Hemorrhage in Nfe2^−/− mice occurs in utero. (A) P1 Nfe2^+/+ and Nfe2^−/− pups born by natural delivery. Yellow arrows point to representative head and body bleeds seen in the Nfe2^−/− mice (Nfe2^+/+, n = 8; Nfe2^−/−, n = 13). Scale bars, 1 mm. (B) P0 Nfe2^+/+ and Nfe2^−/− dissected brains. Yellow arrows point to bleeds in both frontal lobes. Scale bars, 1 mm. (C) E18.5 Nfe2^+/+ and Nfe2^−/− mice delivered by caesarean section. Yellow arrows point to bleeds. Scale bars, 1 mm. (D) E18.5 Nfe2^+/+ and Nfe2^−/− dissected brains. Yellow arrows point to frontal and ventricle bleeds in the Nfe2^−/− pups. Scale bars, 1 mm. (Ei-ii) Tables comparing the percentage of bleeds between E18.5 Nfe2^+/+ pups (Nfe2^+/+ n = 10, Nfe2^−/− n = 10) and P0 Nfe2^−/− pups (Nfe2^+/+ n = 8, Nfe2^−/− n = 13). (F-G) Histologic analysis demonstrates multiple bleed types present in the E18.5 Nfe2^−/− dissected brains, but not in the Nfe2^+/+ brain. Representative bleeds are shown in the cerebral cortex along with periventricular and intraventricular bleeds. Scale bars, 500 µm (F); 100 µm (G). (H) Nissl staining of E18.5 Nfe2^−/− (n = 3) coronal brain section and the corresponding region in the Nfe2^+/+ brain (n = 3). Scale bar, 500 µm (inset, 200 µm).