The role of PPAR alpha in perfluorooctanoic acid induced developmental cardiotoxicity and l-carnitine mediated protection-Results of in ovo gene silencing

- PFOA-induced heart rate change is independent of PPAR alpha.
- PFOA-induced heart morphological change is dependent on PPAR alpha.
- l-carnitine mediated protective effects do not require PPAR alpha.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant. This study established an in ovo peroxisome proliferator-activated receptor alpha (PPAR alpha) silencing model in chicken embryo heart, and investigated the role of PPAR alpha in PFOA induced developmental cardiotoxicity. The in ovo silencing was achieved by introducing lentivirus expressing PPAR alpha siRNA into ED2 chicken embryo via microinjection (0.05 ul/g egg weight). Transfection efficacy was confirmed by fluorescent microscopy and western blotting. To assess the developmental cardiotoxicity, cardiac function (heart rate) and morphology (right ventricular wall thickness) were measured in D1 hatchling chickens. 2 mg/kg (egg weight) PFOA exposure at ED0 induced significant elevation of heart rate and thinning of right ventricular wall thickness in D1 hatchling chickens. PPAR alpha silencing did not prevent PFOA-induced elevation of heart rate; however, it did significantly increase the right ventricular wall thickness as compared to PFOA exposed animals. Meanwhile, PPAR alpha silencing did not abolish the protective effects exerted by exposure to 100 mg/kg (egg weight) l-carnitine. In conclusion, PFOA-induced heart rate elevation is likely PPAR alpha independent, while the right ventricular wall thinning seems to be PPAR alpha dependent. The protective effects of l-carnitine do not require PPAR alpha.