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妊娠中的巨噬细胞时钟:蜕膜巨噬细胞的昼夜节律与代谢调控

Macrophage clock of pregnancy: circadian and metabolic control of decidual macrophage.

作者信息

Yang Dongyong, Thiele Kristin, Yin Tailang, Diao Lianghui

机构信息

Reproductive Medicine Center, Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430072, China.

Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany.

出版信息

Semin Immunopathol. 2025 Jul 18;47(1):30. doi: 10.1007/s00281-025-01057-6.

Abstract

The temporal regulation of immune responses during pregnancy is crucial for successful gestation. Yet, the specific mechanisms controlling macrophage function across gestational stages remain poorly understood. Here, we introduce the concept of the "macrophage clock of pregnancy", describing how molecular clock and cellular metabolism coordinate macrophage function across gestational stages. The molecular mechanisms underlying circadian control of macrophage function are examined, as well as hormones secreted by the pineal gland and their relevance to pregnancy-related processes. These pathways orchestrate key macrophage functions in pregnancy: modifying the uterine epithelium during implantation, supporting spiral artery remodeling, maintaining fetal tolerance, and initiating labor. Recent evidence shows that environmental factors such as shift work and extension of artificial light exposure can disturb macrophage function. The temporal regulation of macrophages also depends on metabolic signals, with distinct patterns of glycolysis, oxidative phosphorylation, and fatty acid metabolism corresponding to different gestational phases. Disruption of these temporal and metabolic signals - whether through circadian misalignment or metabolic dysfunction - correlates with pregnancy complications including recurrent pregnancy loss, preeclampsia, and preterm birth. We propose that monitoring macrophage temporal dynamics could provide early indicators of pregnancy complications, while targeting clock-controlled pathways may offer new therapeutic strategies. Understanding the temporal aspects of macrophage function opens new approaches for treating pregnancy disorders through precise immunological timing.

摘要

孕期免疫反应的时间调控对于成功妊娠至关重要。然而,跨孕期控制巨噬细胞功能的具体机制仍知之甚少。在此,我们引入“妊娠巨噬细胞时钟”的概念,描述分子时钟和细胞代谢如何在整个孕期协调巨噬细胞功能。研究了巨噬细胞功能昼夜节律控制的分子机制,以及松果体分泌的激素及其与妊娠相关过程的相关性。这些途径在妊娠中协调巨噬细胞的关键功能:在着床期间修饰子宫上皮、支持螺旋动脉重塑、维持胎儿耐受性以及启动分娩。最近的证据表明,诸如轮班工作和延长人工光照等环境因素会干扰巨噬细胞功能。巨噬细胞的时间调控还取决于代谢信号,糖酵解、氧化磷酸化和脂肪酸代谢的不同模式与不同的孕期阶段相对应。这些时间和代谢信号的破坏——无论是通过昼夜节律失调还是代谢功能障碍——都与包括复发性流产、先兆子痫和早产在内的妊娠并发症相关。我们提出,监测巨噬细胞的时间动态可以提供妊娠并发症的早期指标,而针对时钟控制的途径可能会提供新的治疗策略。了解巨噬细胞功能的时间方面为通过精确的免疫时间治疗妊娠疾病开辟了新途径。

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