The effect of restricted nutrition on uterine macrophage populations in mice

The abundant macrophage populations present in the endometrium are implicated in the tissue remodelling events and immunological changes necessary for pregnancy. Using two regimens of restricted nutrition (95 and 88% of ad libitum intake for 19 days), we have shown that moderately reduced food consumption can dramatically alter the number of endometrial macrophages and their immunoaccessory function in mice. Restricted nutrition also interfered with the estrous cycle, but the effects on endometrial macrophages were more extensive and qualitatively different than could be explained by diminished ovarian steroid hormone activity. Significantly less F4/80+ and Ia+ cells were found in the endometrium of food restricted mice than in ad libitum mice at the same estrous cycle stage. In the more severely restricted mice the losses were even greater than those seen after ovariectomy. In ad libitum fed animals, uterine but not peritoneal macrophages showed an ovarian hormone-dependent inhibitory phenotype in a splenocyte mitogenesis assay. Macrophages derived from both locations exhibited greater immunostimulatory activity following restricted nutrition. We conclude that endometrial macrophage populations are influenced by nutritional status and this may be mediated through both steroid hormone-dependent and -independent mechanisms. Nutritionally induced aberrations in the number or behaviour of endometrial macrophages during the estrous cycle or in early pregnancy could have important implications for the quality of the pre- and peri-implantation environment and the maternal immune response to pregnancy.