Figure 6.

Analysis of fetal (left) and maternal (right) vascularization in the placental labyrinth in the hsFLT1/rtTA mouse model. Immunohistochemical staining of Cd31 (brown staining) in the labyrinth area indicates fewer fetal vessels (indicated by gray arrows) and inadequate formation of blood spaces (indicated by black asterisks) in high-expressing human soluble fms-like tyrosine kinase 1 (hsFLT1) fetal growth restriction homozygous (FGR hom; n = 10) (I) and FGR heterozygous (het; n = 3) (G) placentas (maternal and fetal hsFLT1 expression) than in low-expressing hsFLT1 FGR wt [n = 9 (E)] (maternal expression only) and non-expressing hsFLT1 control (n = 16) and doxycycline (Dox) control (n = 12) placentas (A,C). For Cd31 staining nuclei are counterstained in blue. Cells lining dilated vessels (lacunas) in high-expressing hsFLT1 FGR hom [n = 10 (J)] and FGR het [n = 3 (H)] placentas exhibited placental alkaline phosphatase (PLAP) activity (dark purple staining), a finding indicating the presence of sinusoidal trophoblast giant cells (S-TGCs); therefore, these vessels are characterized as maternal sinusoids (indicated by gray arrowheads). In addition, PLAP-positive vessels in low-expressing hsFLT1 FGR wt placentas [n = 9 (F)] exhibited a different phenotype, especially for the maternal sinusoids, with more longitudinally arranged and slightly larger sinusoids than in the other groups (indicated by white asterisks). In contrast, the controls [control n = 16 (B) and Dox control n = 12 (D)] did not exhibit dilatation of maternal sinusoids. For PLAP staining nuclei are counterstained in light red. Scale bar 20× details = 100 μm and 40× details = 50 μm.