Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring-Ca2+ overload via IP3R-GRP75-VDAC1 pathway

Ecotoxicol Environ Saf. 2024 Apr 1:274:116218. doi: 10.1016/j.ecoenv.2024.116218. Epub 2024 Mar 15.

Abstract

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Keywords: Cyfluthrin; Mitochondria–ER associated membrane (MAM); Neurobehavioral; Offspring; Pregnancy.

MeSH terms

  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / metabolism
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / drug effects
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Membrane Proteins* / drug effects
  • Membrane Proteins* / metabolism
  • Nitriles* / toxicity
  • Pregnancy
  • Pyrethrins* / toxicity
  • Rats
  • Voltage-Dependent Anion Channel 1 / drug effects
  • Voltage-Dependent Anion Channel 1 / metabolism

Substances

  • cyfluthrin
  • glucose-regulated proteins
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • Nitriles
  • Pyrethrins
  • VDAC1 protein, human
  • Voltage-Dependent Anion Channel 1
  • Itpr3 protein, rat
  • Inositol 1,4,5-Trisphosphate Receptors