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

Fertil Steril. 2008 Oct;90(4 Suppl):1390-5. doi: 10.1016/j.fertnstert.2007.08.023. Epub 2008 Mar 4.


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.

Design: In vitro experiment.

Setting: Research laboratory at a university medical center.

Patient(s): Women undergoing legal abortions and premenopausal women undergoing hysterectomy for benign reasons.

Intervention(s): Human first trimester cytotrophoblasts and decidualized endometrial stromal cells were incubated with recombinant hCG.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.

MeSH terms

  • Cells, Cultured
  • Chorionic Gonadotropin / genetics
  • Chorionic Gonadotropin / metabolism*
  • Decidua / metabolism*
  • Endometrium / metabolism
  • Female
  • Gene Expression
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Stromal Cells / metabolism
  • Tissue Inhibitor of Metalloproteinases / genetics*
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Trophoblasts / metabolism*


  • Chorionic Gonadotropin
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9