Tong Mancy, Chen Qi, James Joanna L, Wise Michelle R, Stone Peter R, Chamley Lawrence W
Department of Obstetrics and GynaecologyThe University of Auckland, Auckland, New Zealand
Department of Obstetrics and GynaecologyThe University of Auckland, Auckland, New Zealand.
Reproduction. 2017 Jun;153(6):835-845. doi: 10.1530/REP-16-0615. Epub 2017 Mar 29.
Throughout human gestation, the placenta extrudes vast quantities of extracellular vesicles (EVs) of different sizes into the maternal circulation. Although multinucleated macro-vesicles are known to become trapped in the maternal lungs and do not enter the peripheral circulation, the maternal organs and cells that smaller placental micro-vesicles interact with remain unknown. This study aimed to characterise the interaction between placental micro-vesicles and endothelial cells and to elucidate which organs placental micro-vesicles localise to Placental macro- and micro-vesicles were isolated from cultured human first trimester placental explants by sequential centrifugation and exposed to human microvascular endothelial cells for up to 72 h. , placental macro- and micro-vesicles were administered to both non-pregnant and pregnant CD1 mice, and after two or 30 min or 24 h, organs were imaged on an IVIS Kinetic Imager. Placental EVs rapidly interacted with endothelial cells via phagocytic and clathrin-mediated endocytic processes , with over 60% of maximal interaction being achieved by 30 min of exposure. , placental macro-vesicles were localised exclusively to the lungs regardless of time of exposure, whereas micro-vesicles were localised to the lungs, liver and kidneys, with different distribution patterns depending on the length of exposure and whether the mouse was pregnant or not. The fact that placental EVs can rapidly interact with endothelial cells and localise to different organs supports that different size fractions of placental EVs are likely to have different downstream effects on foeto-maternal communication.
在人类妊娠期，胎盘会将大量不同大小的细胞外囊泡（EVs）释放到母体循环中。虽然已知多核大囊泡会滞留在母体肺部，不会进入外周循环，但较小的胎盘微囊泡与哪些母体器官和细胞相互作用仍不清楚。本研究旨在表征胎盘微囊泡与内皮细胞之间的相互作用，并阐明胎盘微囊泡定位于哪些器官。通过连续离心从培养的人类孕早期胎盘外植体中分离出胎盘大囊泡和微囊泡，并将其暴露于人类微血管内皮细胞长达72小时。此外，将胎盘大囊泡和微囊泡分别给予未怀孕和怀孕的CD1小鼠，在2分钟、30分钟或24小时后，使用IVIS Kinetic成像仪对器官进行成像。胎盘EVs通过吞噬作用和网格蛋白介导的内吞过程迅速与内皮细胞相互作用，在暴露30分钟时达到最大相互作用的60%以上。此外，无论暴露时间如何，胎盘大囊泡仅定位于肺部，而微囊泡则定位于肺部、肝脏和肾脏，其分布模式因暴露时间长短以及小鼠是否怀孕而异。胎盘EVs能够迅速与内皮细胞相互作用并定位于不同器官，这一事实支持了不同大小的胎盘EVs可能对母婴交流产生不同的下游影响。
