Histopathologic analysis of C57/Bl6 neonatal mice treated for 5 days with G6-23-IgG, mFlt(1-3)-IgG, or control IgG. (A) Assessed vascular density in liver, heart, and kidney. Representative sections stained with rat anti–mouse VEGFR-2 antibody from each treatment group are illustrated. Vessel density was reduced to a similar extent by mFlt(1-3)-IgG and G6-23-IgG in all organs (see Table 2 for quantitative assessment). (B) Delayed and abnormal glomerular maturation in anti-VEGF–treated kidneys. Control glomeruli (iv) all have identifiable capillary loops supported by mesangial cells. Anti-VEGF treatment results in delayed glomerular maturation; persistent nephrogenic precursors including ureteric tubules and glomerular precursors are indicated with arrowheads (ii, iii, v, vi). Maturation appears more delayed in mFlt(1-3)-IgG– than G6-23-IgG–treated animals. Abnormal glomerular “rosettes” (ii, iii, v; arrows) are composed of podocytes surrounding largely avascular mesangial cores. (C) Alterations in the cartilaginous growth plate of anti-VEGF–treated animals. G6-23-IgG and mFlt(1-3)-IgG treatment results in expansion of proliferating chondrocytes (asterisks; compare control subpanel i with panels iv and vii). Subpanels ii, v, and viii show details of the proliferating chondrocyte zone, illustrating expansion of the lacunae of individual cells. Width of hypertrophic chondrocyte zone (arrowheads) is reduced in anti-VEGF–treated animals.