title: BMPR2 is required for postimplantation uterine function and pregnancy maintenance.
abstract: Abnormalities in cell-cell communication and growth factor signaling pathways can lead to defects in maternal-fetal interactions during pregnancy, including immunologic rejection of the fetal/placental unit. In this study, we discovered that bone morphogenetic protein receptor type 2 (BMPR2) is essential for postimplantation physiology and fertility. Despite normal implantation and early placental/fetal development, deletion of Bmpr2 in the uterine deciduae of mice triggered midgestation abnormalities in decidualization that resulted in abnormal vascular development, trophoblast defects, and a deficiency of uterine natural killer cells. Absence of BMPR2 signaling in the uterine decidua consequently suppressed IL-15, VEGF, angiopoietin, and corin signaling. Disruption of these pathways collectively lead to placental abruption, fetal demise, and female sterility, thereby placing BMPR2 at a central point in the regulation of several physiologic signaling pathways and events at the maternal-fetal interface. Since trophoblast invasion and uterine vascular modification are implicated in normal placentation and fetal growth in humans, our findings suggest that abnormalities in uterine BMPR2-mediated signaling pathways can have catastrophic consequences in women for the maintenance of pregnancy.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Li
authors.forename: Caterina
authors.initials: C
authors.lastname: Clementi
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: Martin M
authors.initials: MM
authors.lastname: Matzuk
mesh_terms: D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003656:Decidua / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010064:Embryo Implantation; D004958:Estradiol / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D015870:Gene Expression; D015726:Giant Cells / Q000473:pathology; D007247:Infertility, Female / Q000235:genetics; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000098:blood supply / Q000473:pathology; D011247:Pregnancy; D011255:Pregnancy Maintenance; D011374:Progesterone / Q000097:blood; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000473:pathology; D014599:Uterus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042682:Angiopoietins; D019409:Interleukin-15; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011374:Progesterone; D004958:Estradiol; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II; C485617:Corin protein, mouse; D012697:Serine Endopeptidases