Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Shanghai Key Laboratory of Gynecologic Oncology, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
J Cell Physiol. 2019 Jul;234(7):10789-10799. doi: 10.1002/jcp.27902. Epub 2018 Dec 13.
Monocytic myeloid-derived suppressor cells (MO-MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO-MDSCs may lead to miscarriage, and which gene expression changes take place when MO-MDSCs migrate to the uterus as bone marrow-derived cells.
We used flow sorting technology to obtain MO-MDSCs from the maternal-fetal interface and bone marrow, respectively. Affymetrix 3'IVT expression profiling chip technology was used to detect the differential gene expression profiles in MO-MDSCs at the maternal-fetal interface in a mouse model of spontaneous abortion compared with the normal fertility control mice. We also compared the differential gene expression of MO-MDSCs at the maternal-fetal interface compared with bone marrow in the normal fertility control mice.
We found that 3,409 genes in MO-MDSCs were upregulated and 1,539 genes were downregulated at the maternal-fetal interface in the spontaneous abortion mice compared with the normal fertility mice. These genes are enriched in cellular components, biological processes, molecular functions, and protein binding, tumor signaling pathway, the PI3K-Akt signaling pathway, intratumoral proteoglycans, and extracellular matrix receptor interactions. Furthermore, we found that 270 genes in MO-MDSCs were upregulated and 383 genes were downregulated at the maternal-fetal interface in the normal fertility mice compared with those in the bone marrow. These genes are enriched in cellular components, biological processes, molecular functions, cell cycle, tumor transcriptional disorder, and cell adhesion molecules.
Differential gene expression in MO-MDSCs likely contributes to a successful pregnancy in fetal-maternal immunotolerance.
摘要
单核细胞来源的髓系抑制细胞（MO-MDSCs）在维持正常妊娠中发挥着重要作用。然而，尚不清楚哪些 MO-MDSC 的变化可能导致流产，以及 MO-MDSC 作为骨髓源性细胞迁移到子宫时发生了哪些基因表达变化。
我们分别使用流式分选技术从母胎界面和骨髓中获得 MO-MDSC。采用 Affymetrix 3'IVT 表达谱芯片技术检测自发流产小鼠模型母胎界面 MO-MDSC 与正常生育对照小鼠之间的差异基因表达谱。我们还比较了正常生育对照小鼠母胎界面 MO-MDSC 与骨髓之间的差异基因表达。
我们发现，与正常生育对照组相比，自发流产组母胎界面 MO-MDSC 中有 3409 个基因上调，1539 个基因下调。这些基因在细胞成分、生物过程、分子功能和蛋白质结合、肿瘤信号通路、PI3K-Akt 信号通路、肿瘤内蛋白聚糖和细胞外基质受体相互作用等方面富集。此外，我们发现，与骨髓相比，正常生育对照组母胎界面 MO-MDSC 中有 270 个基因上调，383 个基因下调。这些基因在细胞成分、生物过程、分子功能、细胞周期、肿瘤转录失调和细胞黏附分子等方面富集。
MO-MDSC 的差异基因表达可能有助于胎儿-母体免疫耐受中的成功妊娠。
