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EMX2 is a transcription factor necessary for reproductive tract development. Sex steroids regulate endometrial HOXA10 expression, which in turn negatively regulates EMX2. In this study, we characterize menstrual cycle-dependent expression of EMX2 in endometrium from women with and without endometriosis. In the absence of endometriosis, EMX2 mRNA levels declined 50% in periimplantation endometrium compared with levels in the proliferative phase. To determine whether the decrease in endometrial EMX2 expression was regulated by endogenous endometrial HOXA10, primary endometrial stromal cells were transfected with an EMX2-reporter construct containing a HOXA10 binding site. Acting via this site, we observed HOXA10-mediated repression of reporter expression. In the endometrium of patients with endometriosis, unlike normal endometrium, EMX2 levels were not decreased in the periimplantation period. We have previously shown that up-regulation of HOXA10 in periimplantation endometrium fails to occur in women with endometriosis. To determine whether elevated endometrial EMX2 levels were due to failure of HOXA10-mediated transcriptional repression, secondary to low HOXA10 levels in endometriosis, we transfected stromal cells with HOXA10 antisense and an EMX2-reporter construct. Reporter expression was increased, indicating reversal of HOXA10-mediated transcriptional repression. Endometrial EMX2 expression is aberrant in women with endometriosis and is mediated by altered HOXA10 expression.

EMX2 Gene Expression in the Female Reproductive Tract and Aberrant Expression in the Endometrium of Patients with Endometriosis