PMID- 33297007 OWN - NLM STAT- MEDLINE DCOM- 20201221 LR - 20201221 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 263 DP - 2021 Jan TI - Comparative cytotoxicity studies of halophenolic disinfection byproducts using human extended pluripotent stem cells. PG - 127899 LID - S0045-6535(20)32094-4 [pii] LID - 10.1016/j.chemosphere.2020.127899 [doi] AB - 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP) are a new class of halophenolic disinfection byproducts (DBPs) which have been widely detected in drinking water. In recent years, their developmental toxicity has got increasing public attention due to their potential toxic effects on embryo development towards lower organisms. Nonetheless, the application of human embryos for embryonic toxicologic studies is rendered by ethical and moral considerations, as well as the technical barrier to sustaining normal development beyond a few days. Human extended pluripotent stem (EPS) cells (novel totipotent-like stem cells) represent a much more appropriate cellular model for studying human embryo development. In this study, we utilized human EPS cells to study the developmental toxicity of TCP, TBP and TIP, respectively. All three halophenolic DBPs showed cytotoxicity against human EPS cells in an obvious dose-dependent manner, among which TIP was the most cytotoxic one. Notably, the expression of pluripotent genes in human EPS cells significantly declined after 2,4,6-trihalophenol exposure. Meanwhile, 2,4,6-trihalophenol exposure promoted ectodermal differentiation of human EPS cells in an embryoid bodies (EBs) differentiation assay, while both endodermal and mesodermal differentiation were impaired. These results implied that phenolic halogenated DBPs have specific effects on human embryo development even in the early stage of pregnancy. In summary, we applied human EPS cells as a novel research model for human embryo developmental toxicity study of environmental pollutants, and demonstrated the toxicity of phenolic halogenated DBPs on early embryo development of human beings. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Liu, Yujie AU - Liu Y AD - State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China. FAU - Zhu, Dicong AU - Zhu D AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhao, Zhihua AU - Zhao Z AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhou, Qing AU - Zhou Q AD - State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China. FAU - Pan, Yang AU - Pan Y AD - State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China. FAU - Shi, Wei AU - Shi W AD - State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China. FAU - Qiu, Jingfan AU - Qiu J AD - Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen Biology, Nanjing Medical University, Nanjing, 211166, China. Electronic address: qiujingfan@njmu.edu.cn. FAU - Yang, Yang AU - Yang Y AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China. Electronic address: yangyang11@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20200815 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Disinfectants) RN - 0 (Drinking Water) RN - 0 (Water Pollutants, Chemical) SB - IM MH - *Disinfectants MH - Disinfection MH - *Drinking Water MH - Halogenation MH - Humans MH - *Pluripotent Stem Cells/chemistry MH - *Water Pollutants, Chemical/analysis/toxicity MH - *Water Purification OTO - NOTNLM OT - Developmental toxicity OT - Differentiation potency OT - Halophenolic disinfection byproducts OT - Human extended pluripotent stem cells COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/12/11 06:00 MHDA- 2020/12/22 06:00 CRDT- 2020/12/10 01:01 PHST- 2020/05/19 00:00 [received] PHST- 2020/07/30 00:00 [revised] PHST- 2020/08/01 00:00 [accepted] PHST- 2020/12/10 01:01 [entrez] PHST- 2020/12/11 06:00 [pubmed] PHST- 2020/12/22 06:00 [medline] AID - S0045-6535(20)32094-4 [pii] AID - 10.1016/j.chemosphere.2020.127899 [doi] PST - ppublish SO - Chemosphere. 2021 Jan;263:127899. doi: 10.1016/j.chemosphere.2020.127899. Epub 2020 Aug 15.