Lee Kevin Y, Jeong Jae-Wook, Wang Jinrong, Ma Lijiang, Martin James F, Tsai Sophia Y, Lydon John P, DeMayo Francesco J
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Mol Cell Biol. 2007 Aug;27(15):5468-78. doi: 10.1128/MCB.00342-07. Epub 2007 May 21.
The process of implantation, necessary for all viviparous birth, consists of tightly regulated events, including apposition of the blastocyst, attachment to the uterine lumen, and differentiation of the uterine stroma. In rodents and primates the uterine stroma undergoes a process called decidualization. Decidualization, the process by which the uterine endometrial stroma proliferates and differentiates into large epithelioid decidual cells, is critical to the establishment of fetal-maternal communication and the progression of implantation. The role of bone morphogenetic protein 2 (Bmp2) in regulating the transformation of the uterine stroma during embryo implantation in the mouse was investigated by the conditional ablation of Bmp2 in the uterus using the (PR-cre) mouse. Bmp2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Bmp2fl/fl (termed Bmp2d/d) uterus. While littermate controls average 0.9 litter of 6.2+/-0.7 pups per month, Bmp2d/d females are completely infertile. Analysis of the infertility indicates that whereas embryo attachment is normal in the Bmp2d/d as in control mice, the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Recombinant human BMP2 can partially rescue the decidual response, suggesting that the observed phenotypes are not due to a developmental consequence of Bmp2 ablation. Microarray analysis demonstrates that ablation of Bmp2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and the induction of prostaglandin synthase 2 (Ptgs2). Taken together, these data demonstrate that Bmp2 is a critical regulator of gene expression and function in the murine uterus.
对于所有胎生分娩而言，着床过程必不可少，它由一系列严格调控的事件组成，包括囊胚的定位、与子宫腔的附着以及子宫基质的分化。在啮齿动物和灵长类动物中，子宫基质会经历一个称为蜕膜化的过程。蜕膜化是子宫子宫内膜基质增殖并分化为大型类上皮蜕膜细胞的过程，对于建立胎儿与母体的沟通以及着床的进展至关重要。利用（PR-cre）小鼠通过子宫内Bmp2的条件性缺失来研究骨形态发生蛋白2（Bmp2）在小鼠胚胎着床期间调节子宫基质转化中的作用。通过实时PCR分析在PR-cre；Bmp2fl/fl（称为Bmp2d/d）子宫中证实了Bmp2基因的缺失。虽然同窝对照平均每月产0.9窝，每窝6.2±0.7只幼崽，但Bmp2d/d雌性完全不育。对不育情况的分析表明，与对照小鼠一样，Bmp2d/d中的胚胎附着正常，但子宫基质无法发生蜕膜反应以支持进一步的胚胎发育。重组人BMP2可以部分挽救蜕膜反应，这表明观察到的表型并非由于Bmp2缺失的发育后果所致。微阵列分析表明，Bmp2的缺失导致特定基因变化，包括Wnt信号通路、孕激素受体（PR）信号通路的破坏以及前列腺素合酶2（Ptgs2）的诱导。综上所述，这些数据表明Bmp2是小鼠子宫中基因表达和功能的关键调节因子。
