Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), ICGON, IDIBAPS, Universitat de Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine + Biomedical Sciences, The University of Queensland, Australia.
Placenta. 2018 Apr;64:34-43. doi: 10.1016/j.placenta.2018.02.006. Epub 2018 Mar 2.
Placenta-derived exosomes may represent an additional pathway by which the placenta communicates with the maternal system to induce maternal vascular adaptations to pregnancy and it may be affected during Fetal growth restriction (FGR). The objective of this study was to quantify the concentration of total and placenta-derived exosomes in maternal and fetal circulation in small fetuses classified as FGR or small for gestational age (SGA).
Prospective cohort study in singleton term gestations including 10 normally grown fetuses and 20 small fetuses, sub-classified into SGA and FGR accordingly to birth weight (BW) percentile and fetoplacental Doppler. Exosomes were isolated from maternal and fetal plasma and characterized by morphology, enrichment of exosomal proteins, and size distribution by electron microscopy, western blot, and nanoparticle tracking analysis, respectively. Total and specific placenta-derived exosomes were determined using quantum dots coupled with CD63 and placental-type alkaline phosphatase (PLAP) antibodies, respectively.
Maternal concentrations of CD63 and PLAP exosomes were similar between the groups (all p > 0.05). However, there was a significant positive correlation between the ratio of placental-derived to total exosomes (PLAP ratio) and BW percentile, [rho = 0.77 (95% CI: 0.57 to 0.89); p = 0.0001]. The contribution of placental exosomes to the total exosome concentration in maternal and fetal circulation showed a significant decrease among cases, with lower PLAP ratios in FGR compared to controls and SGA cases.
Quantification of placental exosomes in maternal plasma reflects fetal growth and it may be a useful indicator of placental function.
胎盘来源的外泌体可能代表胎盘与母体系统进行通讯的另一种途径，以诱导母体血管适应妊娠，并且在胎儿生长受限 (FGR) 期间可能会受到影响。本研究的目的是定量测量小胎儿（分类为 FGR 或小于胎龄儿（SGA））的母血和胎血循环中总胎盘来源外泌体和胎盘来源外泌体的浓度。
对单胎足月妊娠进行前瞻性队列研究，包括 10 例正常生长胎儿和 20 例小胎儿，根据出生体重 (BW) 百分位和胎儿胎盘多普勒超声将小胎儿进一步分为 SGA 和 FGR。通过形态学、外泌体蛋白富集和电子显微镜、western blot 和纳米颗粒跟踪分析分别检测胎儿和母体外泌体的大小分布，对母血和胎血中的外泌体进行分离并进行鉴定。使用量子点偶联 CD63 和胎盘型碱性磷酸酶 (PLAP) 抗体分别测定总胎盘来源外泌体和特异性胎盘来源外泌体。
各组间母血 CD63 和 PLAP 外泌体浓度无差异（均 p>0.05）。然而，胎盘来源外泌体与总外泌体的比值（PLAP 比值）与 BW 百分位呈显著正相关 [rho=0.77（95%CI：0.57 至 0.89）；p=0.0001]。母血和胎血中胎盘来源外泌体占总外泌体浓度的比例在病例中明显下降，FGR 组的 PLAP 比值明显低于对照组和 SGA 组。
母血中外泌体的定量反映了胎儿的生长情况，可能是胎盘功能的有用指标。
