Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.

Abstract

Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.