Prostaglandin E2 promotes embryonic vascular development and maturation in zebrafish

Abstract

Prostaglandin (PG)-E2 is essential for growth and development of vertebrates. PGE2 binds to G-coupled receptors to regulate embryonic stem cells differentiation and maintains tissue homeostasis. Overproduction of PGE2 by breast tumor cells promotes aggressive breast cancer phenotypes and tumor-associated lymphangiogenesis. In this study, we investigated novel roles of PGE2 in early embryonic vascular development and maturation with microinjection of PGE2 in fertilized zebrafish (Danio rerio) eggs. We injected Texas red-dextran to trace vascular development. Embryos injected with the solvent of PGE2 served as vehicle. Distinct developmental changes were noted from 28-96 hours post fertilization (hpf), showing an increase in embryonic tail-flicks, pigmentation, growth, hatching, and larval movement post-hatching in the PGE2-injected group compared to the vehicle. We recorded a significant increase in trunk vascular fluorescence and maturation of vascular anatomy; embryo heartbeat and blood vessel formation in the PGE2 injected group. At 96hpf, all larvae were sacrificed to measure vascular marker mRNA expression. We observed a significant increase in the expression of stem cell markers efnb2a, ephb4a; angiogenesis markers vegfa, kdrl, etv2 and lymphangiogenesis marker prox1 in the PGE2-group compared to the vehicle. This study shows the novel roles of PGE2 in promoting embryonic vascular maturation and angiogenesis in zebrafish.