Cardiotoxicity of mycotoxin citrinin and involvement of microRNA-138 in zebrafish embryos.
Citrinin (CTN) is a fungal secondary metabolite that contaminates various foodstuffs and animal feeds; it also exhibits organotoxicity in several animal models. In this study, the zebrafish was used to elucidate the mechanism of CTN cardiotoxicity in developing embryos. Following CTN administration, the gross morphology of the embryonic heart was apparently altered, including heart malformation, pericardial edema, and red blood accumulation. Whole-mount immunostaining and histological analysis of ventricle and atrium indicated incorrect heart looping and reduced size of heart chambers. From the perspective of cardiac function, the heartbeat and blood flow rate of embryos were significantly decreased in the presence of CTN. CTN also modulated the expression of tbx2a and jun B genes, but not that of bmp4 and nkx2.5. Furthermore, the heart areas of CTN-exposed embryos demonstrated an elevated levels of aldh1a2 and cspg2 messenger RNA; these 2 cardiac-related genes are known to be involved in retinoic acid (RA) pathway as well as downstream targets of microRNA-138 (miR-138) in zebrafish. CTN treatment also downregulated the expression of miR-138. Moreover, overexpression of miR-138 was able to rescue the heart defects generated by CTN. These results support the notion that CTN exposure has a severe impact on heart development, affecting heart morphogenesis through the dysregulation of miR-138, RA signaling, and tbx2a.
* Institute of Medicine.
Ting-Shuan
TS
Wu
Jiann-Jou
JJ
Yang
Feng-Yih
FY
Yu
Biing-Hui
BH
Liu
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D019521:Body Patterning; D002953:Citrinin / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006339:Heart Rate / Q000187:drug effects; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*
D035683:MicroRNAs; D002953:Citrinin; D014212:Tretinoin
cardiotoxicity; citrinin; microRNA-138; mycotoxin.; zebrafish embryos