Placental morphology at day 18.5 post coitum in the hsFLT1/rtTA mouse model. Placentas from the various experimental groups were collected and stained with hematoxylin and eosin (H&E). The following groups are shown either in 2× overview (left) or in a 20× detailed structure view of spongiotrophoblast (middle) and labyrinth (right): control [n = 16 (A–C)] and doxycycline (Dox) control placentas [n = 12 (D–F)], fetal growth restriction wild-type [FGR wt; n = 9 (G–I)], FGR heterozygous het; n = 3 (J–L) and FGR homozygous placentas [hom; n = 10 (M–O)]. High-expressing human soluble fms-like tyrosine kinase 1 (hsFLT1) FGR hom and FGR het placentas (maternal and placental hsFLT1 expression) exhibited enlarged blood-filled spaces (lacunas, indicated by gray arrows) within the entire placenta, but low-expressing hsFLT1 FGR wt placentas (with maternal hsFLT1 expression only), non-expressing hsFLT1 control placentas, and Dox control placentas did not exhibit such lacunas [(A,D) compared to (G,J,M)]. The lacunas were located not only in the spongiotrophoblast [(B,E) compared to (H,K,N)], but also in the labyrinth of hsFLT1–expressing placentas [(C,F) compared to (I,L,O)]. Interestingly, the FGR wt placentas exhibited a phenotype with a morphology between those of FGR hom/het placentas and control placentas, in which the labyrinth compartment is more densely characterized by an intense staining pattern. Scale bar 2× overview = 1,000 μm; 20× details = 100 μm. D, decidua; L, labyrinth; S, spongiotrophoblast; U, umbilical cord.