BMPR2 is required for postimplantation uterine function and pregnancy maintenance
Open Access
- 8 May 2013
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 123 (6), 2539-2550
- https://doi.org/10.1172/jci65710
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.Keywords
This publication has 62 references indexed in Scilit:
- Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancyNature, 2012
- Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisionsProceedings of the National Academy of Sciences of the United States of America, 2011
- Death effector domain–containing protein (DEDD) is required for uterine decidualization during early pregnancy in miceJCI Insight, 2011
- Endocannabinoid signaling directs differentiation of trophoblast cell lineages and placentationProceedings of the National Academy of Sciences of the United States of America, 2010
- Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in miceJCI Insight, 2010
- An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxiaNucleic Acids Research, 2009
- Maternal hypoxia activates endovascular trophoblast cell invasionDevelopmental Biology, 2008
- Bmp2 Is Critical for the Murine Uterine Decidual ResponseMolecular and Cellular Biology, 2007
- Generation of a floxed allele of the mouse BMP type II receptor genegenesis, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001