Differential gene expression profile in monocytic myeloid-derived suppressor cells at maternal-fetal interface in a mouse model of spontaneous abortion.

Abstract

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.