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蜕膜间充质干细胞功能的改变与自发性分娩的开始有关。

Functional changes in decidual mesenchymal stem/stromal cells are associated with spontaneous onset of labour.

机构信息

Department of Maternal-Fetal Medicine Pregnancy Research Centre, Royal Women's Hospital, Parkville, VIC 3052, Australia.

Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, VIC 3052, Australia.

出版信息

Mol Hum Reprod. 2020 Aug 1;26(8):636-651. doi: 10.1093/molehr/gaaa045.

Abstract

Ageing and parturition share common pathways, but their relationship remains poorly understood. Decidual cells undergo ageing as parturition approaches term, and these age-related changes may trigger labour. Mesenchymal stem/stromal cells (MSCs) are the predominant stem cell type in the decidua. Stem cell exhaustion is a hallmark of ageing, and thus ageing of decidual MSCs (DMSCs) may contribute to the functional changes in decidual tissue required for term spontaneous labour. Here, we determine whether DMSCs from patients undergoing spontaneous onset of labour (SOL-DMSCs) show evidence of ageing-related functional changes compared with those from patients not in labour (NIL-DMSCs), undergoing Caesarean section. Placentae were collected from term (37-40 weeks of gestation), SOL (n = 18) and NIL (n = 17) healthy patients. DMSCs were isolated from the decidua basalis that remained attached to the placenta after delivery. DMSCs displayed stem cell-like properties and were of maternal origin. Important cell properties and lipid profiles were assessed and compared between SOL- and NIL-DMSCs. SOL-DMSCs showed reduced proliferation and increased lipid peroxidation, migration, necrosis, mitochondrial apoptosis, IL-6 production and p38 MAPK levels compared with NIL-DMSCs (P < 0.05). SOL- and NIL-DMSCs also showed significant differences in lipid profiles in various phospholipids (phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine), sphingolipids (ceramide, sphingomyelin), triglycerides and acyl carnitine (P < 0.05). Overall, SOL-DMSCs had altered lipid profiles compared with NIL-DMSCs. In conclusion, SOL-DMSCs showed evidence of ageing-related reduced functionality, accumulation of cellular damage and changes in lipid profiles compared with NIL-DMSCs. These changes may be associated with term spontaneous labour.

摘要

衰老和分娩有共同的途径,但它们的关系仍知之甚少。随着分娩接近足月,蜕膜细胞会衰老,这些与年龄相关的变化可能会引发分娩。间充质干细胞(MSCs)是蜕膜中的主要干细胞类型。干细胞耗竭是衰老的标志,因此蜕膜间充质干细胞(DMSCs)的衰老可能导致足月自发性分娩所需的蜕膜组织的功能变化。在这里,我们确定与未分娩(NIL)患者(行剖宫产术)相比,来自自发性分娩(SOL)患者的 DMSC 是否表现出与衰老相关的功能变化。从足月(37-40 孕周)、SOL(n=18)和 NIL(n=17)健康患者的胎盘上采集了 DMSC。DMSC 从胎盘分娩后附着的蜕膜基底层中分离出来。DMSC 表现出干细胞样特性,并且具有母体来源。评估和比较了 SOL-和 NIL-DMSC 之间的重要细胞特性和脂质谱。与 NIL-DMSCs 相比,SOL-DMSCs 的增殖减少,脂质过氧化、迁移、坏死、线粒体凋亡、IL-6 产生和 p38 MAPK 水平增加(P<0.05)。与 NIL-DMSCs 相比,SOL-和 NIL-DMSCs 的各种磷脂(磷脂乙醇胺、磷脂酰甘油、磷脂酰肌醇、磷脂酰丝氨酸)、鞘脂(神经酰胺、神经鞘磷脂)、甘油三酯和酰基辅酶 A 也表现出明显的脂质谱差异(P<0.05)。总体而言,与 NIL-DMSCs 相比,SOL-DMSCs 的脂质谱发生了改变。总之,与 NIL-DMSCs 相比,SOL-DMSCs 的功能、细胞损伤积累和脂质谱发生了与衰老相关的变化。这些变化可能与足月自发性分娩有关。

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