MRI analysis of angiogenesis during mouse embryo implantation

Uterine receptivity and embryo implantation depend on local induction of angiogenesis and vascular permeability. Poor uterine receptivity has been implicated in implantation failure; however, relatively little is known about the mechanism that underlies endometrial vascular hyperpermeability in implantation sites. Here we show that contrast-enhanced (CE)-MRI and fluorescence microscopy using biotin-BSA-GdDTPA allowed high-resolution detection and quantitative assessment of mouse embryo implantation sites as early as embryonic day 4.5 (E4.5), and subsequent vascular expansion at E5.5. Vessel permeability, but not blood volume, was significantly elevated in E4.5 implantation sites relative to nonimplanted uterus, showing that elevation of vascular permeability is a very early response preceding E4.5. A significantly increased blood volume was detected by MRI and fluorescence microscopy in implantation sites between E4.5 and E5.5. On the other hand, despite the increase in blood volume, implantation sites showed only a small nonsignificant further increase in vascular permeability during these 2 days, demonstrating the rapid dynamics of vascular remodeling during the early days of pregnancy. Functional imaging by MRI, as reported here, allows multiparametric measurement of angiogenesis during normal mouse implantation and would facilitate the application of MRI to evaluate involvement of the vasculature in mouse models of impaired implantation.