Li Xilong, Large Michael J, Creighton Chad J, Lanz Rainer B, Jeong Jae-Wook, Young Steven L, Lessey Bruce A, Palomino Wilder A, Tsai Sophia Y, Demayo Francesco J
Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
Mol Endocrinol. 2013 Dec;27(12):2041-54. doi: 10.1210/me.2013-1191. Epub 2013 Oct 31.
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis, and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. We observed that, as in mice, COUP-TFII is robustly expressed in the endometrial stroma of healthy women, and its expression is reduced in the ectopic lesions of women with endometriosis. To interrogate the role of COUP-TFII in human endometrial function, we used a small interfering RNA-mediated loss of function approach in primary human endometrial stromal cells. Attenuation of COUP-TFII expression did not completely block decidualization; rather it had a selective effect on gene expression. To better elucidate the role of COUP-TFII in endometrial stroma cell biology, the COUP-TFII transcriptome was defined by pairing microarray comparison with chromatin immunoprecipitation followed by deep sequencing. Gene ontology analysis demonstrates that COUP-TFII regulates a subset of genes in endometrial stroma cell decidualization such as those involved in cell adhesion, angiogenesis, and inflammation. Importantly this analysis shows that COUP-TFII plays a role in controlling the expression of inflammatory cytokines. The determination that COUP-TFII plays a role in inflammation may add insight into the role of COUP-TFII in embryo implantation and in endometrial diseases such as endometriosis.
鸡卵清蛋白上游启动子转录因子II(COUP - TFII;NR2F2)是一种孤儿核受体,参与细胞命运决定、器官发生、血管生成和代谢。小鼠子宫中COUP - TFII的缺失会导致胚胎着床缺陷和子宫基质细胞蜕膜化受损,从而引起不孕。尽管COUP - TFII在小鼠子宫蜕膜化中的功能已有描述,但其在人子宫中的作用仍不清楚。我们观察到,与小鼠一样,COUP - TFII在健康女性的子宫内膜基质中大量表达,而在子宫内膜异位症女性的异位病灶中其表达降低。为了探究COUP - TFII在人子宫内膜功能中的作用,我们在原代人子宫内膜基质细胞中采用了小干扰RNA介导的功能缺失方法。COUP - TFII表达的减弱并未完全阻断蜕膜化;相反,它对基因表达有选择性影响。为了更好地阐明COUP - TFII在子宫内膜基质细胞生物学中的作用,通过将微阵列比较与染色质免疫沉淀随后进行深度测序相结合来定义COUP - TFII转录组。基因本体分析表明,COUP - TFII调节子宫内膜基质细胞蜕膜化中的一部分基因,如那些参与细胞黏附、血管生成和炎症的基因。重要的是,该分析表明COUP - TFII在控制炎性细胞因子的表达中起作用。确定COUP - TFII在炎症中起作用可能会为其在胚胎着床以及子宫内膜疾病如子宫内膜异位症中的作用提供新的见解。