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BioMed Research International
Volume 2015, Article ID 876047, 13 pages
Research Article

Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells

1Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
2Laboratory of Genomic Function Engineering, Department of Life Science, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
3Laboratory of Developmental Engineering, Department of Life Science, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
4Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan
5Division of Food Chemistry, Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan
6Saitama Prefectural Institute of Public Health, Saitama 355-0133, Japan
7Department of Toxicology, Aichi Prefectural Institute of Public Health, Aichi 462-8576, Japan
8Department of Obstetrics and Gynecology, School of Medicine, Tokai University, Kanagawa 259-1193, Japan
9Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
10Department of Pharmacology, School of Medicine, Aichi Medical University, Aichi 480-1195, Japan
11Faculty of Home Economics, Otsuma Women’s University, Tokyo 102-8357, Japan
12Fuji-Oyama Hospital, Shizuoka 410-1326, Japan

Received 15 November 2014; Revised 26 January 2015; Accepted 9 March 2015

Academic Editor: Francesca Pacchierotti

Copyright © 2015 Yoshikazu Arai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The regulation of transcription and genome stability by epigenetic systems are crucial for the proper development of mammalian embryos. Chemicals that disturb epigenetic systems are termed epimutagens. We previously performed chemical screening that focused on heterochromatin formation and DNA methylation status in mouse embryonic stem cells and identified five epimutagens: diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se), and octachlorodipropyl ether (S-421). Here, we used human induced pluripotent stem cells (hiPSCs) to confirm the effects of 20 chemicals, including the five epimutagens, detected at low concentrations in maternal peripheral and cord blood samples. Of note, these individual chemicals did not exhibit epimutagenic activity in hiPSCs. However, because the fetal environment contains various chemicals, we evaluated the effects of combined exposure to chemicals (DEP, Hg, cotinine, Se, and S-421) on hiPSCs. The combined exposure caused a decrease in the number of heterochromatin signals and aberrant DNA methylation status at multiple gene loci in hiPSCs. The combined exposure also affected embryoid body formation and neural differentiation from hiPSCs. Therefore, DEP, Hg, cotinine, Se, and S-421 were defined as an “epimutagen combination” that is effective at low concentrations as detected in maternal peripheral and cord blood.