The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine

BMC Genomics. 2015 Oct 30:16:885. doi: 10.1186/s12864-015-2095-y.

Abstract

Background: Environmental factors such as pesticides can cause phenotypic changes in various organisms, including mammals. We studied the effects of the widely used herbicide atrazine (ATZ) on meiosis, a key step of gametogenesis, in male mice.

Methods: Gene expression pattern was analysed by Gene-Chip array. Genome-wide mapping of H3K4me3 marks distribution was done by ChIP-sequencing of testis tissue using Illumina technologies. RT-qPCR was used to validate differentially expressed genes or differential peaks.

Results: We demonstrate that exposure to ATZ reduces testosterone levels and the number of spermatozoa in the epididymis and delays meiosis. Using Gene-Chip and ChIP-Seq analysis of H3K4me3 marks, we found that a broad range of cellular functions, including GTPase activity, mitochondrial function and steroid-hormone metabolism, are affected by ATZ. Furthermore, treated mice display enriched histone H3K4me3 marks in regions of strong recombination (double-strand break sites), within very large genes and reduced marks in the pseudoautosomal region of X chromosome.

Conclusions: Our data demonstrate that atrazine exposure interferes with normal meiosis, which affects spermatozoa production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Atrazine / pharmacology*
  • Binding Sites
  • Cell Survival
  • Chromatin Immunoprecipitation
  • Computational Biology / methods
  • DNA Breaks, Double-Stranded / drug effects
  • Epigenesis, Genetic / drug effects*
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Gonadal Steroid Hormones / metabolism
  • Herbicides / pharmacology*
  • High-Throughput Nucleotide Sequencing
  • Histones / metabolism
  • Male
  • Meiosis / drug effects*
  • Meiosis / genetics*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Nucleotide Motifs
  • Position-Specific Scoring Matrices
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sperm Count
  • Testis / drug effects
  • Testis / metabolism
  • Testosterone / blood

Substances

  • Gonadal Steroid Hormones
  • Herbicides
  • Histones
  • Nr5a2 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Testosterone
  • GTP Phosphohydrolases
  • Atrazine

Associated data

  • GEO/GSE64037