1. Academic Validation
  2. Perinatal exposure to nonylphenol induces microglia-mediated nitric oxide and prostaglandin E2 production in offspring hippocampus

Perinatal exposure to nonylphenol induces microglia-mediated nitric oxide and prostaglandin E2 production in offspring hippocampus

  • Toxicol Lett. 2019 Feb;301:114-124. doi: 10.1016/j.toxlet.2018.11.013.
Zhenmin Qiu 1 Yi Wang 1 Jie Chen 2
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, School of Public Heath, China Medical University, PR China.
  • 2 Department of Occupational and Environmental Health, School of Public Heath, China Medical University, PR China. Electronic address: Jchen@cmu.edu.cn.
Abstract

Nonylphenol (NP) is a persistent organic pollutant (POP) that has potential for neurotoxicity. The central nervous system (CNS) of fetus and child is highly sensitive to POPs, with environmental NP exposure, in particular, receiving increasing attention. Microglia (MG) are vital resident immune cells in CNS that defend against exogenous chemicals. This makes them a potentially target of NP. We sought to explore the effects of maternal exposure to NP during pregnancy and lactation on MG in the offspring hippocampus, the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by MG, and the associated underlying mechanisms. We found that maternal exposure to NP activated MG and increased the production of NO and PGE2 in the offspring hippocampus. Nuclear translocation of p65 was found to co-localize with hippocampal MG. Activation of TLR4/MyD88/NF-κB and Nrf2 signaling were observed in the offspring hippocampus. Interestingly, the inhibition of TLR4 signaling with CLI-095 partly inhibited NP-induced NO and PGE2 expression in BV2, a MG cell line. Together, our results suggested that maternal exposure to NP might increase the production of NO and PGE2 by over-activated MG in the offspring hippocampus. TLR4/MyD88/NF-κB and Nrf2 signaling pathways may be involved in the activation of MG and the increased production of NO and PGE2.

Keywords

Microglia; NF-κB signaling; Nitric oxide; Nonylphenol; Nrf2 signaling; Prostaglandin E2.

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