Differentiation of the Endometrial Macrophage during Pregnancy in the Cow

Peter J Hansen,Lilian J Oliveira,Steve Mcclellan,Rupert Kaul

doi:10.1371/journal.pone.0013213

Abstract

BackgroundThe 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 FindingsIn 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, and CDH1) 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 over-representation 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.ConclusionsResults 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.

Highlights

Pregnancy leads to immunological adjustments in the mother that facilitate survival of the conceptus
Endometrial macrophages in the human have been proposed to participate in vascular remodeling since they produce vascular endothelial growth factor [13] and macrophage accumulation in the uterus is abnormal in women with pre-eclampsia [14]
As shown from results of hierarchical cluster analysis (Figure 2A), 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

Summary

Introduction

Pregnancy leads to immunological adjustments in the mother that facilitate survival of the conceptus One of these adjustments, recruitment of macrophages to the pregnant endometrium, occurs in a wide range of mammalian species including the mouse [1], human [2,3,4], cynomologus and vervet monkeys [5], sheep [6] and cow [7,8]. Given the potential antigenicity of the conceptus by virtue of inheritance of paternal antigens and, at least in cows, the expression of classical MHC proteins on the placenta [17,18], a role for macrophages in limiting activation of anticonceptus immune responses is possible. The presence of conceptus alloantigens necessitates changes in maternal immune function One player in this process may be the macrophage. There is large-scale recruitment of macrophages expressing CD68 and CD14 to the uterine endometrium during pregnancy

Methods

Results

Conclusion