Neurotoxicity of a Biopesticide Analog on Zebrafish Larvae at Nanomolar Concentrations

Int J Mol Sci. 2016 Dec 19;17(12):2137. doi: 10.3390/ijms17122137.


Despite the ever-increasing role of pesticides in modern agriculture, their deleterious effects are still underexplored. Here we examine the effect of A6, a pesticide derived from the naturally-occurring α-terthienyl, and structurally related to the endocrine disrupting pesticides anilinopyrimidines, on living zebrafish larvae. We show that both A6 and an anilinopyrimidine, cyprodinyl, decrease larval survival and affect central neurons at micromolar concentrations. Focusing on a superficial and easily observable sensory system, the lateral line system, we found that defects in axonal and sensory cell regeneration can be observed at much lower doses, in the nanomolar range. We also show that A6 accumulates preferentially in lateral line neurons and hair cells. We examined whether A6 affects the expression of putative target genes, and found that genes involved in apoptosis/cell proliferation are down-regulated, as well as genes reflecting estrogen receptor activation, consistent with previous reports that anilinopyrimidines act as endocrine disruptors. On the other hand, canonical targets of endocrine signaling are not affected, suggesting that the neurotoxic effect of A6 may be due to the binding of this compound to a recently identified, neuron-specific estrogen receptor.

Keywords: hair cells; mechanosensory organ; mechanosensory system; posterior lateral line; pyrimidine; α-terthienyl.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biological Control Agents / toxicity*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Endocrine Disruptors / toxicity*
  • Gene Expression Regulation
  • Larva / drug effects*
  • Lateral Line System / drug effects*
  • Mechanoreceptors / drug effects
  • Nerve Regeneration / drug effects*
  • Pyrimidines / toxicity*
  • Pyrimidinones / toxicity*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Thiophenes / chemistry
  • Thiophenes / toxicity*
  • Zebrafish / embryology*


  • 2-(2'-thienyl)-5-(4''-(2''-aminopyrimidyl)thiophene
  • Biological Control Agents
  • Endocrine Disruptors
  • Pyrimidines
  • Pyrimidinones
  • Receptors, Estrogen
  • Thiophenes
  • alpha-terthienyl
  • cyprodinil