Myeloperoxidase-mediated immature dendritic cell promotes vascular remodeling and functional placenta formation.

IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Placenta Pub Date : 2025-01-13 DOI:10.1016/j.placenta.2025.01.006
Feng Gao, Jiabin Jiang, Yunfeng Lin, Juan Tang, Yanqi Ke, Yuqing Zheng, Qingquan Chen, Qicai Liu
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Abstract

Introduction: The distribution of myeloperoxidase (MPO) and dendritic cells (DCs) in sponge trophoblast cells may contribute to the syncytialisation of trophoblast cells and the establishment of uterine placental circulation. Our previous series of studies have shown that MPO plays an important role in angiogenesis and repair, and placental vascular dysfunction can lead to serious pregnancy complications and even miscarriage.

Methods: Mouse model of MPO knockout was constructed, and the crosstalk between MPO and dendritic cells (DC) cells was investigated to determine whether MPO is involved in the pregnancy process. Abnormal decidual vasculogenesis in MPO-/- pregnant mice was also suggested by RNA-seq analysis of uterine tissues from pregnant mice. In addition, we extracted mouse BMDC, analyzed the relationship between Mpo and BMDC, and established a co-culture system between BMCD and endothelial cells.

Results: It was found that angiogenesis in the decidual tissue of MPO-/- mice was impaired in early pregnancy, while in WT mice of the same pregnancy period, MPO and DC were observed to co-localize at the site of vascular development, it was found that immature BMDC can significantly promote the tube formation ability of endothelial cells in vitro, while MPO it is the key for BMDC to maintain immature phenotype.

Discussion: In conclusion, our study reveals a new role of immature DCs induced by MPO in promoting vascular remodeling of decidual tissue and functional placental formation.

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髓过氧化物酶介导的未成熟树突状细胞促进血管重塑和功能性胎盘形成。
骨髓过氧化物酶(MPO)和树突状细胞(DCs)在海绵滋养层细胞中的分布可能有助于滋养层细胞的合胞和子宫胎盘循环的建立。我们之前的一系列研究表明,MPO在血管生成和修复中起着重要作用,胎盘血管功能障碍可导致严重的妊娠并发症甚至流产。方法:构建MPO基因敲除小鼠模型,研究MPO与树突状细胞(DC)细胞间的串扰,以确定MPO是否参与妊娠过程。MPO-/-妊娠小鼠子宫组织的RNA-seq分析也提示MPO-/-妊娠小鼠个体血管生成异常。此外,我们提取小鼠BMDC,分析Mpo与BMDC的关系,建立BMDC与内皮细胞共培养体系。结果:发现MPO-/-小鼠妊娠早期蜕膜组织血管生成功能受损,而在同一妊娠期的WT小鼠中,MPO与DC在血管发育部位共定位,发现未成熟BMDC能显著促进体外内皮细胞成管能力,而MPO是BMDC维持未成熟表型的关键。讨论:总之,我们的研究揭示了MPO诱导的未成熟dc在促进蜕膜组织血管重塑和胎盘功能形成中的新作用。
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来源期刊
Placenta
Placenta 医学-发育生物学
CiteScore
6.30
自引率
10.50%
发文量
391
审稿时长
78 days
期刊介绍: Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
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