miR-137 and miR-141 regulate tail defects in zebrafish embryos caused by triphenyl phosphate (TPHP)

Abstract

Exposure to triphenyl phosphate (TPHP), an organophosphate flame retardants (OPFRs), caused developmental toxicity in zebrafish embryos. However, the underlying molecular mechanism at the epigenetic level is largely unknown. Based on developmental toxicity (i.e., mortality and malformation), we measured expression levels of mRNA genes and their targeted miRNA in zebrafish embryos exposed to TPHP. As a result, TPHP caused developmental delay beginning at the 17-somite stage linking to detrimental effects in the tail and even embryonic mortality. Abnormal tail development was found to be associated with down-regulation of mmp9 and sox9b in both qRT-PCR and whole in-situ hybridization analysis. Also, we identified two microRNAs (i.e., miR-137 and miR-141) and observed their differential over-expression in TPHP-exposed zebrafish embryos. In the microinjection of miR-137 and miR-141 inhibitors, the reduced expression of mmp9 and sox9b upon TPHP exposure was compensated, indicating that epigenetic deregulation of miRNAs modulated putative genes involved in phenotypic tail defects triggered by TPHP in developing zebrafish embryos. This study provides insight for future mechanistic research using teleost fish on function of miRNAs in environmental toxicology.

Keywords: Tail malformation; Toxicity; Triphenyl phosphate; Zebrafish; microRNA.