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.
OBJECTIVE
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.


METHODS
In vitro study.


METHODS
Academic research institution.


METHODS
Women undergoing diagnostic laparoscopic surgery for endometriosis.


METHODS
Increasing concentrations of hCG, added to fibroblast monocultures from endometriotic lesions.


RESULTS
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.


CONCLUSIONS
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.
Huber
Ambros
A
Division of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
Hudelist
Gernot
G
Knöfler
Martin
M
Saleh
Leila
L
Huber
Johannes C
JC
Singer
Christian F
CF
D000328:Adult; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000302:isolation & purification* / Q000627:therapeutic use*; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
D006063:Chorionic Gonadotropin