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从稽留流产胎盘细胞外囊泡的自分泌作用导致衰老：稽留流产的可能发病机制。

The Autocrine Role of Placental Extracellular Vesicles from Missed Miscarriage in Causing Senescence: Possible Pathogenesis of Missed Miscarriage.

机构信息

Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand.

Department of Family Planning, The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai 200082, China.

出版信息

Cells. 2022 Dec 1;11(23):3873. doi: 10.3390/cells11233873.

DOI:10.3390/cells11233873
PMID:36497129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9740889/
Abstract

Placental dysfunction, including senescent changes, is associated with the pathogenesis of missed miscarriage, although the underlying mechanism is unclear. Increasing evidence indicates that placenta-specific miRNAs are packaged in extracellular vesicles (EVs) from placental syncytiotrophoblasts and are released into the maternal circulation. Aberrant cargos including miRNAs in placental EVs have been reported to be associated with the pathogenesis of complicated pregnancies. In this study, we compared the miRNA profiles in EVs derived from missed miscarriage and healthy placentae and investigated possible biological pathways which may be involved in senescence, one cause of missed miscarriage. The total concentration of RNA in placental EVs was not different between the two groups. However, there were 54 and 94 differentially expressed miRNAs in placental large and small EVs from missed miscarriage compared to EVs from healthy controls. The aberrantly expressed miRNAs seen in placental EVs were also observed in missed miscarriage placentae. Gene enrichment analysis showed that some of those differentially expressed miRNAs are involved in cellular senescence, endocytosis, cell cycle and endocrine resistance. Furthermore, transfection of trophoblasts by a single senescence-associated miRNA that was differentially expressed in placental EVs derived from missed miscarriage did not cause trophoblast dysfunction. In contrast, EVs derived from missed miscarriage placenta induced senescent changes in the healthy placenta. Our data suggested that a complex of placental EVs, rather than a few differentially expressed miRNAs in placental EVs derived from missed miscarriage placentae could contribute in an autocrine manner to placental senescence, one of the causes of missed miscarriage.

摘要

胎盘功能障碍，包括衰老变化，与稽留流产的发病机制有关，尽管其潜在机制尚不清楚。越来越多的证据表明，胎盘特异性 miRNAs 被包裹在胎盘合体滋养层的细胞外囊泡 (EVs) 中，并释放到母体循环中。异常 cargos 包括胎盘 EVs 中的 miRNAs 与复杂妊娠的发病机制有关。在这项研究中，我们比较了稽留流产和健康胎盘来源的 EVs 中的 miRNA 谱，并研究了可能参与衰老的生物学途径，这是稽留流产的一个原因。两组胎盘 EVs 中的总 RNA 浓度没有差异。然而，与健康对照组相比，稽留流产胎盘来源的大、小 EVs 中有 54 和 94 个 miRNA 表达差异。在胎盘 EVs 中观察到的异常表达的 miRNAs 在稽留流产胎盘组织中也有观察到。基因富集分析显示，这些差异表达的 miRNAs 中的一些参与细胞衰老、内吞作用、细胞周期和内分泌抵抗。此外，通过转染单个在稽留流产胎盘 EVs 中差异表达的衰老相关 miRNA，不会导致滋养层功能障碍。相反，来自稽留流产胎盘的 EVs 诱导健康胎盘发生衰老变化。我们的数据表明，胎盘 EVs 的复合物，而不是来自稽留流产胎盘 EVs 中的少数差异表达 miRNAs，可以以自分泌的方式促进胎盘衰老，这是稽留流产的原因之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/d172dad6362b/cells-11-03873-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/011b44145118/cells-11-03873-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/f5fc27c34e38/cells-11-03873-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/2ab16aac7134/cells-11-03873-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/7d2c5a9140d5/cells-11-03873-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/22c12ec29c9a/cells-11-03873-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/d172dad6362b/cells-11-03873-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/011b44145118/cells-11-03873-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/f5fc27c34e38/cells-11-03873-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/2ab16aac7134/cells-11-03873-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/7d2c5a9140d5/cells-11-03873-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/22c12ec29c9a/cells-11-03873-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5466/9740889/d172dad6362b/cells-11-03873-g006.jpg

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Antioxidants (Basel). 2021 Oct 30;10(11):1742. doi: 10.3390/antiox10111742.
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Coordinated Expressional Landscape of the Human Placental miRNome and Transcriptome.
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