Petit Fabrice G, Jamin Soazik P, Kurihara Isao, Behringer Richard R, DeMayo Francesco J, Tsai Ming-Jer, Tsai Sophia Y
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6293-8. doi: 10.1073/pnas.0702039104. Epub 2007 Apr 2.
COUP-TFII (NR2F2), chicken ovalbumin upstream promoter-transcription factor II, is an orphan nuclear receptor of the steroid/thyroid hormone receptor superfamily. The Coup-tfII-null mutant mice die during the early embryonic development because of angiogenesis and heart defects. To analyze the physiological function of COUP-TFII during organogenesis, we used the cre/loxP system to conditionally inactivate COUP-TFII in the ovary and uterus. Homozygous adult female mutants with specific inactivation of the Coup-tfII gene in uterine stromal and smooth muscle cells have severely impaired placental formation, leading to miscarriage at days 10-12 of pregnancy. Deletion of the Coup-tfII gene resulted in an increase in trophoblast giant cell differentiation, a reduction of the spongiotrophoblast layer, and an absence of labyrinth formation causing an improper vascularization of the placenta. This study describes an important maternal role of COUP-TFII in regulating the placentation. The endometrial COUP-TFII might modulate the signaling between the uterus and the extraembryonic tissue for the proper formation of the placenta.
COUP-TFII（NR2F2），即鸡卵清蛋白上游启动子转录因子II，是类固醇/甲状腺激素受体超家族的一种孤儿核受体。Coup-tfII基因敲除突变小鼠在胚胎发育早期因血管生成和心脏缺陷而死亡。为了分析COUP-TFII在器官发生过程中的生理功能，我们使用cre/loxP系统在卵巢和子宫中条件性地使COUP-TFII失活。子宫基质和平滑肌细胞中Coup-tfII基因特异性失活的纯合成年雌性突变体胎盘形成严重受损，导致妊娠第10 - 12天流产。Coup-tfII基因的缺失导致滋养层巨细胞分化增加、海绵滋养层变薄以及迷路形成缺失，从而导致胎盘血管化异常。本研究描述了COUP-TFII在调节胎盘形成过程中的重要母体作用。子宫内膜中的COUP-TFII可能调节子宫与胚外组织之间的信号传导，以促进胎盘的正常形成。
