Complexity in uterine macrophage responses to cytokines in mice

Uterine stromal macrophages change dramatically in density and morphology through the estrous cycle and during early pregnancy, whereas those in the mesometrial triangle do not undergo these changes. The mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1), regulates both the density and morphology of uterine macrophage populations, as shown by the fact that uterine macrophages are depleted and more rounded in the absence of CSF-1 caused by the osteopetrotic (csfm(op)) null mutation, compared to those of normal mice. Restoration of circulating CSF-1 to the nullizygous mice did not affect stromal macrophage density although it restored the population in the mesometrial triangle. This suggests CSF-1 regulation of these macrophage populations by local and humoral routes, respectively. Nevertheless, even in the absence of CSF-1, stromal macrophage population density varies 30-fold through the estrous cycle, suggesting the involvement in their regulation of factors other than CSF-1, such as the chemokines, which are chemoattractive for macrophages. The mRNA for the chemokines JE (MCP-1), C10, RANTES, and MIP1α are expressed in the uterus, with elevated levels observed on the first day of pregnancy. Such molecules, together with CSF-1, may play a role in modulating the complexities of uterine macrophage dynamics in response to sex steroid hormones and mating.