Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells.
OBJECTIVE
To investigate the influence of hCG on trophoblastic matrix metalloproteinases (MMPs) -2 and -9 as well as endometrial tissue inhibitor of metalloproteinases (TIMPs) -1, -2, and -3.


METHODS
In vitro experiment.


METHODS
Research laboratory at a university medical center.


METHODS
Women undergoing legal abortions and premenopausal women undergoing hysterectomy for benign reasons.


METHODS
Human first trimester cytotrophoblasts and decidualized endometrial stromal cells were incubated with recombinant hCG.


METHODS
Trophoblastic MMP-2 and -9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and zymography, and endometrial TIMP-1, -2, and -3 were measured by real time reverse transcriptase-polymerase chain reaction and ELISA.


RESULTS
HCG increases the secretion of MMP-2 and -9 in cytotrophoblasts dose dependently. This effect occurs after 4 hours of incubation and becomes less pronounced after 24 hours. In contrast, TIMP-1, -2, and -3 are significantly reduced by hCG in endometrial stromal cells in a time- and dose-dependent manner.


CONCLUSIONS
These results suggest a regulatory role of hCG on the MMP/TIMP system at the implantation site. By increasing trophoblastic MMP secretion and reducing endometrial TIMP expression, hCG may be an important tool for the invading embryo to regulate the depth of its implantation.
Fluhr
Herbert
H
Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
Bischof-Islami
Dorina
D
Krenzer
Stefanie
S
Licht
Peter
P
Bischof
Paul
P
Zygmunt
Marek
M
D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D019714:Tissue Inhibitor of Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9