Bisphenol E Neurotoxicity in Zebrafish Larvae: Effects and Underlying Mechanisms

Area of Science:

• Environmental Toxicology
• Neuroscience
• Molecular Biology

Background:

• Endocrine-disrupting chemicals (EDCs) like bisphenol E (BPE) are global environmental health concerns.
• BPE, a bisphenol A substitute, is prevalent in environmental matrices and known for developmental/reproductive toxicity.
• Potential neurotoxic risks of BPE are suggested but mechanisms remain unclear.

Purpose of the Study:

• To predict potential toxic mechanisms and molecular targets of BPE using network toxicology and molecular docking.
• To investigate the neurotoxic effects and underlying mechanisms of BPE in zebrafish larvae.
• To evaluate the ecological risks and inform environmental management strategies for BPE.

Main Methods:

• Zebrafish model utilized for predicting BPE's toxic mechanisms and action targets via network toxicology and molecular docking.
• RT-qPCR employed to assess neurotoxic effects and gene expression related to neurodevelopment, synaptic signaling, and apoptosis.
• Analysis of embryonic spontaneous movements, larval body length, neuronal fluorescence, and axon length.

Main Results:

• BPE exposure significantly decreased embryonic movement frequency and larval body length in zebrafish.
• Reduced neuronal fluorescence and shortened axon length were observed, indicating neurodevelopmental disruption.
• HSP90AB1 identified as a core target; cGMP/PKG signaling pathway identified as the primary neurotoxic route.

Conclusions:

• BPE induces neurotoxicity in zebrafish larvae by inhibiting the cGMP/PKG pathway, leading to neuronal apoptosis and disrupted neurodevelopment.
• Suppressed larval motor behavior is a consequence of BPE-induced neurotoxicity.
• Findings provide crucial evidence for understanding BPE's neurodevelopmental toxicity and assessing its ecological risks.