Ochratoxin A (OTA) is a fungal secondary metabolite widely detected in food and feed sources, and this natural chemical also shows various toxicological effects on humans and animals. In the present study, zebrafish embryos were used to investigate the developmental toxicity of OTA. When the embryos were treated with OTA from 6 hour post-fertilization (hpf) to 72 hpf, the LC50 value was found to be 1 �M. The OTA treatment resulted in an incorrect arrangement and reduced size of ventricular and atrial chambers in the heart area of zebrafish embryos. Furthermore, the heart tube looping index was also significantly increased to 1.5-fold of the control level. From the perspective of cardiac function, the heartbeat and blood flow of embryos were significantly decreased in the presence of OTA. OTA at the concentration of 1 �M significantly decreased the heart beat from 152.1 � 6.5 to 110.9 � 13.3/min, and the red blood cells accumulated in the pericardial cavity of transgenic embryos (gata1:dsRed). In order to investigate the molecular mechanism associated with OTA-induced heart malformation, both next generation sequencing technology and DNA microarray were applied to reveal the microRNA and messenger RNA profiles after OTA administration. The levels of several microRNAs, including dre-miR-129, dre-miR 2185, dre-miR 219, dre-miR-462 and dre-miR-738, were all dramatically modified; we also found that members in CCN family were down-regulated in the presence of OTA. These results suggest that OTA damages the cardiac structure and function of early developing embryos and specific microRNAs may play a role in OTA-induced toxicity.

Toxic effects of ochratoxin A on the developing heart of zebrafish embryos

248th National Meeting (2014)

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