Endothelin Type A Receptor (ETA) Expression Is Regulated by HOXA10 in Human Endometrial Stromal Cells

Abstract

Endothelin type A receptor (ET_A) is a member of the superfamily of G protein-coupled receptors. Our laboratory conducted a microarray screen that identified ET_A as target of HOXA10 transcriptional control in endometrium. Here, we confirm HOXA10-regulated ET_A expression in endometrium. Endometrial biopsies were obtained from fertile reproductive-age individuals, and first trimester decidual samples were obtained at the time of elective termination. Immunohistochemistry (IHC) was used to identify ET_A protein in endometrium as well as first trimester decidua. ET_A was expressed in endometrial stromal cells throughout the menstrual cycle. ET_A was also highly expressed in first trimester decidual cells. The regulatory relationship between HOXA10 and ET_A was established by transient transfection analysis. The human endometrial stromal cell line (HESC) and the human endometrial epithelial cell line (Ishikawa) were transfected with pcDNA/HOXA10, HOXA10 small interfering RNA (siRNA), or respective controls. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to determine expression levels of HOXA10 and ET_A in each group. ET_A gene expression increased 9-fold (P < .05) after pcDNA/HOXA10 transfection of HESC. ET_A was not regulated by HOXA10 in Ishikawa cells. We conclude that ET_A is expressed in normal endometrium and decidua. Expression of this receptor is regulated by an essential mediator of endometrial receptivity, HOXA10. ET_A may enhance the proliferative potential of endometrial cells in a manner similar to that seen in vascular smooth muscle cells. ET_A likely acts as a molecular mechanism by which HOXA10 promotes stromal cell growth and prostaglandin production in both the implantation window and decidua.

Keywords

ETA HOXA10 endometrium decidua.

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