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 macro‐phages accumulate in the uterus during pregnancy. Ex‐periments 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 bioac‐tivity on day 4 was followed by an increase in the con‐centration of intrauterine macrophages. During the im‐mediate postimplantation period, macrophages were detected primarily in the myometrium and deep en‐dometrium and CSF‐1 bioactivity was undetectable. During the second half of pregnancy, when CSF‐1 con‐centrations 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.