Exposure to perfluorooctanoic acid (PFOA) decreases neutrophil migration response to injury in zebrafish embryos

Abstract

Objective Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant and a known immune suppressant in humans and experimental animal models. Studies on PFOA have focused on suppression of the adaptive immune response; however, little is known of the impact on innate immunity, especially during embryogenesis. Therefore, we utilized the zebrafish chemotaxis assay coupled with in situ hybridization for myeloperoxidase expression to determine the effects of PFOA exposure on neutrophil migration in the developing zebrafish embryo. Zebrafish embryos are a well-established in vivo model that exhibit high homology with the development of human innate immunity. Results Treatment of zebrafish with increasing concentrations of PFOA identified the lethal concentration in 50% of the embryos (LC 50 ) to be 300 mg/L. Utilizing the zebrafish chemotaxis assay, this study showed that wounding induced significant neutrophil migration to the site of injury, and that neutrophil number in the wound region was significantly reduced in response to 48-h PFOA exposure (well below doses causing acute mortality). This study demonstrates that the developing embryo is sensitive to PFOA exposure and that PFOA can modify the innate immune system during embryonic development. These results lay the groundwork for future investigation on the mechanisms underlying PFOA-induced developmental immunotoxicity.

Perfluorooctanoic acid exposure and its neurodegenerative consequences

“…This statistical difference was seen in all of the PFOA groups as well as the carriers. The PFOA (10) group was considerably different from the other groups in terms of females. Furthermore, there were substantial differences between the PFOA (1) group and DEXA.…”

“…This staining revealed a decrease in myelin density in males at high concentrations. The PFOA (10) and PFOA (20) groups are considerably lower than the vehicle group, but the other groups did not differ signi cantly as compared with the control group. There was a signi cant difference in the dose of 20 mg/kg/day compared to the groups of 1, 5 mg/kg/day, and DEXA in the analyzed groups.…”

“…In the SVZ region, males labeled with the BrdU PFOA group (20) displayed noteworthy differences with PFOA (1), DEXA, and the Vehicle groups. While the PFOA (5) and PFOA (10) groups were signi cantly different only from the Vehicle and DEXA groups.…”

“…With higher dosages of PFOA, a decrease in neurogenesis was found in the cells of the male corpus callosum, which were marked with BrdU in the same way as females. The PFOA (1) group differed considerably from the PFOA (20), PFOA (10), and PFOA (5) groups, while the PFOA (5) group differed only from the Vehicle group; the PFOA (20) and PFOA (10) groups differed signi cantly from the Vehicle and DEXA groups. Between the other groups, there was no statistically signi cant difference.…”

“…Exposure to PFOA lowered the number of CD4+ and CD8+ lymphocytes in brain tissue. After counting CD8+ cells in females, the PFOA (1) group showed a signi cant difference with PFOA (10), PFOA (20), and DEXA groups, but not from the Vehicle group or the PFOA (5) group. The PFOA (5) group differed signi cantly from the PFOA (10), PFOA (20), and DEXA groups.…”