Maternal transfer of F-53B inhibited neurobehavior in zebrafish offspring larvae and potential mechanisms: Dopaminergic dysfunction, eye development defects and disrupted calcium homeostasis

F-53B 母体转移抑制斑马鱼后代幼虫的神经行为及其潜在机制:多巴胺能功能障碍、眼睛发育缺陷和钙稳态紊乱

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作者:Luyin Wu, Mohammed Zeeshan, Yao Dang, Yun-Ting Zhang, Li-Xia Liang, Jing-Wen Huang, Jia-Xin Zhou, Li-Hao Guo, Yuan-Yuan Fan, Ming-Kun Sun, Tao Yu, Yue Wen, Li-Zi Lin, Ru-Qing Liu, Guang-Hui Dong, Chu Chu

Abstract

Maternal exposure to environment toxicants is an important risk factor for neurobehavioral health in their offspring. In our study, we investigated the impact of maternal exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs, commercial name: F-53B) on behavioral changes and the potential mechanism in the offspring larvae of zebrafish. Adult zebrafish exposed to Cl-PFESAs (0, 0.2, 2, 20 and 200 μg/L) for 21 days were subsequently mated their embryos were cultured for 5 days. Higher concentrations of Cl-PFESAs in zebrafish embryos were observed, along with, reduced swimming speed and distance travelled in the offspring larvae. Molecular docking analysis revealed that Cl-PFESAs can form hydrogen bonds with brain-derived neurotropic factor (BDNF), protein kinase C, alpha, (PKCα), Ca2+-ATPase and Na, K - ATPase. Molecular and biochemical studies evidenced Cl-PFESAs induce dopaminergic dysfunction, eye developmental defects and disrupted Ca2+ homeostasis. Together, our results showed that maternal exposure to Cl-PFESAs lead to behavioral alteration in offspring mediated by disruption in Ca2+ homeostasis, dopaminergic dysfunction and eye developmental defects.

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