Perfluoroheptanoic acid affects amphibian embryogenesis by inducing the phosphorylation of ERK and JNK

• Published in: International journal of molecular medicine Vol. 36; no. 6; pp. 1693 - 1700
• Main Authors: KIM, MIRAN, PARK, MI SEON, SON, JUNGEUN, PARK, INJI, LEE, HYUN-KYUNG, KIM, CHOWON, MIN, BYUNG-HWA, RYOO, JAEWOONG, CHOI, KWANG SHIK, LEE, DONG-SEOK, LEE, HYUN-SHIK
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.12.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Acids; Animals; Blotting, Western; Caproates - toxicity; Carbon; Carcinogenesis; Cellular signal transduction; developmental toxicity; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - embryology; Embryo, Nonmammalian - metabolism; embryogenesis; Extracellular Signal-Regulated MAP Kinases - metabolism; Fluorine; Fluorocarbons - toxicity; Gene expression; Gene Expression Regulation, Developmental - drug effects; Genetic aspects; Health aspects; Heart; Heart - drug effects; Heart - embryology; Heptanoic Acids - toxicity; In Situ Hybridization; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Laboratory animals; Larva - drug effects; Larva - genetics; Larva - metabolism; Liver; Liver - drug effects; Liver - embryology; Liver - pathology; Myocardium - metabolism; Myocardium - pathology; perfluoroalkyl compounds; Perfluorocarbons; Phosphorylation; Phosphorylation - drug effects; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; Studies; teratogenicity; Toxicity; Xenopus; Xenopus laevis - embryology; Xenopus laevis - genetics; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2015.2370

Perfluoroalkyl compounds (PFCs) are globally distributed synthetic compounds that are known to adversely affect human health. Developmental toxicity assessment of PFCs is important to facilitate the evaluation of their environmental impact. In the present study, we assessed the developmental toxicity and teratogenicity of PFCs with different numbers of carbon atoms on Xenopus embryogenesis. An initial frog embryo teratogenicity assay-Xenopus (FETAX) assay was performed that identified perfluorohexanoic (PFHxA) and perfluoroheptanoic (PFHpA) acids as potential teratogens and developmental toxicants. The mechanism underlying this teratogenicity was also investigated by measuring the expression of tissue-specific biomarkers such as phosphotyrosine-binding protein, xPTB (liver); NKX2.5 (heart); and Cyl18 (intestine). Whole-mount in situ hybridization, reverse transcriptase-polymerase chain reaction (RT-PCR), and histologic analyses detected severe defects in the liver and heart following exposure to PFHxA or PFHpA. In addition, immunoblotting revealed that PFHpA significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PFHxA slightly increased these, as compared with the control. These results suggest that PFHxA and PFHpA are developmental toxicants and teratogens, with PFHpA producing more severe effects on liver and heart development through the induction of ERK and JNK phosphorylation.