Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Department of Pharmacy, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Biol Reprod. 2021 Jul 2;105(1):32-39. doi: 10.1093/biolre/ioab060.
Preeclampsia (PE) is a leading cause of maternal and fetal-neonatal deaths, and its pathogenesis has been linked to the involvement of extracellular vesicles (EVs). EVs are a heterogeneous group of cell-originated membranous vesicles including exosomes, microvesicles, and apoptotic bodies. EVs transport various bioactive cargos such as lipids, proteins, or nucleic acids, and thus mediate cellular communication and contribute to the proper functioning of cells, organs and processes, including normal pregnancy. Numerous studies have reported that EVs are associated with abnormal levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) in PE. EVs isolated from preeclamptic women have been implicated in trophoblast dysfunction and have been reported to activate endothelium, monocytes, and platelets, and to be involved in defective placentation, imbalanced angiogenesis, and intravascular inflammation. When injected into pregnant rodents, these EVs induced hypertension, proteinuria, and adverse fetal outcomes. Deciphering the contribution of EVs to PE will advance our current understanding of this disorder and may lead to more clinical strategies for the management of PE. Of note, the composition of EV cargos may be characteristic of the status and stages of gestation, providing researchers the possibility of one day using EVs as novel, noninvasive, biomarkers for early screening of PE. Herein, we reviewed the latest research into EVs with emphasis on their role in the pathogenesis of PE and their applications as biomarkers in the early screening of this pregnancy-specific disorder.
子痫前期 (PE) 是孕产妇和胎儿/新生儿死亡的主要原因，其发病机制与细胞外囊泡 (EVs) 的参与有关。EVs 是一组异质性的细胞起源的膜性囊泡，包括外泌体、微泡和凋亡小体。EVs 运输各种生物活性 cargo，如脂质、蛋白质或核酸，从而介导细胞间通讯，并有助于细胞、器官和过程的正常功能，包括正常妊娠。许多研究报告称，EVs 与 PE 中可溶性 fms 样酪氨酸激酶-1 (sFlt-1)、可溶性内皮糖蛋白 (sEng) 和胎盘生长因子 (PlGF) 的异常水平有关。从子痫前期妇女中分离出的 EVs 被认为与滋养层功能障碍有关，并被报道可激活内皮细胞、单核细胞和血小板，并参与胎盘功能不全、血管生成失衡和血管内炎症。当将这些 EVs 注射到怀孕的啮齿动物中时，会诱导其发生高血压、蛋白尿和不良的胎儿结局。解析 EVs 对 PE 的贡献将增进我们对这种疾病的认识，并可能为管理 PE 提供更多的临床策略。值得注意的是，EV cargos 的组成可能是其状态和妊娠阶段的特征，这为研究人员提供了有朝一日将 EVs 用作 PE 早期筛查的新型、非侵入性生物标志物的可能性。本文综述了 EVs 的最新研究进展，重点介绍了其在 PE 发病机制中的作用及其作为该妊娠特发性疾病早期筛查的生物标志物的应用。
