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Updated: Aug 30, 2025
Using Chicken Embryo as a Powerful Tool in Assessment of Developmental Cardiotoxicities
Published on: March 21, 2021
Perfluorooctanoic acid-induced developmental cardiotoxicity in chicken embryo: Roles of miR-490-5p
Yajie Guo1, Junhua Yuan2, Hao Ni1
1Department of Toxicology, School of Public Health, Qingdao University, China.
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.
Insights
Perfluorooctanoic acid (PFOA) causes developmental heart toxicity. This study identifies miR-490-5p as a key player in PFOA-induced cardiotoxicity, affecting SNAP91 and LYPD6 gene expression in chicken embryos.
Area of Science:
- Environmental toxicology
- Developmental biology
- Molecular toxicology
Background:
- Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant linked to developmental toxicities, particularly affecting the heart.
- While peroxisome-proliferation activated receptor alpha (PPARα) is a known PFOA target, PPARα-independent mechanisms of toxicity are increasingly recognized.
- Understanding the specific molecular pathways underlying PFOA-induced developmental cardiotoxicity is crucial for risk assessment.
Purpose of the Study:
- To elucidate the molecular mechanisms of PFOA-induced developmental cardiotoxicity in chicken embryos.
- To identify specific microRNAs (miRNAs) and their downstream targets involved in PFOA's cardiac effects.
- To investigate the functional role of identified molecular players in PFOA-induced cardiotoxicity.
Main Methods:
- RNA sequencing (RNA-seq) was employed to analyze gene and miRNA expression profiles in chicken hearts developmentally exposed to PFOA.
- Quantitative real-time PCR (RT-PCR) and Western blotting were used to validate the expression levels of selected miRNAs and their target genes.
- Lentiviral vectors were utilized to overexpress and silence miR-490-5p in developing chicken embryos to assess functional impacts.
Main Results:
- Developmental exposure to PFOA significantly altered the expression of 21 miRNAs and 1142 mRNAs in chicken embryo hearts.
- miR-490-5p was identified as a significantly dysregulated miRNA following PFOA exposure.
- Overexpression of miR-490-5p mimicked PFOA-induced cardiotoxicity phenotypes, while its silencing alleviated these effects, implicating miR-490-5p in PFOA's cardiac toxicity.
- Downstream targets of miR-490-5p, Synaptosome associated protein 91 (SNAP91) and LY6/PLAUR domain containing 6 (LYPD6), showed altered expression consistent with miR-490-5p regulation.
Conclusions:
- miR-490-5p plays a critical role in PFOA-induced developmental cardiotoxicity in chicken embryos.
- The downstream targets SNAP91 and LYPD6 are implicated in the mechanism of PFOA-induced cardiac developmental toxicity.
- These findings contribute to a deeper understanding of the molecular pathways mediating PFOA's adverse effects on heart development.
