Role of EFNB2/EPHB4 signaling in spiral artery development during pregnancy: An appraisal

EFNB2 and EPHB4, which belong to a large tyrosine kinase receptor superfamily, are molecular markers of arterial and venous blood vessels, respectively. EFNB2/EPHB4 signaling plays an important role in physiological and pathological angiogenesis, and its role in tumor vessel development has been extensively studied. Pregnancy and tumors share similar features, including continuous cell proliferation and increased demand for a blood supply. Our previous studies showed that Efnb2 and Ephb4 were expressed dynamically in the spiral arteries, uterine natural killer cells, and trophoblasts during mouse gestation Days 6.5-12.5. Moreover, uterine natural killer cells and trophoblasts are required for the modification of spiral arteries. Oxygen tension within the pregnant uterus, which contributes to the vascular development, also affects EFNB2 and EPHB4 expression. Considering the role of EFNB2/EPHB4 signaling in embryonic and tumor vascular development, and its dynamic expression in the decidua and placenta, we hypothesize that EFNB2 and EPHB4 are involved in the regulation of spiral artery remodeling. Investigating this hypothesis will help clarify the mechanisms of pathological pregnancy that may underlie abnormal spiral artery development.