Silver nanocolloid affects hindbrain vascular formation during medaka embryogenesis

Abstract

Angiogenesis is essential for the normal development of an embryo. Silver nanocolloid (SNC) is known to induce vascular malformation in the medaka embryo. We focused on the development of the central arteries (CtAs) in the hindbrain of Japanese medaka. The CtAs and the basilar artery from which they branch are essential for transporting the blood and nutrients necessary to support the hindbrain parenchyma and the development of the pons and cerebellum from the hindbrain. We exposed medaka embryos at developmental stage 21 (6 somite stage), to 0, 0.5, 5, or 10 mg/L SNC and evaluated hatching rate, number of thrombi per embryo, head size (length and width), body length, and angiogenesis. Although all SNC‐exposed embryos hatched, their head size and body length were small in comparison to controls; in addition, the number of thrombi in the head increased and head size and body length decreased as the SNC concentration increased. To evaluate vasculogenic abnormalities, we performed whole‐mount in situ hybridization using a vascular marker (eg, fl7) and visualized the CtAs in medaka embryos. In control embryos, CtAs started to sprout at stage 32 (somite completion stage) and their extension was complete by stage 35 (pectoral fin blood circulation stage). In contrast, CtAs failed to sprout in SNC‐exposed embryos, and thrombi were present. Furthermore, qRT‐PCR analysis showed that SNC significantly suppressed the egfl7 expression level at stage 35. Together, our findings suggest that SNC induced decreased developments of head and body in medaka embryos due to insufficient angiogenesis and hindbrain vascular formation.

Transition metals in angiogenesis – A narrative review

“…It appears silver, in particular silver NPs, have an inhibitory effect on angiogenesis. These findings were confirmed in multiple studies discussed, presenting substantial in vivo evidence [ [239] , [240] , [241] , [242] , 244 ]. Nevertheless, the in vivo proangiogenic findings should not be overlooked [ 246 ] ( Table 1 and Fig.…”

“…Further research investigating molecular mechanisms found silver NPs to inhibit HIF1-α and VEGFR, as well as their proangiogenic target genes [ 240 , 243 ]. In an experiment conducted on medaka fish embryogenesis, the previous antiangiogenic results were corroborated [ 244 ]. Specifically, silver nano-colloid (SNC) was applied to the embryos using epidermal growth factor-like domain 7 (EGFL7) to evaluate angiogenesis.…”

“…1 ). Indeed, the treatment with SNC led to vascular malformation and EGFL7 levels being decreased [ 244 ].…”

Silver Ion Decreases Foreign Body Reaction and Venous Neointimal Hyperplasia through the Inhibition of Interleukin-33 Expression

“…We showed that silver can decrease IL-33 expression not only in subcutaneous and abdominal cavity implantation but also in venous patch venoplasty. In humans and mice, IL-33 is mainly produced by endothelial cells, epithelial cells, fibroblast-like cells, and myofibroblasts; IL-33 expression in murine endothelial cells can be induced during inflammation [39]. In this study, decreased IL-33 expression was observed in the silver hydrogel group, partly because silver can inhibit inflammation after patch angioplasty.…”

“…In this study, decreased IL-33 expression was observed in the silver hydrogel group, partly because silver can inhibit inflammation after patch angioplasty. In Japanese medaka, silver can induce insufficient angiogenesis and hindbrain vascular formation [40]. Other studies have shown that silver nanoparticles conjugated with heparin derivative possess antiangiogenic properties [41].…”