COUP-TFII regulates human endometrial stromal genes involved in inflammation

Xilong Li, Li X, Michael J. Large, Chad J. Creighton, Creighton CJ, Lanz RB, Rainer B. Lanz, Jae‐Wook Jeong, Jeong JW, Jae-Wook Jeong, Steven L. Young, Lessey BA, Bruce A. Lessey, Palomino WA, Wilder A. Palomino, Sophia Y. Tsai, Tsai SY, Francesco J. DeMayo
Molecular Endocrinology · 2013 · vol. 27(12) , pp. 2041–2054 · doi:10.1210/me.2013-1191 · PMID:24176914 · PMC3857200 · W1982512516
Lab / animal OA: bronze CC0 ⤵ 14 in-corpus citations
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COUP-TFII is expressed in human endometrial stroma and regulates genes involved in inflammation, cell adhesion, and angiogenesis, with reduced expression in endometriosis.

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Abstract

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.

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Condition tags

endometriosisinfertility

MeSH descriptors

COUP Transcription Factor II Endometrium Endometrium Gene Expression Regulation Gene Expression Regulation Inflammation Inflammation Adolescent Adolescent Adult Adult Animals Animals Binding Sites Binding Sites Choristoma Choristoma Choristoma Choristoma Chromatin Immunoprecipitation

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