Placental explants were surgically placed under the kidney capsules of Scid mice and maintained for 1 (A, C, D, and F–H) or 3 weeks (B, E, and I) before histological analyses. (A) Villous cores (arrows) mark the original implantation sites. One week after implantation, cytotrophoblasts invaded murine renal tissue. (B) After 3 weeks the amount of cytotrophoblast-occupied renal parenchyma increased dramatically, extending well into the cortex, with select clusters migrating even deeper. Many kidney tubules within remained intact (arrow). (C) CD31 staining revealed, within areas of cytotrophoblast invasion, vascular networks (arrow) with very different morphology from resident renal vessels (compare inset with F). (D and E) Higher-magnification images of A and B show that the migration route of invasive cytotrophoblasts was restricted to the peritubular spaces. (F) CD31 and cytokeratin double staining revealed that cells were closely associated with blood vessels coursing through these areas. (G) Cells also breached these vessels, as demonstrated by platelet deposition (red), which occurred only in areas of cytotrophoblast invasion. (H) Cytotrophoblast expression of stage-specific antigens mimicked the pattern observed during human uterine invasion. (I) Nuclear volume increased, indicative of chromosome amplification associated with cytotrophoblast invasion (25), as illustrated by the relatively small nuclear diameter of progenitor cells (arrow; left inset) compared with that of invasive cells (arrowheads; right inset). Scale bars: 500 μm (A–C); 20 μm (C, inset); 50 μm (D–I); 5 μm (I, insets).