Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions

Cells. 2019 Oct 31;8(11):1369. doi: 10.3390/cells8111369.


Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to 51 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.

Keywords: adhesion; extravillous trophoblasts; integrin α5β1; migration; preeclampsia; pregnancy-specific glycoproteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Movement
  • Extracellular Matrix / metabolism
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Heparitin Sulfate / metabolism
  • Humans
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / metabolism
  • Integrin alpha5beta1 / metabolism*
  • Placenta / metabolism
  • Pre-Eclampsia / diagnosis
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy-Specific beta 1-Glycoproteins / analysis
  • Pregnancy-Specific beta 1-Glycoproteins / genetics
  • Pregnancy-Specific beta 1-Glycoproteins / metabolism*
  • Protein Binding
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*


  • Immobilized Proteins
  • Integrin alpha5beta1
  • Pregnancy-Specific beta 1-Glycoproteins
  • Heparitin Sulfate
  • Focal Adhesion Protein-Tyrosine Kinases