Transient reduction of placental angiogenesis in PAI-1-deficient mice.
Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and fetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 days postcoitum (dpc). Knowing the key contribution of PAI-1 in the regulation of angiogenesis, we have now analyzed the consequence of PAI-1 deficiency on murine placentation. Morphological and quantitative computer-assisted image analysis revealed abnormal placental morphology in PAI-1-/- mice at 10.5 and 12.5 dpc. At 10.5 dpc, the genetic ablation of PAI-1 resulted in a transient reduction of both maternal and fetal vascularizations in the placenta and increased trophoblast cell density. This was associated with a poorer development of the labyrinth and an extension of the decidua. A larger spongiotrophoblast layer appeared at 12.5 dpc in PAI-1-deficient mice. Placental morphology was normalized at 14.5 dpc. Microarray analyses performed on laser capture microdissected labyrinths revealed that 46 genes were differentially expressed between the two genotypes at 10.5 dpc. However, only 11 genes were still differently modulated at 14.5 dpc, when normalization of placental morphology had taken place. This transcriptomic profiling highlighted a dysregulation in the expression of placenta-related cathepsin family members. Altogether our data provide evidence for a transient impaired placental morphology in PAI-1-deficient mice that is then normalized, leading to normal embryonic development.
Laboratory of Tumour and Development Biology, University of Liège, Tour de Pathologie (B23), Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA Cancer), Liège, Belgium.
Soraya
S
Labied
Silvia
S
Blacher
Peter
P
Carmeliet
Agnès
A
Noël
Francis
F
Frankenne
Jean-Michel
JM
Foidart
Carine
C
Munaut
D000818:Animals; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018919:Neovascularization, Physiologic; D010641:Phenotype; D010920:Placenta / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058258:Serpin E2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D058258:Serpin E2; C511869:Serpine2 protein, mouse