BMPR2 is required for postimplantation uterine function and pregnancy maintenance
Takashi Nagashima, Qinglei Li, Caterina Clementi, John P. Lydon, Francesco J. DeMayo, Martin M. Matzuk
Takashi Nagashima, Qinglei Li, Caterina Clementi, John P. Lydon, Francesco J. DeMayo, Martin M. Matzuk
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Research Article Reproductive biology

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

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

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Figure 1

Decidual growth restriction, fetal growth retardation, and hemorrhagic implantation sites in pregnant Bmpr2 cKO female mice.

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Decidual growth restriction, fetal growth retardation, and hemorrhagic ...
(A) Hemorrhagic implantation sites in pregnant Bmpr2 cKO female mice. Scale bar: 1 cm. (B) Fetal growth retardation in Bmpr2 cKO female mice is grossly obvious at E10 and E11. Scale bar: 1 mm. (C) Uterine hemorrhage and discharge of fetus and placenta in Bmpr2 cKO female mice at E12. Scale bar: 1 cm (top); 5 mm (bottom). (D) Hemorrhagic implantation sites and fetal growth retardation were detected in Bmpr2 cKO female mice beginning at E9. All sections were stained with H#x00026;E. Higher-magnification images of the boxed regions are shown at right. Scale bar: 1 mm (lower magnification); 300 #x003bc;m (higher magnification).