The abundant macrophage populations present in the endometrium are implicat
ed in the tissue remodelling events and immunological changes necessary for
pregnancy. Using two regimens of restricted nutrition (95 and 88% of ad li
bitum intake for 19 days), we have shown that moderately reduced food consu
mption can dramatically alter the number of endometrial macrophages and the
ir immunoaccessory function in mice. Restricted nutrition also interfered w
ith the estrous cycle, but the effects on endometrial macrophages were more
extensive and qualitatively different than could be explained by diminishe
d ovarian steroid hormone activity. Significantly less F4/80 + and Ia + cel
ls 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 libi
tum fed animals, uterine but not peritoneal macrophages showed an ovarian h
ormone-dependent inhibitory phenotype in a splenocyte mitogenesis assay. Ma
crophages derived from both locations exhibited greater immunostimulatory a
ctivity following restricted nutrition. We conclude that endometrial macrop
hage populations are influenced by nutritional status and this may be media
ted through both steroid hormone-dependent and -independent mechanisms. Nut
ritionally induced aberrations in the number or behaviour of endometrial ma
crophages during the estrous cycle or in early pregnancy could have importa
nt implications for the quality of the pre- and peri-implantation environme
nt and the maternal immune response to pregnancy. (C) 1999 Elsevier Science
Ireland Ltd. All rights reserved.