1. Academic Validation
  2. Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring-Ca2+ overload via IP3R-GRP75-VDAC1 pathway

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

  • Ecotoxicol Environ Saf. 2024 Mar 15:274:116218. doi: 10.1016/j.ecoenv.2024.116218.
Haoxuan Gao 1 Mi Tian 1 Xiaozhe Geng 1 Ji Zhao 1 Yanan Song 1 Bing Wu 1 Xueyan Tian 1 Yong Yang 2 Wensi Ni 3 Huifang Yang 4
Affiliations

Affiliations

  • 1 School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
  • 2 Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
  • 3 School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China. Electronic address: [email protected].
  • 4 School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China. Electronic address: [email protected].
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.

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