Glycodelin-A as a modulator of trophoblast invasion
Authors: Lam, Kevin K.W.; Chiu, Philip C.N.; Chung, Man-Kin; Lee, Cheuk-Lun; Lee, Kai-Fai; Koistinen, Riitta; Koistinen, Hannu; Seppala, Markku; Ho, Pak-Chung; Yeung, William S.B.
Source: Human Reproduction, Volume 24, Number 9, 28 September 2009 , pp. 2093-2103(11)
Publisher: Oxford University Press
Abstract:BACKGROUNDTrophoblast invasion is crucial to placentation. The relationship between decidual glycodelin-A and trophoblast invasion is not known.METHODSInvasiveness 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.RESULTSGlycodelin-A bound to TEV-1 cells. At a concentration of 1 g/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.CONCLUSIONSGlycodelin-A inhibits the invasion of extravillous cytotrophoblasts mainly by suppressing the activity of MMP2 and MMP9 in a glycosylation-dependent fashion.
Document Type: Research article
Publication date: 2009-09-28
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.