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DOI: 10.1055/s-0028-1088900
Oxygen regulates human Cytotrophoblast Migration by controlling Chemokine Ligand and Receptor Expression
Aims: During placentation, formation of the maternal-fetal interface depends on the invasion of uterine tissues by cytotrophoblasts. These cells integrate into maternal spiral arterioles redirect maternal blood to the fetus. Low oxygen conditions are important during early pregnancy since they initiate cytotrophoblast differentiation pathways. In this study, we analyze the effect of oxygen on chemokine-mediated cytotrophoblast migration. Result: Cytotrophoblasts, as they differentiate, upregulate a subset of chemokines and their receptors including CXCL12 (SDF–1), CXCR4, CXCR6, CCR1, and CCR7. A low oxygen environment triggers an increase in CXCR4, CXCR6, and CCR7 and a decrease CCR1 and CXCL12. In the non-gravid uterus, glandular epithelial and endothelial cells express CXCL12 while, during pregnancy, glands and decidual cells are positive for this chemokine. We also detected a CXCL12 increase in the serum of pregnant women. Hypoxia-induced CXCR4 expression stimulated cytotrophoblast migration toward its ligand, CXCL12. Conclusion: We propose that oxygen regulated expression of chemokines and their receptors in human cytotrophoblasts plays a important functional role during placentation. Given that interactions between oxygen tension and differentiation pathways are known to regulate placental development, both direct and indirect mechanisms are likely responsible for the modulation of chemokine-mediated migration pathways during this process. As impairment of uterine invasion is implicated in the etiology of preeclampsia, intrauterine growth restriction and pregnancy loss, our findings provide additional mechanistic insight into the pathogenesis of these pregnancy complications.
Chemokine - Hypoxie - Implantation - Trophoblast