Endothelin type A receptor (ETA) expression is regulated by HOXA10 in human endometrial stromal cells.

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.