PM2.5 induces cardiac malformations via PI3K/akt2/mTORC1 signaling pathway in zebrafish larvae

An Overview of Adverse Outcome Pathway Links between PM2.5 Exposure and Cardiac Developmental Toxicity

“…Common cardiac malformations included pericardial edema, balloon-shaped heart chambers, liner heart, string heartbeat, bradycardia, gradual increase in string heart distance and pericardial area, etc. 8,[18][19][20][21][22][23]42,43,83 Similarly, PM 2.5 exposure resulted in pericardial edema and decreased heart rate in zebrafish embryos. 84 Furthermore, exposure to PM 2.5 via air cell injection resulted in elevated heart rate and thickened right ventricular wall thickness in fertile chicken eggs.…”

“…Exposure of zebrafish embryos to EOM resulted in notable changes in cardiac development, including a prominent decrease in heart rate, an elevated incidence of cardiac malformations, and alterations in genes associated with cardiac development (NKX2.5, sox9b, Axin2). Common cardiac malformations included pericardial edema, balloon-shaped heart chambers, liner heart, string heartbeat, bradycardia, gradual increase in string heart distance and pericardial area, etc. ,− ,,, Similarly, PM 2.5 exposure resulted in pericardial edema and decreased heart rate in zebrafish embryos . Furthermore, exposure to PM 2.5 via air cell injection resulted in elevated heart rate and thickened right ventricular wall thickness in fertile chicken eggs .…”

“…Numerous studies documented ROS overproduction induced by PM 2.5 exposure (Table S1). After exposure to extractable organic matter (EOM) from PM 2.5 , ROS levels were found to be observably higher in the hearts of zebrafish embryos than those in the controls. ,− Meanwhile, excessive ROS production was verified in human embryonic stem cells (hESCs) and SD rat whole embryos exposed to PM 2.5 . , Current reports hinted that excessive ROS production could be involved in cardiac malformation by triggering subsequent oxidative stress, ER stress, DNA damage, inflammation, etc.…”

“…Current pieces of the literature confirmed that PM 2.5 induced apoptosis in cardiomyocytes (Table S7). When zebrafish embryos were exposed to EOM, cardiac developmental defects were observed along with a significant increase in the degree of acridine orange staining, the levels of apoptotic markers (caspase-3 and caspase-9) and pro-apoptotic genes (p53 and bax). ,− Maternal exposure to PM 2.5 during pregnancy elevated myocardial apoptosis in offspring rats. , After exposure to PM 2.5 , enhanced apoptosis was observed in the heart of SD rat whole embryos . In most of the available data, myocardial apoptosis was identified to be the essential part of PM 2.5 -caused cardiac development failure, directly responsible for the aberrant formation of the cardiac structure.…”

“…A few studies verified PM 2.5 -induced inhibition of the Wnt/β-catenin pathway (Table S8). It was reported that the Wnt/β-catenin pathway was inhibited in zebrafish embryos exposed to PM 2.5 or EOM. − ,− Current literature has suggested that the Wnt/β-catenin pathway is critical to the differentiation process of cardiomyocytes during cardiac development.…”