Loss of MT1-MMP and MT2-MMP leads to defective LA formation. (A) Cross section of H&E-stained normal placentas at E10.5 showing the AM and the placental LA with abundant FVs and MSs. Insets in (A) and (B) show entire placentas in cross section at low magnification. (B) Placenta from (1−/−; 2−/−) embryo displaying a more compact structure of the labyrinth with sparse FVs and MSs. (C) Area framed in panel A shown at high magnification. Note the abundant FVs with nucleated red cells and the adjacent MSs with enucleated red cells. (D) Area framed in panel B demonstrating the underdeveloped LA of (1−/−; 2−/−) placentas. FVs are sparse and penetrate only to a shallow depth. Top white frame is enlarged in right bottom corner and displays apoptotic bodies and dead cells surrounding the fetal vessel (arrowheads). (E-F) Same images as in panels C-D with FVs outlined in yellow. (G) Immunohistochemical localization of collagen type IV outlining FVs of the elaborately branched LA. (H) Collagen type IV–specific stain of placenta from (1−/−; 2−/−) littermate showing diminished vessel branching and penetration (asterisks) into the prospective LA. (I-J) H&E stains of sections serial with sections shown in panels G-H. Scale bars: (A-B) 200 μm; (A-B inset) 1 mm; (B-J) 100 μm.