Differentiation of the Endometrial Macrophage during Pregnancy in the Cow

Background: The presence of conceptus alloantigens necessitates changes in maternal immune function. One player in this process may be the macrophage. In the cow, there is large-scale recruitment of macrophages expressing CD68 and CD14 to the uterine endometrium during pregnancy. Methodology/Principal Findings: In the present study, the function of endometrial macrophages during pregnancy was inferred by comparison of the transcriptome of endometrial CD14 + cells isolated from pregnant cows as compared to that of blood CD14 + cells. The pattern of gene expression was largely similar for CD14 + cells from both sources, suggesting that cells from both tissues are from the monocyte/macrophage lineage. A total of 1,364 unique genes were differentially expressed, with 680 genes upregulated in endometrial CD14 + cells as compared to blood CD14 + cells and with 674 genes downregulated in endometrial CD14 + cells as compared to blood CD14 + cells. Twelve genes characteristic of M2 activated macrophages (SLCO2B1,GATM,MRC1,ALDH1A1,PTGS1, RNASE6, CLEC7A, DPEP2, CD163, CCL22, CCL24 ,a ndCDH1) were upregulated in endometrial CD14 + cells. M2 macrophages play roles in immune regulation, tissue remodeling, angiogenesis and apoptosis. Consistent with a role in tissue remodeling, there was overrepresentation of differentially expressed genes in endometrium for three ontologies related to proteolysis. A role in apoptosis is suggested by the observation that the most overrepresented gene in endometrial CD14 + cells was GZMA. Conclusions: Results indicate that at least a subpopulation of endometrial macrophages cells differentiates along an M2 activation pathway during pregnancy and that the cells are likely to play roles in immune regulation, tissue remodeling, angiogenesis, and apoptosis.