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Fine particulate matter reduces the pluripotency and proliferation of human embryonic stem cells through ROS induced AKT and ERK signaling pathway.
- Source :
-
Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2020 Sep; Vol. 96, pp. 231-240. Date of Electronic Publication: 2020 Jul 31. - Publication Year :
- 2020
-
Abstract
- Epidemiological investigations have found that air fine particulate matter (PM) exposure not only causes respiratory and cardiovascular diseases in adults and children, but also affects embryonic development during pregnancy, leading to poor pregnancy outcomes. However, its exact molecular mechanism is still unclear. In this study, human embryonic stem cells (hESCs) were treated with PM at different concentrations then the morphology and proliferation capacity were measured. The mRNA and protein expression of NANOG and OCT4 were detected using quantitative PCR, immunofluorescence, western blotting, and flow cytometry. Reactive oxygen species (ROS) generation and AKT/ERK activation were also measured. Meanwhile, changes in ROS, the expression of NANOG, OCT4, and the AKT/ERK pathways were measured in the hESCs with or without pretreatment of ROS scavenger N-acetylcysteine (NAC) prior to PM exposure. After PM exposure, the proliferation capacity and expression of OCT4 and NANOG at the mRNA and protein levels were downregulated. The ROS level in the hESCs increased after PM exposure, but this increase in ROS was attenuated by pretreatment with NAC. Further analysis showed that the levels of phosphorylated AKT and ERK increased after PM exposure. After pretreatment with NAC, the phosphorylation levels of AKT and ERK, which are crucial for regulating the proliferation, pluripotency, and differentiation of hESC, were significantly attenuated compared with the non-NAC pretreated exposure group. These results suggest that PM exposure may reduce the proliferation and pluripotency of hESC through ROS-mediated AKT/ERK pathways, thereby affecting the long-term development of embryos.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Differentiation drug effects
Cell Line
Cell Proliferation drug effects
Human Embryonic Stem Cells cytology
Human Embryonic Stem Cells metabolism
Humans
MAP Kinase Signaling System drug effects
Nanog Homeobox Protein genetics
Nanog Homeobox Protein metabolism
Octamer Transcription Factor-3 genetics
Octamer Transcription Factor-3 metabolism
Proto-Oncogene Proteins c-akt metabolism
Reactive Oxygen Species metabolism
Air Pollutants toxicity
Human Embryonic Stem Cells drug effects
Particulate Matter toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1873-1708
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- Reproductive toxicology (Elmsford, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 32745510
- Full Text :
- https://doi.org/10.1016/j.reprotox.2020.07.010