Role of eosinophils in uterine responses to estrogen

Administration of estradiol (E2) to ovariectomized mice results in a dramatic increase in uterine growth and an influx of eosinophilic leukocytes. This influx is mediated by stimulation of an E2-dependent eosinophilic chemotactic factor in the uterus (ECF-U). The role of this eosinophil infiltration in uterus is presently unknown but could involve early growth and/or remodeling processes. In an attempt to better define eosinophil function in uterine tissue, we produced ovariectomized mice severely depleted of circulating eosinophils by administration of a purified rat IgG monoclonal antibody against interleukin-5 (IL-5). Seven days later, animals were submitted to estradiol treatment. Experimental groups included mice treated with saline alone, saline followed by E2, IgG followed by E2, and anti-IL-5 followed by E2. Pretreatment with IL-5 antibodies led to no significant alteration in E2-induced increase in uterine wet weight. However, histological evaluation demonstrated a clear and almost complete blockade of E2-stimulated influx of eosinophils in anti-IL-5 treated animals. In addition, IL-5 antibody administration significantly reduced E2-induced increase in peroxidase activity. Dramatic reduction of eosinophils did not affect E2 stimulation of ECF-U activity by stromal cells or complement C3 synthesis by the epithelial cells. Thus, it appears that differences in E2 responses in eosinophil-deficient mice are not directly associated with presence or absence of eosinophils. Taken together, these data suggest that eosinophils most likely do not contribute to early growth in the E2-stimulated uterus. A possible role in other events such as remodeling remains to be elucidated.