Role of eosinophils in uterine responses to estrogen

Abstract

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.

Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle

“…The importance of estrogen in provoking eosinophil chemotaxis into the uterus is clear (Tchernitchin et al 1974); however, the cellular mechanisms and the functions of this uterine phenomenon remain poorly understood. Two molecules required for estrogen-dependent chemotaxis of eosinophils into the uterine stroma are interleukin-5 (IL-5; Perez et al 1996) and eotaxin (Gouon-Evans & Pollard 2001). In IL-5-and eotaxin-deficient females, the virtual absence of eosinophils has little or no effect on structure-function relationships in the uterus.…”

Ultrastructural Changes in the Uterine Luminal and Glandular Epithelium during the Oestrous Cycle of the Marsupial <i>Monodelphis domestica</i> (Grey Short-Tailed Opossum)

“…Early responses to oestrogen in the uterus of rodents include changes in vascular permeability, cellular infiltration and water uptake in the stroma [Yanagimachi and Chang, 1963;Sawicki et al, 1988;Perez et al, 1996]. The number of intraepithelial leucocytes and the time of their maximum appearance seem to be species dependent.…”

Genetic control of estrogen‐regulated transcriptional and cellular responses in mouse uterus

“…The early rapid phase, which occurs within 6 h of E 2 stimulation, is characterized by changes in gene transcription, a marked increase in vascular permeability, and water imbibition (3, 4). The late‐phase response, which occurs 18 to 30 h after E 2 stimulus, is characterized by an influx of leukocytes into the uterine stroma, changes in transcription of late‐phase genes, and an increase in epithelial cell proliferation and differentiation (4, 5). In addition, each phase of the uterotropic response is associated with distinct transcriptional signatures, implicating unique sets of differentially expressed genes in each of the physiological effects of E 2 (6).…”