BMPR2 is required for postimplantation uterine function and pregnancy maintenance
Takashi Nagashima, … , Francesco J. DeMayo, Martin M. Matzuk
Takashi Nagashima, … , Francesco J. DeMayo, Martin M. Matzuk
Published June 3, 2013; First published May 8, 2013
Citation Information: J Clin Invest. 2013;123(6):2539-2550. https://doi.org/10.1172/JCI65710.
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Categories: 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).