Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Department of Fetal Medicine Center, Jiaxing Maternity and Child Health Care Hospital, Jiaxing University Affiliated Women and Children Hospital, Jiaxing 314050, China.
Exp Biol Med (Maywood). 2022 Mar;247(6):488-497. doi: 10.1177/15353702211060517. Epub 2021 Dec 6.
Among different types of congenital heart diseases, ventricular septal defect is the most frequently diagnosed type and is frequently missed in early prenatal screening programs. Herein, we explored the role of maternal serum-derived exosomes in detecting and predicting ventricular septal defect in fetuses in the early stage of pregnancy. A total of 104 pregnant women consisting of 52 ventricular septal defect cases and 52 healthy controls were recruited. TMT/iTRAQ proteomic analysis uncovered 15 maternal serum exosomal proteins, which showed differential expression between ventricular septal defect and control groups. Among these, four down-regulated proteins, lactoferrin, SBSN, DCD, and MBD3, were validated by Western blot. The protein lactoferrin was additionally verified by ELISA which was able to distinguish ventricular septal defects from controls with area under the ROC curve (AUC) 0.804 (p < 0.001). Our findings reveal that lactoferrin in maternal serum-derived exosomes may be a potential biomarker for non-invasive prenatal diagnosis of fetal ventricular septal defects.
在不同类型的先天性心脏病中，室间隔缺损是最常见的类型，在早期产前筛查计划中经常被漏诊。在此，我们探讨了母体外泌体在检测和预测妊娠早期胎儿室间隔缺损中的作用。共招募了 104 名孕妇，其中 52 例为室间隔缺损，52 例为健康对照组。TMT/iTRAQ 蛋白质组学分析揭示了 15 种母体外泌体蛋白，这些蛋白在室间隔缺损组和对照组之间表现出差异表达。其中，乳铁蛋白、SBSN、DCD 和 MBD3 这 4 种下调蛋白通过 Western blot 得到验证。乳铁蛋白蛋白通过 ELISA 进一步验证，其对室间隔缺损的区分能力具有 ROC 曲线下面积（AUC）为 0.804（p<0.001）。我们的研究结果表明，母体外泌体中的乳铁蛋白可能是胎儿室间隔缺损无创性产前诊断的潜在生物标志物。
