Bisphenol-A alters hematopoiesis through EGFR/ERK signaling to induce myeloblastic condition in zebrafish model

Experimental evidence from the etiology of cancer studies suggests that a correlation between Bisphenol-A (BPA) exposure and alterations in hematopoiesis leads to blood cancer. In our study zebrafish were used to assess the lethality, developmental effect, embryonic apoptosis and changes in transcription factor of hematopoiesis through EGFR/ERK signaling pathways in response to BPA. The in silico interaction of EGFR and BPA was analysed by molecular dynamic simulation. According to our results, BPA induced a significant lethal effect in hatching retardation, reduction in heart rate and teratogenic effects on zebrafish embryos and larvae at three different concentrations 100, 500 and 2500 mu g/L. The mortality of adult zebrafish exposed to the acute toxicity of BPA from 5 to 30 mg/L concentrations was determined for 96 h. The peripheral blood cells and vital organs such as kidney, liver and spleen from BPA exposed fish showed predominantly abnormal myeloid blast cells along with severe morphological changes in erythrocytes at sublethal concentration 245 mu g/L. The BPA showed the highest binding affinity to zebrafish EGFR with a docking score of -7.5 kcal/mol with an RMSD of 3.0 nm during MD simulation. We found that EGFR/ERK overexpression leads to induce hematopoietic cell proliferation and impaired differentiation, which enhances the myeloid repopulating activity and the accumulation of immature myeloblast cells. BPA also caused a corresponding increase in expression of hematopoietic transcription factor c-MYB and

Automated summary

The experimental study demonstrated a correlation between BPA exposure and alterations in hematopoiesis that can lead to blood cancer. Zebrafish exposed to BPA showed lethality, developmental effects, embryonic apoptosis, and changes in transcription factors related to hematopoiesis. Molecular dynamic simulation suggested a strong binding affinity between BPA and zebrafish EGFR, indicating potential mechanisms for BPA-induced effects on hematopoietic cells.