Bisphenol-A diminishes neutrophil recruitment in zebrafish

Abstract

The prevalent use of bisphenol-A (BPA) in food containers, thermal paper, and other products provides an environmental challenge to the immune system of both humans and wildlife as BPA disrupts estrogen activity and alters signaling. We are exploring the impact of in vivo BPA exposure on innate immunity in both mice and zebrafish. Our earlier work in C57BL/6J mice showed that low dose, in vivo BPA exposure significantly decreases LPS-induced expression of CXCL-1, a chemokine that recruits neutrophils to the site of infection and the mouse homolog of human IL-8, in spleen cells. To determine if reduced chemokine secretion has a functional outcome, we expanded our studies to the zebrafish embryo model. Real time PCR analysis indicates that 4 to 6 day post fertilization (dpf) zebrafish exposed to environmentally relevant doses of BPA show reduced background expression of CXCL-8, the zebrafish homolog of mouse CXCL-1, and a reduction in the total number of neutrophils (4 dpf). BPA exposure also reduces the upregulation of CXCL-8 induced by a tail cut injury in 4 dpf zebrafish. MPO::GFP zebrafish expressing GFP under a neutrophil-specific myeloperoxidase promoter were used to track neutrophil movement for six hours following a tail cut injury. 4 dpf zebrafish exposed to BPA show a significantly reduced neutrophil recruitment to the site of injury compared to controls (p=0.004), a finding which correlates with the reduction in injury-induced CXCL-8 expression. Together our findings demonstrate that BPA exposure during early zebrafish development diminishes two key innate immune responses, thus potentially increasing susceptibility to infection.

Bisphenol A, bisphenol S and their glucuronidated metabolites modulate glycolysis and functional responses of human neutrophils

“…The reduction of CXCL8/IL-8 reserves and the delayed metabolic response to fMLP stimulation could impair neutrophil recruitment and early response to infection. Indeed, the chemotactic capacity of human neutrophils to fMLP was reduced after BPA exposure (Balistrieri et al, 2018) while zebrafish (Danio rerio) neutrophils exposed to BPA displayed lesser recruitment to the site of injury (Carson et al, 2018), highlighting the importance to consider in vivo exposure to bisphenols. Still, individuals are regularly exposed to a mixture of different bisphenol analogs in their environment that are then found in their blood, along with their metabolites.…”