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胎盘外泌体与子痫前期:正常妊娠以及早发型和晚发型子痫前期妊娠中的母体循环水平

Placental exosomes and pre-eclampsia: Maternal circulating levels in normal pregnancies and, early and late onset pre-eclamptic pregnancies.

作者信息

Pillay Preenan, Maharaj Niren, Moodley Jagidesa, Mackraj Irene

机构信息

Discipline of Human Physiology, School of Basic Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

Prince Mshiyeni Memorial Hospital, Department of Obstetrics and Gynaecology, Durban, South Africa.

出版信息

Placenta. 2016 Oct;46:18-25. doi: 10.1016/j.placenta.2016.08.078. Epub 2016 Aug 21.

Abstract

INTRODUCTION AND AIM

Exosomes are a subtype of extracellular vesicle (20-130 nm) released by biological cells under normal and pathological conditions. Although there have been reports of circulating exosomes in normal pregnancy, the relevance of placental-derived exosomes in normal and abnormal pregnancies still needs to be elucidated. The aim of this study was to quantify total and placental-derived exosomes in maternal plasma from normal (N), early onset- and late onset-preeclampsia (PE).

METHOD

Plasma samples were obtained from pregnant women in the third trimester, for the isolation of exosomes by differential ultracentrifugation. Total exosomes were quantified using nanoparticle tracking analysis and immuno-reactive exosomal CD63 quantification. Placental-derived exosomes were quantified using placental alkaline phosphatase (PLAP) as a specific marker. The contribution of placental-derived exosomes to total exosomes in maternal plasma was determined by the ratio of PLAP exosomes to CD63 exosomes.

RESULTS

The concentration of total exosomes significantly increased in early onset-PE and late onset-PE compared to N (≤33 weeks) and N (≥34 weeks). The relative concentration of placental-derived exosomes significantly increased in early onset-PE but decreased in late onset-PE compared to N. The ratio of PLAP exosomes to total number of exosomes significantly decreased in early onset-PE and late onset-PE. A positive correlation between total and placental-derived exosomes were obtained in N (≤33 weeks: Pearson's r = 0.60, ≥34 weeks: Pearson's r = 0.67) and early onset-PE (Pearson's r = 0.51, p < 0.05) with the inverse in late onset-PE (Pearson's r = -0.62, p < 0.01).

CONCLUSION

The differences in the contribution of placental-derived exosomes to total exosomes in maternal circulation suggests a possible pathophysiological role of placental-derived exosomes in pre-eclampsia.

摘要

引言与目的

外泌体是生物细胞在正常和病理条件下释放的一种细胞外囊泡亚型(20 - 130纳米)。尽管已有关于正常妊娠中循环外泌体的报道,但胎盘来源的外泌体在正常和异常妊娠中的相关性仍有待阐明。本研究的目的是对正常妊娠(N)、早发型和晚发型子痫前期(PE)孕妇血浆中的总外泌体和胎盘来源的外泌体进行定量。

方法

采集孕晚期孕妇的血浆样本,通过差速超速离心法分离外泌体。使用纳米颗粒跟踪分析和免疫反应性外泌体CD63定量来测定总外泌体。使用胎盘碱性磷酸酶(PLAP)作为特异性标志物来定量胎盘来源的外泌体。通过PLAP外泌体与CD63外泌体的比率来确定胎盘来源的外泌体在孕妇血浆总外泌体中的占比。

结果

与≤33周的N组和≥34周的N组相比,早发型PE组和晚发型PE组的总外泌体浓度显著增加。与N组相比,早发型PE组中胎盘来源外泌体的相对浓度显著增加,而晚发型PE组中则降低。早发型PE组和晚发型PE组中PLAP外泌体与外泌体总数的比率显著降低。在≤33周的N组(Pearson相关系数r = 0.60)、≥34周的N组(Pearson相关系数r = 0.67)和早发型PE组(Pearson相关系数r = 0.51,p < 0.05)中,总外泌体与胎盘来源外泌体呈正相关,而在晚发型PE组中呈负相关(Pearson相关系数r = -0.62,p < 0.01)。

结论

胎盘来源的外泌体在孕妇循环总外泌体中的占比差异表明胎盘来源的外泌体在子痫前期可能具有病理生理作用。

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