title: Type 1 and 3 inositol trisphosphate receptors are required for extra-embryonic vascular development.
abstract: The embryonic-maternal interface of the placental labyrinth, allantois, and yolk sac are vital during embryogenesis; however, the precise mechanism underlying the vascularization of these structures remains unknown. Herein we focus on the role of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular Ca(2+) release channels, in placentation. Double knockout (DKO) of type 1 and 3 IP3Rs (IP3R1 and IP3R3, respectively) in mice resulted in embryonic lethality around embryonic day (E) 11.5. Because IP3R1 and IP3R3 were co-expressed in endothelial cells in the labyrinth, allantois, and yolk sac, we investigated extra-embryonic vascular development in IP3R1- and IP3R3-DKO mice. The formation of chorionic plates and yolk sac vessels seemed dysregulated around the timing of the chorio-allantoic attachment, immediately followed by the disorganization of allantoic vessels, the decreased expression of the spongiotrophoblast cell marker Tpbpa and the growth retardation of the embryos in DKO mice. Fluorescent immunohistochemistry demonstrated downregulation of a vascular endothelial marker, CD31, in labyrinth embryonic vessels and poor elongation of extra-embryonic mesoderm into the labyrinth layer in DKO placenta, whereas the branching of the DKO chorionic trophoblast was initiated. In addition, allantoic and yolk sac vessels in extra-embryonic tissues were less remodeled in DKO mice. In vitro endothelial cord formation and migration activities of cultured vascular endothelial cells derived from human umbilical vein were downregulated under the inhibition of IP3R. Our results suggest that IP3R1 and IP3R3 are required for extra-embryonic vascularization in the placenta, allantois, and yolk sac. This is the first demonstration of the essential role of IP3/IP3Rs signaling in the development of the vasculature at the embryonic-maternal interface.
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan; Health Center, Keio University, Kanagawa, Japan.
authors: Keiko
authors: K
authors: Uchida
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Maki
authors: M
authors: Nakazawa
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Chihiro
authors: C
authors: Yamagishi
authors: Laboratory for Developmental Neurobiology, Developmental Brain Science Group, Brain Science Institute, RIKEN, Saitama, Japan.
authors: Katsuhiko
authors: K
authors: Mikoshiba
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Yamagishi
mesh_terms: D000482:Allantois / Q000098:blood supply* / Q000196:embryology; D000818:Animals; D002460:Cell Line; D047108:Embryonic Development; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010920:Placenta / Q000098:blood supply* / Q000196:embryology; D010929:Placentation / Q000235:genetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology / Q000196:embryology*; D015017:Yolk Sac / Q000098:blood supply* / Q000196:embryology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Allantois; Angiogenesis; Embryonic vessels; Intracellular calcium signaling; Placental labyrinth; Yolk sac