MiR-301b-3p/3584-5p enhances low-dose mono-n-butyl phthalate (MBP)-induced proliferation by targeting Rasd1 in Sertoli cells

Toxicol In Vitro. 2018 Mar:47:79-88. doi: 10.1016/j.tiv.2017.11.009. Epub 2017 Nov 21.

Abstract

To investigate the possible molecular mechanism of low concentration plasticizer mono-n-butyl phthalate (MBP) -induced juvenile Sertoli cells (SCs) proliferation, we evaluated global alterations of miRNA and mRNA expression in rat SCs treated with 0.1mM MBP. Microarray analysis revealed that miR-3584-5p and miR-301b-3p were up-regulated and their common target gene Dexamethasone-induced Ras-related protein 1 (Rasd1) was down-regulated. Further work suggested that SCs proliferation induced by low concentration MBP in vitro might be mediated by Rasd1 regulating ERK1/2 signaling pathway. The present study is first to investigate the effect of low-dose MBP on SCs proliferation and may enhance our understanding on the modes of action of low concentration MBP on male reproductive system. We hope the results will contribute to explain the causes of precocious puberty and testicular tumors induced by exogenous chemicals.

Keywords: Cell proliferation; Dexamethasone-induced Ras-related protein 1 (Rasd1); Mono-n-butyl phthalate (MBP); Sertoli cells (SCs); miR-301b-3p; miR-3584-5p.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Computational Biology
  • Databases, Genetic
  • Endocrine Disruptors / toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Gene Regulatory Networks / drug effects
  • Genes, Reporter / drug effects
  • Male
  • MicroRNAs / agonists*
  • MicroRNAs / metabolism
  • Osmolar Concentration
  • Phthalic Acids / toxicity*
  • Plasticizers / toxicity*
  • Rats, Sprague-Dawley
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Testis / cytology
  • Testis / drug effects
  • Testis / growth & development
  • Testis / metabolism
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Endocrine Disruptors
  • MIRN301 microRNA, rat
  • MIRN3584 microRNA, rat
  • MicroRNAs
  • Phthalic Acids
  • Plasticizers
  • Rasd1 protein, rat
  • ras Proteins
  • monobutyl phthalate