Chemokine CXCL12 promotes the cross-talk between trophoblasts and decidual stromal cells in human first-trimester pregnancy.
BACKGROUND
The precise mechanisms in the materno-fetal dialogue still remain unclear. The aim of this study was to investigate the role of the chemokine CXCL12 and its receptor CXCR4 in the interaction of trophoblasts and decidual stromal cells (DSCs).


METHODS
Expression of CXCL12/CXCR4 in trophoblasts and DSCs was detected by reverse transcription-polymerase chain reaction and immunochemical staining. The secretion of CXCL12 by trophoblasts was determined by enzyme-linked immunosorbent assay. The effects of CXCL12 on the biological functions of trophoblasts and DSCs were analyzed using a cell viability assay, matrigel invasion assay and zymography. Finally, a co-culture model was established to investigate the modulation of CXCL12/CXCR4 in the interaction of trophoblasts and DSCs.


RESULTS
CXCR4 was transcribed and translated by both human trophoblasts and DSCs. Human trophoblasts secreted CXCL12 spontaneously in vitro, but DSCs did not. CXCL12 induced an apparent increase in the invasiveness of trophoblasts (P < 0.01), and up-regulated matrix metalloproteinase (MMP) 9 and MMP2 activity of both trophoblasts and DSCs (both P < 0.01) in an autocrine and paracrine manner. The invasiveness and MMP9 and MMP2 activity of trophoblasts in co-culture with DSCs increased significantly (P < 0.01), and these could be inhibited by anti-CXCR4 neutralizing antibody.


CONCLUSIONS
CXCL12 secreted by human trophoblasts enhances the coordination between trophoblasts and DSCs, via the regulation of MMP9 and MMP2, which may improve the functional materno-fetal interface.
Zhou
Wen-Hui
WH
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai MedicalCollege, Shanghai 200011, PR China.
Du
Mei-Rong
MR
Dong
Lin
L
Yu
Jing
J
Li
Da-Jin
DJ
D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000502:physiology*; D003656:Decidua / Q000166:cytology*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology; D017154:Stromal Cells / Q000201:enzymology / Q000502:physiology*; D014327:Trophoblasts / Q000502:physiology*; D015854:Up-Regulation
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9