Differential responses of GC‑1 spermatogonia cells to high and low doses of bisphenol A

Mol Med Rep. 2018 Sep;18(3):3034-3040. doi: 10.3892/mmr.2018.9256. Epub 2018 Jul 6.

Abstract

Bisphenol A (BPA) is an environmental endocrine disruptor. The exact effect of BPA on spermatogenesis and the specific epigenetic effects on mouse spermatogonia remain to be elucidated. The present study exposed the GC‑1 spermatogonial cell line to a series of differing BPA concentrations and examined the subsequent effects on cell proliferation, mitogen activated protein kinase (MAPK) signaling, DNA and histone methylation. A Cell Counting Kit‑8 assay revealed that BPA significantly inhibited cell growth at the concentration of 10 µg/ml, however no significant alterations were detected at lower BPA doses. The global DNA methylation levels were reduced at the dose of 10 µg/ml of BPA, via detection of 5‑methylcytosine using a dot blot. The protein and mRNA expression levels of DNA methyltransferase (DNMT) 1 were decreased at 10 and 1 µg/ml of BPA, detected via western blotting and reverse transcription‑quantitative polymerase chain reaction, respectively. The global levels of H3K27me3 was decreased at 10 µg/ml BPA, detected via western blotting. Increased phosphorylation of p38 and decreased phosphorylation of extracellular signal‑regulated kinases 1/2 were observed at 10 and 1 µg/ml BPA. The results demonstrated that high and low doses of BPA exposure exhibit differential effects on cell growth, global DNA methylation, histone H3K9Me3 and H3K27Me3 levels and additionally affect the MAPK signaling pathways.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • DNA Methylation
  • Dose-Response Relationship, Drug
  • Epigenesis, Genetic
  • Gene Expression Regulation / drug effects
  • Histones / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Methylation
  • Mice
  • Phenols / pharmacology*
  • Spermatogonia / drug effects*
  • Spermatogonia / metabolism*

Substances

  • Benzhydryl Compounds
  • Histones
  • Phenols
  • bisphenol A