Egfl7 regulates embryonic angiogenesis and placental vascular function in mice

Epidermal growth factor-like domain 7 (Egfl7) is a secreted protein expressed in endothelial cells and plays an important role in angiogenesis and vascular stabilization. Previous studies have suggested an association between Egfl7 deficiency and vascular abnormalities; however, the specific functional roles of Egfl7 during the early stages of angiogenesis in embryonic development have not been fully elucidated. Therefore, in this study, we systematically investigated the functional role of Egfl7 during embryonic development using an Egfl7 knockout (KO) mouse model. Analysis of the embryonic model revealed that Egfl7 KO embryos exhibited increased partial lethality and growth retardation. These developmental abnormalities were accompanied by a marked reduction in placental vascular formation and decreased expression of the fatty acid transport proteins (Fatp4, Fatp6, and Fabp3), indicating impaired placental nutrient transfer function. Furthermore, reduced expression of Vegfr1 and Vegfr2 in the placenta, together with consistent downregulation of angiogenesis-related genes, was observed, suggesting that Egfl7 regulates multiple stages of angiogenesis, including vascular stabilization, sprouting, and branching. In addition, morphological abnormalities observed in the heart demonstrated that Egfl7 deficiency affects overall cardiovascular development beyond placental vascular defects. Taken together, these findings clearly demonstrate that Egfl7 is an essential regulatory factor for the initiation and maintenance of angiogenesis during physiological embryonic development, and suggest that modulation of Egfl7-mediated pathways may represent a potential therapeutic strategy for diseases associated with abnormal vascular growth.