Evaluation of the testicular toxicity of prenatal exposure to bisphenol A based on microarray analysis combined with MeSH annotation

J Toxicol Sci. 2012;37(3):539-48. doi: 10.2131/jts.37.539.

Abstract

Bisphenol A (BPA) is known to be an endocrine disruptor that affects the development of reproductive system. The aim of the present study was to investigate a group of testicular genes dysregulated by prenatal exposure to BPA. Pregnant ICR mice were treated with BPA by subcutaneous administration on days 7 and 14 of pregnancy. Tissue and blood samples were collected from 6-week-old male offspring. Testes were subjected to gene expression analysis using a testis-specific microarray (Testis2), consisting of 2,482 mouse cDNA clones annotated with Medical Subject Headings (MeSH) terms indicative of testicular components and functions. To interpret the microarray data, we used the MeSH terms significantly associated with the altered genes. As a result, MeSH terms related to androgens and Sertoli cells were extracted in BPA-treated groups. Among the genes related to Sertoli cells, downregulation of Msi1h, Ncoa1, Nid1, Hspb2, and Gata6 were detected in the testis of mice treated with BPA (twice administered 50 mg/kg). The MeSH terms associated with this group of genes may provide useful means to interpret the testicular toxicity of BPA. This article concludes that prenatal BPA exposure downregulates expression of genes associated with Sertoli cell function and affects the reproductive function of male offspring. Additionally, a method using MeSH to extract a group of genes was useful for predicting the testicular and reproductive toxicity of prenatal BPA exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Down-Regulation
  • Endocrine Disruptors / toxicity
  • Female
  • GATA6 Transcription Factor / genetics
  • GATA6 Transcription Factor / metabolism
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism
  • Male
  • Medical Subject Headings*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Receptor Coactivator 1 / genetics
  • Nuclear Receptor Coactivator 1 / metabolism
  • Oligonucleotide Array Sequence Analysis / methods*
  • Organ Size
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Reproduction / drug effects
  • Sertoli Cells / drug effects
  • Sertoli Cells / metabolism
  • Sertoli Cells / pathology
  • Spermatozoa / drug effects
  • Spermatozoa / physiology
  • Testis / drug effects
  • Testis / physiopathology*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • GATA6 Transcription Factor
  • Gata6 protein, mouse
  • HSP27 Heat-Shock Proteins
  • Hspb2 protein, mouse
  • Membrane Glycoproteins
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • Phenols
  • RNA-Binding Proteins
  • nidogen
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1
  • bisphenol A