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Hypoxia-mediated chemotaxis and residence of macrophage in decidua by secreting VEGFA and CCL2 during normal pregnancy
in ReproductionInfiltration and residence of decidual macrophage (dM) are of great significance to pregnancy maintenance for its role in angiogenesis, placental development and inducing immune tolerance. Besides, hypoxia has now been acknowledged as an important biological event at maternal-fetal interface in the first trimester. However, whether and how hypoxia regulates biofunctions of dM remains elusive. Herein, we observed increased expression of C-C motif chemokine ligand 2 (CCL2) and residence of macrophages in decidua when comparing to secretory-phase endometrium. Moreover, hypoxia treatment on stromal cells improved migration and adhesion of dM. Mechanistically, these effects might be mediated by upregulated CCL2 and adhesion molecules (especially ICAM2 and ICAM5) on stromal cells in the presence of endogenous vascular endothelial growth factor-A (VEGFA) in hypoxia. These findings were also verified by recombinant VEGFA and indirect coculture, indicating the interaction between stromal cells and dM in hypoxia condition may facilitate dM recruitment and residence. In conclusion, VEGFA derived from hypoxic environment may manipulate CCL2/CCR2 and adhesion molecules to enhance the interactions between dM and stromal cells and thus contribute to the enrichment of macrophages in decidua during early normal pregnancy.
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