Jason T. Magnuson | Search USGS

USGS2021

miR133b microinjection during early development targets transcripts of sardiomyocyte ion channels and induces oil-like cardiotoxicity in zebrafish (Danio rerio) embryos

Previous studies have shown that altered expression of a family of small noncoding RNAs (microRNAs, or miRs) regulates the expression of downstream mRNAs and is associated with diseases and developmental disorders. miR133b is highly expressed in mammalian cardiac and skeletal muscle, and aberrant expression is associated with cardiac disorders and electrophysiological changes in cardiomyocytes. Similarly, cardiac dysfunction has been observed in early life-stage mahi-mahi ( Coryphaena hippurus ) exposed to crude oil, a phenotype that has been associated with an upregulation of miR133b as well as subsequent downregulation of a delayed rectifier potassium channel (I Kr ) and calcium signaling genes that are important for proper heart development during embryogenesis. To examine the potential role of miR133b in oil-induced early life-stage cardiotoxicity in fish, cleavage-stage zebrafish ( Danio rerio ) embryos were either (1) microinjected with ∼3 nL of negative control miR (75 μM) or miR133b (75 μM) or (2) exposed to a treatment solution containing 5 μM benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, as a positive control. At 72 h post fertilization (hpf), miR133b-injected fish exhibited BaP-like cardiovascular malformations, including a significantly increased pericardial area relative to negative control miR-injected embryos, as well as a significantly reduced eye area. qPCR revealed that miR133b microinjection decreased the abundance of cardiac-specific I Kr kcnh6 at 5 hpf, which may contribute to action potential elongation in oil-exposed cardiomyocytes. Additionally, ryanodine receptor 2, a crucial calcium receptor in the sarcoplasmic reticulum, was also downregulated by miR133b. These results indicate that an oil-induced increase in miR133b may contribute to cardiac abnormalities in oil-exposed fish by targeting cardiac-specific genes essential for proper heart development.

Chemical Research in Toxicology↗

USGS2021

Exposure to Deepwater Horizon crude oil increases free cholesterol in larval red drum (Sciaenops ocellatus)

The 2010 Deepwater Horizon oil spill impacted over 2100 km of shoreline along the northern Gulf of Mexico, which coincided with the spawning season of many coastal species, including red drum ( Sciaenops ocellatus ). Red drum develop rapidly and are sensitive to crude oil exposure during the embryonic and larval periods. This study investigates the predictions from recent transcriptomic studies that cholesterol biosynthetic processes are impacted by oil exposure in fish early life stages. We found that red drum larvae exposed for 72-hours to ΣPAH 50 3.55 - 15.45 µg L −1 exhibited significantly increased pericardial area, a cardiotoxicity metric, but the expression of several genes targeted in the cholesterol synthesis pathway was not affected. However, whole-mount staining revealed significant increases in free cholesterol throughout the larval body (ΣPAH 50 4.71 – 16.15 µg L −1 ), and total cholesterol followed an increasing trend (ΣPAH 50 3.55 - 15.45 µg L −1 ). Cholesterol plays a critical role in fish embryo development and ion channel function. Therefore, the disruption of cholesterol homeostasis, as observed here, could play a role in the oil toxicity phenotype observed across many fish species.

Aquatic Toxicology↗