Emerging Disinfection Byproduct 2,6-Dichlorobenzoquinone-Induced Cardiovascular Developmental Toxicity of Embryonic Zebrafish and Larvae: Imaging and Transcriptome Analysis

Epidemiological studies have observed the potential association
of water disinfection byproduct (DBP) exposure with cardiac defects.
Aromatic DBPs represent a significant portion of total DBPs, but their
effects on cardiovascular development are unclear. In this study,
we examined the effects of an aromatic DBP, 2,6-dichlorobenzoquinone
(DCBQ), on the cardiovascular development of zebrafish embryos. After
exposure to 2, 4, and 8 μM DCBQ, morphological images of growing
zebrafish embryos clearly showed cardiovascular malformation. Fluorescent
images of transgenic zebrafish strains with fluorescently labeled
heart and blood vessels show that DCBQ exposure resulted in deformed
atrium–ventricle looping, degenerated abdomen and trunk vessels,
pericardial edema, and decreased blood flow. Furthermore, the expression
of the marker gene myl7 (essential for the differentiation
and motility of cardiomyocytes) was inhibited in a dose-dependent
manner by DCBQ exposure. Finally, transcriptome analysis found that
in the 4 μM DCBQ exposure group, the numbers of differentially
expressed genes (DEGs) were 113 (50 upregulated and 63 downregulated)
at 24 hpf, 2123 (762 upregulated and 1361 downregulated) at 48 hpf,
and 61 (11 upregulated and 50 downregulated) at 120 hpf; in the 8
μM DCBQ exposure group, the number of DEGs was 1407 (647 upregulated
and 760 downregulated) at 120 hpf. The FoxO signaling pathway was
significantly altered. The in vivo results demonstrate
the effects of 2,6-DCBQ (0–8 μM) on cardiovascular development,
contributing to the understanding of the developmental toxicity of
aromatic DBP halobenzoquinones (HBQs).