Administration of βHCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells

Gernot Hudelist, Hudelist G, Ambros Huber, Huber A, Michael Auer, Auer M, Martin Knöfler, Knöfler M, Saleh L, Leila Saleh, Hrachowitz C, Christian Hrachowitz, Johannes Huber, Huber JC, Johannes C Huber, Kubista E, Ernst Kubista, E. Kubista, M. Manavi, Mahmood Manavi, Manavi M, Martin Bilban, Christian F Singer, Singer CF
Reproductive biomedicine online · 2010 · vol. 20(5) , pp. 699–706 · doi:10.1016/j.rbmo.2010.01.010 · PMID:20395176 · W2077784786
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Human chorionic gonadotropin (βHCG) administration induced dose-dependent alterations in the gene expression profiles of human endometriotic stromal cells.

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Abstract

Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (betaHCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism, however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of betaHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that betaHCG concentrations of 0.1U/ml and higher lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a cluster analysis which identified three clusters of genes with a comparable expression pattern in response to increasing concentrations of betaHCG. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation. Stromal monocultures from eight patients, treated with and without 50U/ml of betaHCG, were then incubated and real-time polymerase chain reaction for the highly up-regulated genes PAI2, DUSP6, PLAU and MMP1 performed in order to validate the cDNA array findings in patients with endometriosis. Taken together, this study shows that betaHCG induces dose-dependent characteristic response clusters in the gene expression profile of stromal cells obtained from endometriotic lesions which could explain the differential biological responses of betaHCG in endometriosis.

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MeSH descriptors

Chorionic Gonadotropin, beta Subunit, Human Endometrium Gene Expression Stromal Cells Adult CD56 Antigen CD56 Antigen Chorionic Gonadotropin, beta Subunit, Human Chorionic Gonadotropin, beta Subunit, Human Dose-Response Relationship, Drug Endometrium Endometrium Endometrium Female Fluorescent Antibody Technique Gene Expression Humans Leukocyte Common Antigens Leukocyte Common Antigens Reverse Transcriptase Polymerase Chain Reaction

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