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Potential new targets involved in 1,3-dinitrobenzene induced testicular toxicity

Sophie Ludwig1, Helen Tinwell, David Rouquié

  • 1Bayer SAS, Department of Research Toxicology, 355 rue Dostoïevski, 06903 Sophia-Antipolis, France.

Toxicology Letters
|July 31, 2012
PubMed

Insights

1,3-Dinitrobenzene (DNB) causes testicular damage by inducing germ cell apoptosis and altering cell cycle progression. This chemical also impacts steroid hormone biosynthesis, suggesting potential endocrine disruption alongside direct testicular toxicity.

Area of Science:

  • Toxicology
  • Reproductive Biology
  • Molecular Biology

Background:

  • 1,3-Dinitrobenzene (DNB) is known to induce testicular injury and germ cell apoptosis in rodents.
  • The precise mechanisms underlying DNB-induced testicular toxicity remain poorly understood.

Purpose of the Study:

  • To elucidate the pathogenesis of testicular effects induced by 1,3-Dinitrobenzene (DNB).
  • To investigate the impact of DNB on testicular cell cycle, apoptosis, and steroidogenesis.

Main Methods:

  • Standard toxicological assessments and molecular tools were employed.
  • Global transcriptomics analysis was performed on rat testes following DNB exposure.
  • In vitro H295R steroidogenesis assay was utilized to confirm steroid hormone effects.

Main Results:

  • Multiple oral doses of DNB (≥4mg/kg/day) caused significant testicular lesions in rats.
  • Transcriptomics revealed alterations in cell cycle progression (e.g., polo-like kinase genes) and cell death pathways.
  • Single DNB dose did not cause adverse changes, but multiple doses affected plasma testosterone and testicular steroidogenesis gene expression, confirmed in vitro.

Conclusions:

  • 1,3-Dinitrobenzene (DNB) induces testicular apoptosis and interferes with the cell cycle.
  • DNB exposure modulates steroid hormone biosynthesis, indicating potential endocrine system interference.
  • The contribution of endocrine changes to DNB-induced testicular lesions requires further investigation.

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