1. Academic Validation
  2. AHR-mediated ROS production contributes to the cardiac developmental toxicity of PM2.5 in zebrafish embryos

AHR-mediated ROS production contributes to the cardiac developmental toxicity of PM2.5 in zebrafish embryos

  • Sci Total Environ. 2020 Jun 1;719:135097. doi: 10.1016/j.scitotenv.2019.135097.
Fei Ren 1 Cheng Ji 2 Yujie Huang 1 Stanley Aniagu 3 Yan Jiang 4 Tao Chen 5
Affiliations

Affiliations

  • 1 Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.
  • 2 Medical College of Soochow University, Suzhou, China.
  • 3 Toxicology, Risk Assessment and Research Division, Texas Commission on Environmental Quality, 12015 Park 35 Cir, Austin, TX, USA.
  • 4 Medical College of Soochow University, Suzhou, China. Electronic address: yjiang@suda.edu.cn.
  • 5 Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China. Electronic address: tchen@suda.edu.cn.
Abstract

Recent studies have shown an association between maternal exposure to ambient fine particle matter (PM2.5) and congenital heart defects in the offspring, but the underlying molecular mechanisms are yet to be elucidated. Previously, we demonstrated that extractable organic matter (EOM) from PM2.5 induced heart defects in zebrafish embryos by activating the aromatic hydrocarbon receptor (AHR). Hence, we hypothesized that AHR mediates excessive Reactive Oxygen Species (ROS) production, leading to the cardiac developmental toxicity of PM2.5. To test our hypothesis, we examined AHR activity and ROS levels in the heart of zebrafish embryos under a fluorescence microscope. mRNA expression levels were then quantified using qPCR whereas DNA damage and Apoptosis were detected by immunofluorescence. Our results showed that the AHR inhibitor, CH223191 (CH) as well as the ROS scavenger, N-Acetyl-L-cysteine (NAC), significantly mitigated the PM2.5-induced cardiac malformations in zebrafish embryos. Furthermore, both CH and NAC diminished the EOM-elevated ROS generation, DNA damage and Apoptosis in the test system. Incidentally, both CH and NAC attenuated the EOM-induced changes in the mRNA expression of genes involved in cardiac development (nkx2.5, sox9b), oxidative stress (nrf2a, nrf2b, gstp1, gstp2, sod2, ho1, cat) and Apoptosis (p53, Bax). We further confirmed that AHR activity is a necessary condition for EOM-induced ROS generation, DNA damage and Apoptosis, through AHR knockdown. However, the ROS scavenger NAC did not counteract the EOM-induced AHR activity. In conclusion, our findings suggest that AHR mediates EOM-induced oxidative stress, resulting in DNA damage and Apoptosis, thereby contributing to the cardiac developmental toxicity of PM2.5.

Keywords

AHR; Apoptosis; Heart development; PM2.5; ROS; Zebrafish.

Figures
Products