基于早孕期血清胎盘外泌体 miR-520a-5p 水平预测重度子痫前期及胎儿宫内生长受限
Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester.
机构信息
Obstetrics Department of Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China.
NanKai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, China.
出版信息
Medicine (Baltimore). 2024 May 17;103(20):e38188. doi: 10.1097/MD.0000000000038188.
BACKGROUND
To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy.
METHODS
During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups.
RESULTS
It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05).
CONCLUSION
Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.
背景
评估血清外泌体微小 RNA-520a-5p(miR-520a-5p)水平在妊娠早期预测严重子痫前期(sPE)和胎儿生长受限(FGR)发生的能力。
方法
在 2020 年 10 月至 2021 年 10 月期间,从嵌套病例对照研究中的 105 名孕妇中获取第一孕期的血清样本并随后冷冻保存在-80℃。该队列包括第三孕期发生 sPE(sPE 组,n=35)和 FGR(FGR 组,n=35)的孕妇,另外 35 名血压正常的孕妇为正常妊娠组。解冻后从所有组中提取第一孕期的血清样本进行进一步分析。使用透射电子显微镜、western blot 和纳米颗粒跟踪分析从第一孕期的血清样本中提取外泌体。此外,在研究过程中还确定了它们的胎盘来源。使用实时定量聚合酶链反应(qRT-PCR)检测外泌体 miR-520a-5p 水平,主要涉及定量逆转录聚合酶链反应(qRT-PCR)。使用实时定量聚合酶链反应(qRT-PCR)测量 3 组胎儿胎盘组织中的 miR-520a-5p 表达。比较血清胎盘外泌体和胎儿胎盘组织中的 miR-520a-5p 水平。在所有 3 组中,胎盘滋养细胞均被鉴定为血清外泌体的来源。
结果
与正常妊娠组相比,sPE 和 FGR 组的血清胎盘外泌体中的 miR-520a-5p 水平均较低,这与产后胎盘组织中的观察结果一致。使用第一孕期血清胎盘外泌体中的 miR-520a-5p 水平预测 sPE 的准确性明显更高(受试者工作特征曲线下面积=0.806,P<.05),而预测 FGR 的准确性(受试者工作特征曲线下面积=0.628,P<.05)较低。
结论
可以从妊娠早期孕妇的血清中提取胎盘来源的外泌体,并检测外泌体中的 miR-520a-5p。miR-520a-5p 的下调可作为预测 sPE 发生的更具预测性的指标,优于预测 FGR。