differentiation via AHR-mediated mA RNA methylation. Journal of hazardous materials\| PubMed ID: 39778483	2025

Yuqin Ma

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