Relationship between macrophage colony-stimulating factor production by uterine epithelial cells and accumulation and distribution of macrophages in the uterus of pregnant mice.

Estrogen and progesterone induce production of macrophage colony-stimulating factor (CSF-1) by uterine epithelial cells, and CSF-1 is produced in the uterus during pregnancy in mice. CSF-1 is a lineage-specific stimulator of macrophage proliferation, chemotaxis, and function. High concentrations of macrophages accumulate in the uterus during pregnancy. Experiments were conducted to determine whether a relationship exists between intrauterine CSF-1 production and the number and distribution of uterine macrophages during pregnancy in mice. The study demonstrated that on day 1 of pregnancy CSF-1 bioactivity levels were high. The number of macrophages in the uterus was also high on days 1 and 2, and macrophages were concentrated at epithelial surfaces. The decrease in CSF-1 bioactivity seen between days 1 and 2 was followed by a decrease in the macrophage concentration. An increase in CSF-1 bioactivity on day 4 was followed by an increase in the concentration of intrauterine macrophages. During the immediate postimplantation period, macrophages were detected primarily in the myometrium and deep endometrium and CSF-1 bioactivity was undetectable. During the second half of pregnancy, when CSF-1 concentrations were very high, the macrophage concentration was also very high and large numbers of macrophages were detected in association with epithelia. The data confirmed the existence of a direct relationship between intrauterine CSF-1 and macrophage accumulation and suggested that macrophages are attracted to epithelial surfaces by CSF-1.