Perfluorooctanoic acid-induced developmental cardiotoxicity in chicken embryo: Roles of miR-490-5p

Abstract

Perfluorooctanoic acid (PFOA) could induce developmental toxicities, affecting various organs, including the heart. Although peroxisome-proliferation activated receptor alpha (PPARα) had been identified as a major target of PFOA, PPARα-independent effects are frequently reported. To further elucidate the mechanism of toxicity in PFOA-induced developmental cardiotoxicity, RNA-seq analysis was performed in hatchling chicken hearts developmentally exposed to vehicle or 2 mg/kg (egg weight) PFOA. RT-PCR and western blotting were then performed to confirm the identified potential targets. Furthermore, lentivirus was designed to overexpress and silence identified target miRNA in developing chicken embryo, and the resulting phenotypes were investigated. 21 miRNAs and 1142 mRNAs were identified to be affected by developmental exposure to PFOA in chicken embryo hearts. Among the identified differentially expressed miRNAs, miR-490-5p was confirmed to be significantly affected by PFOA exposure, along with its downstream targets, Synaptosome associated protein 91 (SNAP91) and LY6/PLAUR domain containing 6 (LYPD6), as indicated by RT-PCR and western blotting results. Lentivirus overexpressing miR-490-5p mimicked the phenotype induced by PFOA exposure, while lentivirus silencing miR-490-5p alleviated PFOA-induced changes. Similar patterns were also observed in the expression of downstream target genes, SNAP91 and LYPD6. In summary, miR-490-5p and its downstream genes, SNAP91 and LYPD6 are associated with PFOA-induced developmental cardiotoxicity in chicken embryo, which might help to further elucidate the mechanism of PFOA-induced developmental cardiotoxicity.

Keywords: Chicken embryo; Developmental cardiotoxicity; Perfluorooctanoic acid; miRNA-490-5p.