Hum. Reprod. Advance Access originally published online on June 11, 2009
Human Reproduction 2009 24(9):2093-2103; doi:10.1093/humrep/dep205
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycodelin-A as a modulator of trophoblast invasion
1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China 2 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, 00029 HUS Helsinki, Finland 3 Department of Clinical Chemistry, Helsinki University Central Hospital, 00029 HUS Helsinki, Finland
4 Correspondence address. Tel: +852-28553405; Fax: +852-28175374; E-mail: wsbyeung{at}hkucc.hku.hk
BACKGROUND: Trophoblast invasion is crucial to placentation. The relationship between decidual glycodelin-A and trophoblast invasion is not known.
METHODS: Invasiveness of First trimester extravillous cytotrophoblast-1 (TEV-1) cell line, TEV-1, cells was determined by trans-well invasion assay. The gene expression, protein secretion and activities of the matrix metalloproteinase (MMP)-2 and -9, urokinase plasminogen activator (uPA), tissue inhibitor of metalloproteinase (TIMP)-1 and -2 and plasminogen activator inhibitor (PAI-1) of glycodelin-A-treated cells were measured by quantitative PCR, ELISA and gel zymography, respectively.
RESULTS: Glycodelin-A bound to TEV-1 cells. At a concentration of 1 µg/ml, glycodelin-A, but not other glycodelin isoforms, suppressed the invasion of TEV-1 cells. The effect was glycosylation-dependent and was associated with reduction (P < 0.05) of MMP2, MMP9 and uPA activities in the conditioned medium from the treated culture. Glycodelin-A treatment suppressed the amount of MMP2 protein in the conditioned medium (P < 0.05) and MMP2 mRNA in the cells (P < 0.05), but did not affect that of MMP9. Glycodelin-A also significantly reduced the expression, secretion and activity of uPA (P < 0.05). The treatment did not affect the expression of TIMP-1, TIMP-2 or PAI-1, cell proliferation or survival of the cells.
CONCLUSIONS: Glycodelin-A inhibits the invasion of extravillous cytotrophoblasts mainly by suppressing the activity of MMP2 and MMP9 in a glycosylation-dependent fashion.
Key words: glycodelin/invasion/matrix metalloproteinase/trophoblast/urokinase plasminogen activator
Contribute equally to the article. Submitted on February 13, 2009; resubmitted on April 5, 2009; accepted on April 9, 2009.