ArrayExpress Uploaderarrayexpress_sid2314myometriummyometriummyometriummyometriummyometriummyometriummyometriummyometriumFibroidFibroidFibroidendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometriumendometrium04Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood....23913972E-GEOD-47577/profile/8773/arrayexpressuploader139arterycellendometriumspiralDec.12, 2014FalseE-GEOD-47577_A-AFFY-44regulation-of-endometrial-bleeding-by-unk-cellsRegulation of endometrial bleeding by uNK cellsJul.12, 2014Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator (PRM). We now compare global endometrial gene expression in asoprisnil-treated versus control women and demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding. 39 Sampleshttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-47577humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-47577/samples/