1. Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation
- Author
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Chu Chu, Hao Ran, Yang Zhou, Kun Zhao, Yun-Ting Zhang, Yuan-Yuan Fan, Lu-Yin Wu, Li-Xia Liang, Jing-Wen Huang, Li-Hao Guo, Jia-Xin Zhou, Li-Zi Lin, Jun-Heng Ma, Chao-Fan Zhang, Yun-Jiang Yu, Guang-Hui Dong, and Xiao-Miao Zhao
- Subjects
Cl-PFESAs ,NLRP3 inflammasome ,Apoptosis ,Pyroptosis ,Reproductive toxicity ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5–14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.
- Published
- 2024
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