Genetic Evidence for Estrogenic Effects of Benzophenone-2 on Zebrafish Neurodevelopment and Its Signaling Mechanism

Environmental Science & Technology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 23, 2024

Estrogens play a crucial role in regulating various biological responses during the early stages of neurodevelopment. Benzophenone-2 (BP2), widely used organic ultraviolet (UV) filter, has been proven as an estrogenic compound, whereas effects BP2 on neurodevelopment remain largely unknown. Here, we investigated neurodevelopmental toxicity by exposing zebrafish embryos from 2 to 120 h postfertilization (hpf) at environmentally relevant concentrations. We demonstrated that life exposure induced multiple concentration-dependent impairments nervous system, including hypoactivity, abnormal brain morphology, impaired neurocyte proliferation, shortened axon, and increased apoptosis. Moreover, metabolomic profiling revealed decrease dopamine (DA) its metabolites BP2-treated larvae. Using E2 treatment morpholino knockdown assays, provided strong genetic evidence BP2-induced behavioral disorders were associated with estrogen-dependent signaling, especially estrogen receptors 2a 2b (esr2). Subsequently, transcriptomic indicated activation esr2 further inhibited expression LIM homeobox transcription factor 1 β (lmx1ba), which is vital for normal Consistently, overexpression lmx1ba inhibition obviously alleviated BP2-caused neurotoxicity, uncovering seminal toxicity. Our findings provide first fish can induce deficits dysfunction offer novel insights into mechanisms well other emerging benzophenones.

Язык: Английский

Oncogene-Induced Senescence Mitochondrial Metabolism and Bioenergetics Drive the Secretory Phenotype: Further Characterization and Comparison with Other Senescence-Inducing Stimuli

Опубликована: Янв. 1, 2024

Язык: Английский