A Hypoxia–Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage
Abstract
:1. Introduction
2. Dynamic Changes of Blood Oxygen Concentration at the Maternal–Fetal Interface during Gestation
3. The Pivotal Function of Dmφs in Normal Pregnancy
4. Hypoxia Promotes DMφs Infiltration and Residence
5. Hypoxia Induces the Polarization of DMφs
6. Hypoxia Regulates Efferocytosis of DMφs to Maintain Tissue Homeostasis
7. Abnormality of Hypoxia-DMφ Regulatory Axis Impels Spontaneous Abortion
8. Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Molecule | Polarization | Mechanism | Correlation with Oxygen | References |
---|---|---|---|---|
Lactate | M2 M1 | Activating SRC-LDHA-VEGF Activating HIF-1α-SRC-LDHA | Inducing M2 polarization in normoxia and M1 polarization in hypoxia conditions | [63] |
ROS | M1 | Activating NF-kB pathways | Heaps up in the deficiency of oxygen | [65] |
PPARγ | M2 | Inhibiting NF-κB, STAT, AP-1 pathways | Impaired under placental hypoxia; Sirt1 can reverse this effect | [76] |
IL-6 | M2 | Activating STAT3 pathways | Low oxygen (≤5%) suppresses IL-6; hypoxia/reoxygenation (0.5% to 8%) increases IL-6 | [70,72] |
RANKL | M2 | Intervening in Akt/STAT6 signaling; increasing Jmjd3/IRF4 expression | [53,74] |
Molecule | Influence on Phagocytosis | Mechanism | Impact of Oxygen Level on Phagocytosis | References |
---|---|---|---|---|
NADPH | Enhancing phagocytosis | A noncanonical pentose phosphate pathway (PPP) during chronic hypoxia | Strengthened under hypoxia | [81] |
IL-33/ST2 | Regulating phagocytosis to avoid excessive activity | Controlling phagocytosis via PI3K/AKT and ERK1/2 pathways, inhibiting AXL | Inhibited by sST2 under hypoxia/reoxygenation | [79,82] |
VIP | Enhancing phagocytosis | Promoting IL-10 release from decidua, potentially enhancing phagocytosis | Strengthened under hypoxia via FAO | [88,89] |
SPM | Enhancing phagocytosis | Potential benefits for phagocytosis | [90] |
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Huang, X.; Lin, Z.; Zheng, Z.-M.; Shi, J.-L.; Lu, K.-Y.; Wang, J.-R.; Li, M.-Q.; Shao, J. A Hypoxia–Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage. Int. J. Mol. Sci. 2024, 25, 9710. https://doi.org/10.3390/ijms25179710
Huang X, Lin Z, Zheng Z-M, Shi J-L, Lu K-Y, Wang J-R, Li M-Q, Shao J. A Hypoxia–Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage. International Journal of Molecular Sciences. 2024; 25(17):9710. https://doi.org/10.3390/ijms25179710
Chicago/Turabian StyleHuang, Xu, Zhi Lin, Zi-Meng Zheng, Jia-Lu Shi, Ke-Yu Lu, Jia-Rui Wang, Ming-Qing Li, and Jun Shao. 2024. "A Hypoxia–Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage" International Journal of Molecular Sciences 25, no. 17: 9710. https://doi.org/10.3390/ijms25179710