胎盘外泌体在子宫螺旋动脉重铸不全相关妊娠并发症中的作用

摘要/Abstract

摘要： 子宫螺旋动脉重铸是胎盘滋养细胞与母体血管内皮、平滑肌细胞、免疫细胞等相互作用下完成的，细胞间信息传递在这一过程中起重要作用。外泌体的发现更新了学者们对细胞间信息传递的思考模式。外泌体是细胞主动分泌的直径40～100 nm的囊泡，可由多种细胞分泌并可从多种体液中分离出来，携带多种蛋白质、mRNA、微小RNA（miRNA）等信号分子，在细胞间通讯起重要作用。研究证明，胎盘滋养细胞能分泌外泌体，在母血中能检测并分离出胎盘外泌体，胎盘外泌体携带滋养细胞信息，作用于母体细胞，调节血管形成，重铸子宫螺旋动脉，调节母体免疫，参与胎盘屏障的形成。综述胎盘外泌体的特征、生物学功能及其在螺旋动脉重铸不全相关妊娠并发症中的变化，探讨胎盘外泌体作为诊断妊娠并发症血清标志物的临床价值。

关键词: 胎盘, 先兆子痫, 胎儿生长迟缓, 外泌体, 滋养细胞, 子宫螺旋动脉, 重铸

Abstract: Uterine spiral artery remodeling is accomplished by the interaction between the maternal vascular endothelial cells, smooth muscle cells, immune cells and placenta trophoblast cells. Cell-to-cell communication plays an important role in the process. Our understanding of how cells communicate has undergone a paradigm shift since the finding of the role of exosomes in intercellular signaling. Exosomes are automatically secreted homogenous membrane vesicles with a diameter of 40-100 nm which have been found to be released by various cell types and isolated from biological fluids. Exosomes carry a variety of mRNA, microRNA and proteins which play an important role in cell-to-cell communication. Studies have shown that exosomes can be released by placenta trophblast. Placenta exosomes can be identified and isolated in maternal blood which carry informations of trophblast acting on the target cells. The biological functions of placenta exosomes include regulating immune tolerance, remodeling of uterine spiral arteries, promoting angiogenesis and formating the placental barrier，ect. This article summarized the characteristics and functions of placenta exosomes and the changes in pregnancy complications associated with dysfunctional remodeling of uterine spiral arteries, to explore the clinical value of placenta exosomes as a serum marker in diagnosis of pregnancy complications.

Key words: Placenta, Pre-eclampsia, Fetal growth retardation, Exosomes, Trophblast, Uterine spiral artery, Remodel

徐欣然，王妍平，崔洪艳. 胎盘外泌体在子宫螺旋动脉重铸不全相关妊娠并发症中的作用[J]. 国际妇产科学杂志, 2019, 46(3): 288-292.

XU Xin-ran，WANG Yan-ping，CUI Hong-yan. The Role of Placenta Exosomes in Pregnancy Complications Associated with Dysfunctional Remodeling of Uterine Spiral Arteries[J]. Journal of International Obstetrics and Gynecology, 2019, 46(3): 288-292.

参考文献

[1]Ruivo CF，Adem B，Silva M，et al.The Biology of Cancer Exosomes: Insights and New Perspectives[J].Cancer Res, 2017, 77(23):6480-6488 [2]Mitchell MD, Peiris HN, Kobayashi M, et al.Placental exosomes in normal and complicated pregnancy[J].Am J Obstet Gynecol, 2015, 213(4 Suppl):S173-181 [3]Arenaccio C, Federico M.TheMultifaceted Functions of Exosomes in Health and Disease: An Overview[J].Adv Exp Med Biol, 2017, 20(998):3-19 [4]Pinheiro A, Silva AM, Teixeira JH, et al.Extracellular vesicles: intelligent delivery strategies for therapeutic applications[J].J Control Release, 2018, 24(289):56-69 [5]Fanale D, Taverna S, Russo A, et al.Circular RNA in Exosomes[M]. Adv Exp Med Biol, 2018, 1087:109-117. [6]Preenan Pillay, Kogi Moodley, Jagidesa Moodley, et al.Placenta-derived exosomes: potential biomarkers of preeclampsia[J].Int J Nanomedicine, 2017, 31(12):8009-8023 [7]Gerit Moser, Gregor Weiss, Monika Sundl, et al.Extravillous trophoblasts invade more than uterine arteries: evidence for the invasion of uterine veins[J].Histochem Cell Biol, 2017, 147(3):353-366 [8]Vera Rebmann, Lisa K?nig, Fabiola da Silva Nardi, et al.The Potential of HLA-G-Bearing Extracellular Vesicles as a Future Element in HLA-G Immune Biology[J].Front Immunol, 2016, 4(7):173-179 [9]Dionne Tannetta, Gavin Collett, Manu Vatish, et al.Syncytiotrophoblast extracellular vesicles – Circulating biopsies reflecting placental health[J].Placenta, 2017, 4(52):134-138 [10]Truong G, Guanzon D, Kinhal V, et al.Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells -Liquid biopsies for monitoring complications of pregnancy[J].PLoS One, 2017, ,12(3):e0174514- [11]Salomon C, Ryan J, Sobrevia L, et al.Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis[J].PLoS One, 2013, 8(7):e68451- [12]Salomon C, Yee S, Scholz-Romero K, et al.Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration[J].Front Pharmacol, 2014, 11(5):175-186 [13]Bulmer JN, Innes BA, Levey J, et al.The role of vascular smooth muscle cell apoptosis and migration during uterine spiral arteryremodeling in normal human pregnancy[J].FASEB J, 2012, 26(7):2975-85 [14]Tilburgs T, Crespo AC, van der Zwan A, et al.Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes[J].Proc Natl Acad Sci U S A, 2015, 112(23):7219-24 [15]Tilburgs T, Evans JH, Crespo AC, et al.The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface[J].Proc Natl Acad Sci U S A, 2015, 112(43):13312-133127 [16]Miranda J, Paules C, Nair S, et al.Placental exosomes profile in maternal and fetal circulation in intrauterine growth restriction - Liquid biopsies to monitoring fetal growth[J].Placenta, 2018, 4(64):34-43 [17]Ouyang Y, Bayer A, Chu T, et al.Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity[J].Placenta, 2016, 11(47):86-95 [18]Bayer A, Lennemann NJ, Ouyang Y, et al.Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling[J].Placenta, 2018, 1(61):33-38 [19]Zhang P.Decidual Vasculopathy in Preeclampsia and Spiral Artery Remodeling Revisited: Shallow Invasion versus Failure of Involution[J].AJP Rep, 2018, 8(4):e241-e246 [20]Carlos Salomon,Sarah W.Yee,Murray D. Mitchell，et al..The Possible Role of Extravillous Trophoblast-Derived Exosomes on the Uterine Spiral Arterial Remodeling under Both Normal and Pathological Conditions[J]. , [J].Biomed Res Int, 2014, :e693157- [21]Salomon C, Guanzon D, Scholz-Romero K etal.Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation[J].J Clin Endocrinol Metab, 2017, 102(9):3182-3194 [22]Pillay P, Maharaj N, Moodley J, et al.Placental exosomes and pre-eclampsia: Maternal circulating levels in normal pregnancies and,early and late onset pre-eclamptic pregnancies[J].Placenta, 2016, 10(46):18-25 [23]Zhen-yu Yao, Wen-bin Chen, Shan-shan Shao, et al.Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders [J].[J].J Zhejiang Univ Sci B. , 2018, 19(3):183-198 [24]. [25]Sammar M, Dragovic R, Meiri H, et al.Reduced placental protein 13 (PP13) in placental derived syncytiotrophoblast extracellular vesicles in preeclampsia - A novel tool to study the impaired cargo transmission of the placenta to the maternal organs[J]. [J]. Placenta., 2018, 6(66):17-25 [26]Ding J, Huang F, Wu G, et al.MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2[J].[J].PLoS One, 2015, (10):e0120321.- [27]Miura K, Higashijima A, Murakami Y, et al.Circulating chromosome 19 miRNA cluster microRNAs in pregnant women with severe pre-eclampsia[J].J Obstet Gynaecol Res, 2015, 41(10):1526-1532 [28]Shen L, Li Y, Li R, Diao Z, et al.Placenta associated serum exosomal miR 155 derived from patients with preeclampsia inhibits eNOS expression in human umbilical vein endothelial cells[J].Int J Mol Med, 2018, 41(3):1731-1739 [29]Maria Eugenia Guicciardi, Harmeet Malhi, et al.Apoptosis and Necrosis in the Liver[J].Compr Physiol, 2013, 3(2):10-19