Department of Obstetrics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou 317000, Zhejiang Province, PR China.
Center of Reproductibe Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Shanghai, PR China.
Int Immunopharmacol. 2020 Nov;88:106981. doi: 10.1016/j.intimp.2020.106981. Epub 2020 Sep 22.
Spontaneous abortion is a common disease in human pregnancy. Increasing evidence suggests that proper function of trophoblasts and immune balance of the maternal-fetal interface are crucial for successful pregnancy. Macrophages are involved in the maternal-fetal immune microenvironment. However, mechanisms associated with how macrophages impair trophoblasts' function in spontaneous abortion remain to be explored.
Firstly, the characteristics of the isolated macrophage-derived exosomes were verified by TEM and Western blot. Then, we established the co-culture of macrophage-derived exosomes with trophoblasts, and explored the role of the exosomes in trophoblasts. Moreover, expression of miR-153-3p in the macrophage-derived exosomes was detected. A miR-153-3p mimic was transfected into trophoblasts to investigate its function in the biological functions of trophoblast cells. MRNA and protein expressions were detected by qRT-PCR and Western blot. CCK8 assay was performed to measure cell proliferation and Transwell assay was utilized to examine migration of trophoblasts.
Compared with those in normal pregnant women, decidual macrophage-derived exosomes from unexplained recurrent spontaneous abortion (URSA) patients suppressed the proliferation and migration of trophoblast cells through the IDO/STAT3 pathway. MiR-153-3p was highly expressed in exosomes released from decidual macrophages of URSA patients. Transfecting miR-153-3p mimics into trophoblast cells directly inhibited IDO genes, which suppressed STAT3 pathway activation, regulating the biological behavior of trophoblast cells.
This study outlines the role of decidual macrophage-derived exosomal miR-153-3p in successful pregnancy maintenance, paving a new approach for the development of novel treatments for URSA.
自然流产是人类妊娠中的一种常见病。越来越多的证据表明，滋养细胞的正常功能和母胎界面的免疫平衡对于成功妊娠至关重要。巨噬细胞参与母胎免疫微环境。然而，关于巨噬细胞如何损害自然流产中滋养细胞功能的机制仍有待探索。
首先，通过 TEM 和 Western blot 验证分离的巨噬细胞衍生外泌体的特征。然后，我们建立了巨噬细胞衍生外泌体与滋养细胞的共培养体系，探讨了外泌体对滋养细胞的作用。此外，检测了巨噬细胞衍生外泌体中的 miR-153-3p 表达。将 miR-153-3p 模拟物转染到滋养细胞中，研究其在滋养细胞生物学功能中的作用。通过 qRT-PCR 和 Western blot 检测 mRNA 和蛋白表达。通过 CCK8 测定法测量细胞增殖，通过 Transwell 测定法检测滋养细胞的迁移。
与正常妊娠妇女相比，不明原因复发性自然流产（URSA）患者的蜕膜巨噬细胞衍生外泌体通过 IDO/STAT3 通路抑制滋养细胞的增殖和迁移。URSA 患者蜕膜巨噬细胞释放的外泌体中 miR-153-3p 表达水平较高。将 miR-153-3p 模拟物转染到滋养细胞中可直接抑制 IDO 基因，抑制 STAT3 通路的激活，调节滋养细胞的生物学行为。
本研究概述了蜕膜巨噬细胞衍生外泌体 miR-153-3p 在维持成功妊娠中的作用，为开发 URSA 的新治疗方法开辟了新途径。
