Fig. 4. Bleeding and giant trophoblast fragility in K18^–/–K19^–/– mice (A and B) Sagittally sectioned wild-type and doubly deficient E9.5 embryos. (A) In the wild-type embryos the barrier between embryonic and maternal compartments is formed by giant trophoblast (gT) cells (arrows). The visceral yolk sac (VYS), placenta (P) and amnion (A) are clearly visible. (B) Note the haematoma (H) in the mutant embryo, which is deforming the parietal and visceral yolk sacs. In the region with the haematoma, trophoblast giant cells surrounding the conceptus (arrows) were destroyed by cytolysis. Bar, 500 µm. (C) Higher magnification of (B). The layer of trophoblast giant cells is disrupted, with trophoblast giant cells in the process of cytolysis (arrows). Cytolysed trophoblast giant cells were surrounded by granulocytes. The origin of blood was a maternal vessel in the decidual tissue (Dcv). After breakdown of the trophoblast giant cell layer, maternal blood entered between the parietal yolk sac (PYS) and decidual tissue (Dc) unimpaired. The haematoma consisted of maternally derived erythrocytes, fibrin (Fi) and infiltrated granulocytes. Note that Reichert’s membrane (basal lamina in PYS) was not penetrated by blood. Em, embryo; ∗, visceral yolk sac. Bar, 200 µm.