Bisphenol S Induces Ectopic Angiogenesis in Embryos via VEGFR2 Signaling, Leading to Lipid Deposition in Blood Vessels of Larval Zebrafish.

Bisphenol S (BPS), used as a bisphenol A substitute, has been detected in various environments. However, the safety of BPS is still unclear. Here, zebrafish embryos were exposed to BPS (0, 1, 10, and 100 μg/L) for 24, 48, 72, 96 h, and 15 days. BPS induced ectopic sprouting of budding blood vessels in embryos, but the blood flow velocity within these lesions was unchanged at 48 h. At 72 h postfertilization (hpf), by observing the subintestinal venous plexus responsible for yolk absorption, we found that VEGFR2 transduced an angiogenic signal and that the subsequent reduction in blood flow velocity inhibited yolk absorption. At 96 hpf, yolk consumption was still delayed because of the disturbed transportation route, resulting in transient extensive lipid retention in the blood vessels. After feeding, obvious atherogenic lipids were discovered in the blood vessels, especially in bends, bifurcations, and stenoses. This dynamic visualization of the pathogenesis demonstrates a plausible mechanistic link between BPS exposure-induced embryonic vessel overgrowth and an increased atherosclerosis risk.