title: Perfluorooctane sulfonate (PFOS) induced embryotoxicity and disruption of cardiogenesis.
abstract: Prenatal exposure to perfluorooctane sulfonate (PFOS) is correlated with birth defects and adverse health effects. However, the mechanisms remain largely unknown. In current study, the embryonic stem cell test (EST) was performed to evaluate the embryotoxicity of PFOS, and embryonic stem cells (ESCs)-derived cardiomyocytes were used as a model of the early stages of heart development to determine the developmental toxicity of PFOS. One validated endpoint and three molecular endpoints were observed to ensure accurate evaluation of toxicity. According to the criteria of the EST, PFOS was classified as weak embryotoxic. In addition, a cascade of genes related to normal cardiac development was examined at three different time points to monitor cardiogenesis. We found that PFOS significantly interfered with gene expression during cardiogenesis, especially on Nkx2.5 and Myl4. Further, PFOS reduced ATP production in ESCs-derived cardiomyocytes, together with PFOS induced apoptosis, could explain the reduction in beating ability. PFOS-induced reactive oxygen species (ROS) accumulated within cells, which was accompanied by an interfering expression of apoptosis-related genes, ultimately leading to apoptosis. In conclusion, PFOS altered the expression of crucial genes, reduced ATP production, induced ROS, and stimulated apoptosis during the early stages of cardiogenesis; these effects may result in poor developmental outcomes.
authors.affiliation: College of Public Health, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China. mishua_@hotmail.com
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yu
authors.forename: Lixin
authors.initials: L
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000826:Animal Testing Alternatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D017382:Reactive Oxygen Species; D013723:Teratogens; C076994:perfluorooctane sulfonic acid