D-tetramethrin induces cardiac looping failure in zebrafish during embryonic development

Cardiac looping is a crucial process during embryonic development. Abnormalities or failures in cardiac looping can lead to congenital heart defects, thereby affecting normal physiological function. Environmental pollutant exposure is one of the major causes of cardiac looping failure. D-tetramethrin is a hygienic insecticide widely used in households and public places, that can enter the human body through contact, insect transmission, and the food chain, thereby impacting human health. In this study, zebrafish embryos were exposed to different concentrations of D-tetramethrin to analyze its effects on heart development, and oxidative stress levels within the embryos. Additionally, qPCR was employed to analyze the transcription and the expression levels of genes related to heart development and function. The results showed that (1) D-tetramethrin exposure significantly reduced heart rate and increased the distance between the sinus venosus and the bulbus arteriosus (SV-BA), which suggested that D-tetramethrin induced cardiac looping failure and led to abnormal heart function. (2) D-tetramethrin exposure elevated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in zebrafish embryos while decreasing the enzyme activities of key antioxidant stress enzymes, such as catalase (CAT) and superoxide dismutase (SOD). (3) D-tetramethrin exposure resulted in a significant downregulation of the transcription of cardiac looping-related genes (Myh6, Nkx2.5, Tbx2b, Tbx5a, Tnnt2c and Hand2) and heart function-related genes (Gata4, Vmhc and Nppa). Our findings indicate that D-tetramethrin causes the accumulation of ROS, which in turn alters the transcription levels of genes related to cardiac looping, ultimately resulting in cardiac looping failure.