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
Takashi Nagashima, Qinglei Li, Caterina Clementi, John P. Lydon, Francesco J. DeMayo, Martin M. Matzuk
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