Chemokine Signaling at the Maternal-Fetal Interface

Successful mammalian pregnancy depends on orchestrated communication between maternal immune cells, decidual stromal cells and invasive trophoblasts at the maternal-fetal interface. Chemokines are small secreted proteins that direct the migration, activation and survival of leukocytes and trophoblast populations. During early gestation, gradients of CC- and CXC-motif chemokines regulate uterine natural killer cell recruitment, macrophage polarisation and dendritic cell tolerisation, thereby ensuring spiral artery remodelling and immune tolerance. Concurrently, trophoblast-derived chemokines attract maternal immune subsets to support vascularisation and homeostasis. Dysregulated chemokine signalling has been implicated in preeclampsia, recurrent miscarriage, preterm birth and infection-related placental pathology. Elucidation of key axes such as CXCL12/CXCR4, CX3CL1/CX3CR1 and CCL21/CCR7 offers prospects for targeted therapies to restore immune balance and promote healthy placentation.

Research from Nature Portfolio

An investigation into Chlamydia trachomatis infection of human endometrial stromal cells demonstrated that bacterial invasion impairs in vitro decidualisation and reshapes the stromal chemokine milieu. Infected cells exhibit marked reductions in CXCL12 and CXCL16 expression and secretion—chemokines essential for extravillous trophoblast migration. This alteration compromises trophoblast cross-talk and may underlie infection-associated pregnancy loss by destabilising the decidual environment and hindering placental development.

Chemokine Signaling at the Maternal-Fetal Interface publication trend

The graph below shows the total number of articles in chemokine signaling at the maternal-fetal interface across all publications each year (not limited to Nature Index journals).

Technical terms

Chemokine: A small secreted protein that induces directed migration of immune and other cell types by binding specific G-protein-coupled receptors.

Trophoblast: Fetal-derived placental cell lineage responsible for embryo implantation, invasion of maternal tissue and nutrient exchange.

Decidua: The specialised endometrial lining of the uterus during pregnancy, rich in stromal and immune cells that support the embryo.

CXCL12/CXCR4 axis: A chemokine ligand/receptor pair central to migration of trophoblasts and maternal immune cells, and to angiogenesis at the implantation site.

CX3CL1 (fractalkine): A unique CX3C-motif chemokine that exists in membrane-bound and soluble forms, mediating cell adhesion and chemoattraction via CX3CR1.

CCR7: A CC-chemokine receptor that binds CCL19 and CCL21, regulating migration of cells including trophoblasts and dendritic cells.

Epithelial-to-mesenchymal transition (EMT): A cellular programme by which epithelial-like trophoblasts acquire motile, invasive mesenchymal properties essential for appropriate placentation.

References

1. Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation. JCI Insight (2023).
2. Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells. International Journal of Molecular Sciences (2023).
3. CCL21/CCR7 Axis Contributes to Trophoblastic Cell Migration and Invasion in Preeclampsia by Affecting the Epithelial Mesenchymal Transition via the ERK1/2 Signaling Pathway. Biology (2023).
4. Chlamydia trachomatis infection of human endometrial stromal cells induces defective decidualisation and chemokine release. Scientific Reports (2017).