Abnormalities in cell-cell communication and growth factor signaling pathways canlead to defects in maternal-fetal interactions during pregnancy, includingimmunologic rejection of the fetal/placental unit. In this study, we discovered thatbone morphogenetic protein receptor type 2 (BMPR2) is essential for postimplantationphysiology and fertility. Despite normal implantation and early placental/fetaldevelopment, deletion of Bmpr2 in the uterine deciduae of micetriggered midgestation abnormalities in decidualization that resulted in abnormalvascular development, trophoblast defects, and a deficiency of uterine natural killercells. Absence of BMPR2 signaling in the uterine decidua consequently suppressedIL-15, VEGF, angiopoietin, and corin signaling. Disruption of these pathwayscollectively lead to placental abruption, fetal demise, and female sterility, therebyplacing BMPR2 at a central point in the regulation of several physiologic signalingpathways and events at the maternal-fetal interface. Since trophoblast invasion anduterine vascular modification are implicated in normal placentation and fetal growthin humans, our findings suggest that abnormalities in uterine BMPR2-mediatedsignaling pathways can have catastrophic consequences in women for the maintenance ofpregnancy.
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