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With the increasing use of mycophenolic acid(MPA)in solid organ transplantation,some clinical studies indicate that it is also a human teratogen.However,it is unknown by which mechanism MPA acts as a teratogen.MPA was the selective blocker of de novo purine synthesis and its immunosuppressive effect is mediated by inhibition of inosine monophosphate dehydrogenase(IMPDH),which could be a target for MPA-induced toxicity as well.The aim of our study was to examine the direct influence of MPA exposure in zebrafish(Danio rerio)embryos.Morphological defects including tail curvature and severe pericardial edema in zebrafish embryos caused by MPA(3.7-11.1μM)were found in a dose-dependent manner.The teratogenic index(LC25/NOAEL ratio)was 16,which indicated the MPA as a teratogen.Q-PCR analysis revealed that the expression level of impdh1b and impdh2 were significantly reduced by MPA treatment at 8 μM(equals to LC25 level).All the toxic effects could be partially reversed by the addition of 33.3 μM guanosine.Our results indicated that MPA impairs development of zebrafish embryos via inhibition of impdh activity,which subsequently caused a guanosine nucleotide depletion in vivo.