In vivo evaluation and comparison of developmental toxicity and teratogenicity of perfluoroalkyl compounds using Xenopus embryos |
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Authors: | Miran Kim Jungeun Son Mi Seon Park Yurim Ji Soomin Chae Changduk Jun Jong-Sup Bae Taek Kyu Kwon Yun-Sik Choo Hosung Yoon Duhak Yoon Jaewoong Ryoo Sang-Hyun Kim Mae-Ja Park Hyun-Shik Lee |
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Institution: | 1. ABRC, CMRI, School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, South Korea;2. Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, South Korea;3. Immune Synapse Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea;4. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea;5. Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, South Korea;6. Department of Animal Science, Kyungpook National University, Sangju, Kyungpook 742-711, South Korea;g Department of Pharmacology, College of Medicine, Kyungpook National University, Daegu 702-701, South Korea;h Department of Anatomy, College of Medicine, Kyungpook National University, Daegu 702-701, South Korea |
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Abstract: | Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8–11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs), and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects. |
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Keywords: | Perfluoroalkyl compounds Comparative toxicology Developmental toxicity Teratogenecity Xenopus |
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