Macrophage colony stimulating factor controls macrophage recruitment to the cycling mouse uterus

Progesterone and estrogen induce uterine epithelial cells to produce macrophage colony stimulating factor (CSF-1), and mouse uterine epithelial cells produce large amounts of CSF-1 during embryo development. The present study demonstrated that estrogen and progesterone each induce uterine CSF-1 gene transcription and translation detectable by Northern blotting and bioassay. Intrauterine CSF-1 production was greater in the presence of both estrogen and progesterone than following exposure to either hormone alone. CSF-1 mRNA was detectable in the uterus throughout the estrous cycle while CSF-1 bioactivity was detected only during proestrus. CSF-1 production was directly related to the presence of macrophages in the uterus. Ovariectomy, which was rapidly followed by a loss of uterine CSF-1 gene transcription, also was followed by a dramatic decrease in the number of uterine macrophages. Both uterine CSF-1 and uterine macrophages were reconstituted in a dose-dependent manner by systemic administration of estrogen or progesterone. High concentrations of circulating estrogen and progesterone increased the number of macrophages in the uterus and increased their accumulation near epithelial surfaces. Similar relationships were observed in the uterus of cycling mice. Macrophages accumulated in the uterus following intraluminal injection of recombinant human CSF-1 to ovariectomized mice, directly demonstrating the ability of CSF-1 to recruit macrophages from peripheral blood into the uterus. These studies demonstrated that estrogen and progesterone stimulation of CSF-1 production by mouse uterine epithelial cells controls recruitment and distribution of macrophages in the uterus during the estrous cycle.