title: Perfluoroheptanoic acid affects amphibian embryogenesis by inducing the phosphorylation of ERK and JNK.
abstract: 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.
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Kim
authors.affiliation: Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, Republic of Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Park
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jungeun
authors.initials: J
authors.lastname: Son
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Inji
authors.initials: I
authors.lastname: Park
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Chowon
authors.initials: C
authors.lastname: Kim
authors.affiliation: Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, Republic of Korea.
authors.forename: Byung-Hwa
authors.initials: BH
authors.lastname: Min
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Ryoo
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Kwang Shik
authors.initials: KS
authors.lastname: Choi
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.affiliation: ABRC, CMRI, School of Life Sciences, College of Natural Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002208:Caproates / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005466:Fluorocarbons / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006538:Heptanoic Acids / Q000633:toxicity*; D017403:In Situ Hybridization; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
chemical_list: D002208:Caproates; D005466:Fluorocarbons; D006538:Heptanoic Acids; D029867:Xenopus Proteins; C101815:perfluoro-n-heptanoic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C479228:perfluorohexanoic acid