Endotoxin-induced abortion in mice is mediated by activated fetal macrophages

Leukocyte numbers and function were assessed in uterus, placenta, and fetus during endotoxin-induced abortion. Tissues initially contained high numbers of macrophages but no granulocytes or lymphocytes. Endotoxin treatment resulted in rapid, transient neutrophil accumulation in uterus and placenta. Moderate increases in macrophage numbers occurred in the uterus but there were no changes in tissue distribution. Myometrial, endothelial, and epithelial cells were unaffected by endotoxin but proliferating, differentiated fibroblasts that made up the primary decidua disappeared. As abortion progressed, the proportional representation of macrophages in placenta and embryo increased until, during the late stages of fetal resorption, they constituted nearly all viable fetal cells. At the same time, overall expression of class II major histocompatibility complex gene products increased in maternal and fetal tissue. Leukocyte distribution and macrophage activation data suggested that endotoxin-induced fetal failure is mediated by products of activated maternal and fetal macrophages acting in concert to destroy actively proliferating maternal and fetal cells.