Fig. 4. Defective placental labyrinth development in Cdx2^+/-/Cdx4^-/0 compound mutant embryos. (A-H) Hematoxylin and Eosin-stained sections of placentas from wild-type (A,C,E,G; C is an enlargement of A; G is an enlargement of E) and Cdx2^+/-/Cdx4^-/0 compound mutant littermates (B,D,F,H; D is an enlargement of B; H is an enlargement of F). (A-D) At E9.5, only some Cdx2^+/-/Cdx4^-/0 allantoic vessels have started to penetrate the chorionic trophoblast layer without overt signs of branching morphogenesis, whereas wild-type placentas show branched vessels deeply penetrating the chorionic ectoderm. These vessels intermingle with maternal blood sinuses, from which they are separated in many places by only a thin haemotrichorial membrane (triangle in C) in the crucial part of the labyrinth (la in A) that is concerned with the vital interchanges between maternal and fetal circulation. (E-H) At E10.5, the defect becomes more severe, as revealed by the complete separation of maternal and embryonic blood flows (mrb and frb in H) and the virtual absence of the labyrinth (F, compare with E). Scale bars: 100 µm. cp, chorionic plate; mrb, maternal red blood cell; frb, fetal red blood cell; la, labyrinthine trophoblast.