Effect of highly purified human chorionic gonadotropin preparations on the gene expression signature of stromal cells derived from endometriotic lesions: potential mechanisms for the therapeutic effect of human chorionic gonadotropin in vivo

Abstract

To investigate alterations in the overall gene expression profile of endometriosis-derived stroma with increasing concentrations of hCG by using the Affymetrix GeneChip U133 Set. In vitro study. Academic research institution. Women undergoing diagnostic laparoscopic surgery for endometriosis. Increasing concentrations of hCG, added to fibroblast monocultures from endometriotic lesions. We have found that hCG concentrations of 0.1 U/mL and higher lead to a dose-dependent increase in the expression of 68 genes. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix (ECM) remodeling, apoptosis, and inflammation. We then incubated stromal monocultures from nine patients treated with and without 50 U/mL of hCG and performed reverse transcriptase-polymerase chain reaction (RT-PCR) for selected, highly up-regulated genes to validate our DNA array findings and to confirm that the alterations in the gene expression signature are exemplary of patients with endometriosis. We have shown that hCG induces dose-dependent alterations in the gene expression profile of stromal cells obtained from endometriotic lesions and have, for the first time, identified potential mechanisms by which hCG might exert its therapeutic effect on endometriotic lesions.