The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells1

Abstract

Chemokines and chemokine receptors have been implicated as pivotal players in many physiological and pathological situations, but little is known about the expression and function of chemokines and chemokine receptors at the materno-fetal interface. In this study, we first analyzed the transcription of 18 chemokine receptors in first-trimester human trophoblast cells. Among these receptors, CXCR4 was found highly transcribed. We demonstrated afterward that both CXCR4 and CXCL12 (stromal cell-derived factor-1; SDF-1) were expressed in trophoblast cells. Primary cultured trophoblast cells were also found secreting CXCL12 spontaneously. To identify the functional role of CXCR4/CXCL12 in these cells, we treated trophoblast cells with recombinant human (rh)SDF-1 alpha and analyzed the cell viability and signaling pathway. The results showed that rhSDF-1 alpha increased the viability of trophoblast cells and the activation of extracellular signal-regulated kinases signaling pathway in vitro. Our findings suggest that first-trimester trophoblast cells express functional CXCR4/CXCL12, which may play an important role in early pregnancy such as stimulating trophoblast cell proliferation or differentiation in an autocrine manner.

The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

“…19 The densities of the recovered DSCs or decidual mononuclear cells were between 1.042 and 1.062 g/ml, and between 1.062 and 1.077 g/ml, respectively. The cells were cultured in DMEM/ F12 or RPMI-1640 complete medium supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 mg/ml streptomycin in 5% CO 2 at 37 uC.…”

“…The first-trimester human villous and decidual tissues were obtained from 30 Isolation and primary culture of human first-trimester trophoblast cells Trophoblast cells were isolated by trypsin-DNase I digestion and discontinuous Percoll gradient centrifugation, as described in our previous studies, 19,23 and were cultured in Dulbecco's modified Eagle medium (DMEM)-high-glucose complete medium (2 mM glutamine, 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 100 IU/ml penicillin and 100 mg/ml streptomycin) supplemented with 20% heat-inactivated fetal bovine serum (Invitrogen, Carlsbad, CA, USA) in 5% CO 2 at 37 uC.…”

“…23 Recently, we have confirmed that the first-trimester human trophoblast cells secrete chemokine (C-X-C motif) ligand 12 (CXCL12) which, in addition to inducing trophoblast proliferation and mediating crosstalk between trophoblasts and DSCs, can also recruit CD56 bright CD16 2 natural killer cells into the decidua by its interaction with chemokine (C-X-C motif) receptor 4 (CXCR4). 19,20,24 All these observations suggest that the chemokine CXCL12/CXCR4 signal might play an important role in the cross-talk between different functional cell types at the human maternal/fetal interface.…”

“…DSCs can operate with trophoblasts in modulating trophoblast invasiveness and placentation. 19,20 DSCs and trophoblasts can produce macrophage inhibitory cytokine 1 which modulates the dendritic cell phenotype with a tolerogenic subtype in decidua. 21 As a key component of human placenta, trophoblasts are the only embryo-derived cells that interact directly with mother-derived cells.…”

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

“…20 Briefly, the obtained placenta tissue was digested and gently agitated with 0.25% trypsin and 1500 IU/ml DNase type I (AppliChem GmbH, Germany) at 37 uC for 10 min. The filtrated cell suspensions were carefully layered on a discontinuous Percoll gradient (65%-20%, in 5% step) and centrifuged.…”