title: Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage.
abstract: Pentachlorophenol (PCP) is a prevalent pollutant in the environment and has been demonstrated to be a serious toxicant to humans and animals. However, little is known regarding the molecular mechanism underlying its toxic effects on vertebrate early development. To explore the impacts and underlying mechanisms of PCP on early development, zebrafish (Danio rerio) embryos were exposed to PCP at concentrations of 0, 20 and 50 μg/L, and microscopic observation and cDNA microarray analysis were subsequently conducted at gastrulation stage. The morphological observations revealed that PCP caused a developmental delay of zebrafish embryos in a concentration-dependent manner. Transcriptomic data showed that 50 μg/L PCP treatment resulted in significant changes in gene expression level, and the genes involved in energy metabolism and cell behavior were identified based on gene functional enrichment analysis. The energy production of embryos was influenced by PCP via the activation of glycolysis along with the inhibition of oxidative phosphorylation (OXPHOS). The results suggested that PCP acts as an inhibitor of OXPHOS at 8 hpf (hours postfertilization). Consistent with the activated glycolysis, the cell cycle activity of PCP-treated embryos was higher than the controls. These characteristics are similar to the Warburg effect, which occurs in human tumors. The microinjection of exogenous ATP confirmed that an additional energy supply could rescue PCP-treated embryos from the developmental delay due to the energy deficit. Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay.
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Model Animal for Disease Study, Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing 210061, China; State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key Laboratory of Model Animal for Disease Study, Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Zhangji
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Key Laboratory of Model Animal for Disease Study, Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai 200092, China. Electronic address: yindq@tongji.edu.cn.
authors.forename: Daqiang
authors.initials: D
authors.lastname: Yin
authors.affiliation: Key Laboratory of Model Animal for Disease Study, Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: qingshun@nju.edu.cn.
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005775:Gastrula / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D054262:Gastrulation / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005838:Genotype; D006019:Glycolysis / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010416:Pentachlorophenol / Q000633:toxicity*; D010641:Phenotype; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D000255:Adenosine Triphosphate; D010416:Pentachlorophenol
keywords: Gastrulation; Glycolysis; Oxidative phosphorylation; Pentachlorophenol; Warburg effect; Zebrafish