Fig. 4. Abnormal vascularization of Map2k1^-/- placental labyrinth. The embryonic vascular network of E10.5 wild-type (A) and Map2k1^-/- (B) placentas was revealed by anti-CD31 staining (black arrows). In Map2k1^-/- placentas, the fetal blood vessels were restricted at the chorioallantoic plate (B). Detection of p38 MAPK activation in wild-type (C) and Map2k1^-/- (D) placentas revealed a high activation of p38 MAPK in the embryonic blood vessels of the labyrinth of wild-type specimens and at the chorioallantoic interface of Map2k1^-/- placentas (black arrowheads). Vegf expression in wild-type (E) and Map2k1^-/- (F) placentas was analyzed by in situ hybridization (red signal and blue arrows). High Vegf expression levels were detected in the allantoic region of Map2k1^-/- placentas, indicating a response to hypoxic stress. For placental structure identification, near adjacent Hematoxylin and Eosin-stained sections of specimens E and F are presented in Fig. 1A. X-Gal staining of Map2k1^+/- (G) and Map2k1^-/- (H) placentas was used to define the Map2k1 expression profile in normal and mutant placentas. The labyrinthine region is presented. In Mapk2k1^-/- specimens, X-Gal staining is restricted to the chorioallantoic plate. al, allantois; ch, chorionic plate; d, deciduum; g, tropohoblast giant cells; l, labyrinth. Scale bars: 50 µm in A-D,G,H; 100 µm in E,F.