TY - JOUR A2 - Pacchierotti, Francesca AU - Arai, Yoshikazu AU - Hayakawa, Koji AU - Arai, Daisuke AU - Ito, Rie AU - Iwasaki, Yusuke AU - Saito, Koichi AU - Akutsu, Kazuhiko AU - Takatori, Satoshi AU - Ishii, Rie AU - Hayashi, Rumiko AU - Izumi, Shun-Ichiro AU - Sugino, Norihiro AU - Kondo, Fumio AU - Horie, Masakazu AU - Nakazawa, Hiroyuki AU - Makino, Tsunehisa AU - Hirosawa, Mitsuko AU - Shiota, Kunio AU - Ohgane, Jun PY - 2015 DA - 2015/08/03 TI - Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells SP - 876047 VL - 2015 AB - 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. SN - 2314-6133 UR - https://doi.org/10.1155/2015/876047 DO - 10.1155/2015/876047 JF - BioMed Research International PB - Hindawi Publishing Corporation KW - ER -