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

Abstract

Background 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. Methods 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. Results 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. Conclusion Differential gene expression in MO‐MDSCs likely contributes to a successful pregnancy in fetal–maternal immunotolerance.

Impaired myeloid-derived suppressor cells are associated with recurrent implantation failure: A case-control study

“…Studies in human and mice report that a decreased percentage and activity of MDSCs in peripheral blood is associated with early miscarriage [9,29,33,34]. In microenvironment, MDSCs secret iNOS to catabolize L-Arg to citrullin and produce NO which downregulates the expression of the TCR ζ chain on T cells hence restrain T cells activity [14].…”

Impaired Myeloid-derived Suppressor Cells Are Associated With Recurrent Implantation Failure: A Case-Control Study

“…Köstlin and his group observed that healthy pregnant women have a signi cant accumulation of PMN-MDSCs in the blood during all stages of pregnancy [27]. Studies in human and mice report that a decreased percentage and activity of MDSCs in peripheral blood is associated with early miscarriage [9,29,33,34]. In microenvironment, MDSCs secret iNOS to catabolize L-Arg to citrullin and produce NO which downregulates the expression of the TCR ζ chain on T cells hence restrain T cells activity [14].…”