title: miRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol.
abstract: BACKGROUND
  It is known that some environmental chemicals affect the human endocrine system. The harmful effects of endocrine disrupting chemical (EDC) nonylphenol (NP) have been studied since the 1980s. It is known that NP adversely affects physiological functions by mimicking the natural hormone 17 beta-estradiol. In the present study, we analyzed the expression of miRNAs and their target genes in mouse Sertoli TM4 cells to better understand the regulatory roles of miRNAs on Sertoli cells after NP exposure.
  
  
  METHODS
  Mouse TM4 Sertoli cells were treated with NP for 3 or 24 h, and global gene and miRNA expression were analyzed using Agilent mouse whole genome and mouse miRNA v13 arrays.
  
  
  RESULTS
  We identified genes that were > 2-fold differentially expressed in NP-treated cells and control cells (P < 0.05) and analyzed their functions through Gene Ontology analysis. We also identified miRNAs that were differentially expressed in NP-treated and control cells. Of the 186 miRNAs the expression of which differed between NP-treated and control cells, 59 and 147 miRNAs exhibited 1.3-fold increased or decreased expression at 3 and 24 h, respectively. Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. Additionally, comprehensive analysis of predicted target genes for miRNAs showed that the expression of genes with roles in cell proliferation, the cell cycle, and cell death were regulated by miRNA in NP-treated TM4 cells. Levels of expression of the miRNAs miR-135a* and miR-199a-5p were validated by qRT-PCR. Finally, miR-135a* target gene analysis suggests that the generation of reactive oxygen species (ROS) following exposure to NP exposure may be mediated by miR-135a* through regulation of the Wnt/beta-catenin signaling pathway.
  
  
  CONCLUSIONS
  Collectively, these data help to determine NP's actions on mouse TM4 Sertoli cells and increase our understanding of the molecular mechanisms underlying the adverse effects of xenoestrogens on the reproductive system.
authors.affiliation: Division of Research and Development, Korea Institute of Toxicology, 19 Shinsung-ro, Yuseong, Daejeon, 305-343, Korea.
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Oh
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Choi
authors.forename: Se-Myo
authors.initials: SM
authors.lastname: Park
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Kang
authors.forename: Moon-Ju
authors.initials: MJ
authors.lastname: Oh
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Hwang
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009994:Osmolar Concentration; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D052244:Endocrine Disruptors; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; C534780:Mirn199 microRNA, mouse; D047493:PPAR alpha; D010636:Phenols; D012333:RNA, Messenger; C025256:nonylphenol