Microarray analysis of 6-mercaptopurine-induced-toxicity-related genes and microRNAs in the rat placenta

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Author(s)

    • HORII Ikuo
    • Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University
    • YOSHIDA Takemi
    • Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University

Abstract

MicroRNAs (miRNAs) are small single-stranded RNAs of 19-25 nucleotides and are important in posttranscriptional regulation of genes. Recently, the role of miRNAs in toxicity incidence is reported to be a regulator of key-stopper of gene expression, however the detailed mechanism of miRNAs is not well known yet. 6-Mercaptopurine (6-MP), the anti-leukemic and immunosuppressive drug, produced teratogenicity and pregnancy loss. We focused on the placenta to evaluate toxicity in embryo/fetal development produced by 6-MP treatment. MiRNA expression in the placenta was analyzed by miRNA microarray. Fifteen miRNAs were upregulated on GD13 and 5 miRNAs were downregulated on GD15 in 6-MP treatment rat placentas. Some miRNAs may have functions in apoptosis (miR-195, miR-21, miR-29c and miR-34a), inflammation (miR-146b), and ischemia (miR-144 and miR-451). In the maternal plasma, expression of miR-144 was significantly reduced by 6-MP treatment when examined by real-time RT-PCR. We determined toxicity-related gene expression in the rat placenta. Gene expression analysis was carried out by DNA oligo microarray using rat placenta total RNAs. Compared between predicted targets of miRNAs and microarray data in 6-MP-treated rat placenta, expressions of hormone receptor genes (estrogen receptor 1; <i>Esr1</i>, progesterone receptor; <i>Pgr</i>, and prolactin receptor; <i>Prlr</i>), xanthine oxidase (<i>Xdh</i>), <i>Slc38a5</i> and <i>Phlda2</i> genes were changed. The histopathologically found increase in trophoblastic giant cells and reduced placental growth by 6-MP treatment were well correlated to these gene expressions. These data suggest that some miRNAs may link to toxicological reactions in 6-MP-induced placental toxicity.

Journal

  • The Journal of Toxicological Sciences

    The Journal of Toxicological Sciences 38(1), 159-167, 2013-02-01

    The Japanese Society of Toxicology

References:  47

Codes

  • NII Article ID (NAID)
    10031138739
  • NII NACSIS-CAT ID (NCID)
    AN00002808
  • Text Lang
    ENG
  • Article Type
    NOT
  • ISSN
    03881350
  • NDL Article ID
    024284380
  • NDL Call No.
    Z19-1022
  • Data Source
    CJP  NDL  J-STAGE 
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