BMPR2 is required for postimplantation uterine function and pregnancy maintenance
BMPR2 is required for postimplantation uterine function and pregnancy maintenance
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DOI：
10.1172/jci65710
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发表时间：
2013-06-01
影响因子：
15.9
通讯作者：
Matzuk, Martin M.
中科院分区：
文献类型：
--
作者：
Nagashima, Takashi;Li, Qinglei;Matzuk, Martin M.
细胞间通讯和生长因子信号通路的异常可导致妊娠期间母胎相互作用的缺陷，包括胎儿/胎盘单位的免疫排斥。在这项研究中，我们发现骨形态发生蛋白受体2（BMPR 2）是植入后生理和生育所必需的。尽管正常着床和早期胎盘/胎儿发育，但小鼠子宫蜕膜中Bmpr 2的缺失引发了妊娠中期蜕膜化异常，导致血管发育异常、滋养层缺陷和子宫自然杀伤细胞缺乏。子宫蜕膜中BMPR 2信号传导的缺乏因此抑制IL-15、VEGF、血管生成素和玉米信号传导。这些途径的破坏共同导致胎盘萎缩、胎儿死亡和雌性不育，从而将BMPR 2置于调节母体-胎儿界面处的几种生理信号传导途径和事件的中心点。由于滋养层浸润和子宫血管修饰与人类正常胎盘形成和胎儿生长有关，我们的研究结果表明，子宫BMPR 2介导的信号通路异常可能对维持妊娠的女性产生灾难性后果。
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 corn 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.