Macrophages are constituents of all normal connective tissue including the murine uterus. Macrophages have been identified previously in endometrium and myometrium of pregnant and non-pregnant murine uterus using antibodies against macrophages. In the current study immunohistochemical analysis of murine uterus demonstrated that there were not significant quantitative differences in uterine macrophages between the diestrous, pro-oestrous and oestrous stages. However, distributional changes occurred during the oestrous cycle. Macrophages were evenly distributed throughout uterine tissue during dioestrus, while, during pro-oestrus and oestrus, their concentration was highest in the subepithelial stroma. Because the oestrous cycle is hormonally regulated, we asked whether or not oestrogen and/or progesterone might influence macrophage distribution. Ovariectomy, which eliminates cyclical production of oestrogen and progesterone, resulted in a significant decrease in both the relative and the absolute number of uterine macrophages within 6 days. Injections of progesterone or oestrogen to ovariectomized mice resulted in restoration of uterine macrophage numbers. Injection of oestrogen plus progesterone in a regimen known to prepare the uterus for receptivity for blastocyst implantation increased the number of macrophages to levels which were consistently higher than those seen during oestrus. Moreover, following hormone administration macrophages were more concentrated in the subepithelial stroma, a distributional pattern which was most evident following injection of both hormones. The results suggest that both oestrogen and progesterone promote quantitative and distributional changes in the uterine macrophage population.

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The concentration and distribution of F4-80 positive cells (macrophages) and common leukocyte antigen (CLA) positive (bone marrow derived) cells were assessed in mouse uterus between days 1 and 8 of pregnancy. High numbers of polymorphonuclear leukocytes and lymphocytes were present on days 1 and 2, but not thereafter. Granulocytes were found both in the endometrium and within the luminal epithelium. The percentage of total cells contributed by macrophages was high on days 1 and 2. That percentage decreased significantly on day 3, then increased again on day 5 and remained high through day 8. Macrophages always were found in myometrial stroma. Macrophages were found throughout the endometrium on days 2 through 8. High numbers of macrophages were observed near epithelia, particularly on days 1, 2, 4, and 5. Few F4-80+ or CLA+ cells were observed within the developing primary and secondary decidua. The results demonstrate that an inflammation-like cellular response occurs in the uterus following mating and that macrophages are a major cellular component of the uterus during early pregnancy.

Further, the data demonstrate the expression of genes for CSF-1, GM-CSF, IL-1\g=a\,IL-1\g=b\, IL-6 and TNF-\g=a\ is induced in the uterus during mating.