Ovarian steroid hormone-regulated uterine remodeling occurs independently of macrophages in mice

Published online before print July 24, 2014Macrophages are abundant in the uterine stroma and are intimately juxtaposed with other cell lineages comprising the uterine epithelial and stromal compartments. We postulated that macrophages may participate in mediating or amplifying the effects of ovarian steroid hormones to facilitate the uterine remodeling that is a characteristic feature of every estrus cycle and is essential for pregnancy. Using the Cd11b-Dtr transgenic mouse model with an ovariectomy and hormone replacement strategy, we depleted macrophages to determine their role in hormone-driven proliferation of uterine epithelial and stromal cells and uterine vascular development. Following diphtheria toxin (DT) administration, approximately 85% of EMR1-positive (EMR1⁺) macrophages, as well as 70% of CD11C⁺ dendritic cells, were depleted from Cd11b-Dtr mice. There was no change in bromodeoxyuridine incorporation into epithelial cells induced to proliferate by administration of 17beta-estradiol (E2) to ovariectomized mice or into stromal cells induced to proliferate in response to E2 and progesterone (P4), and the resulting sizes and structures of the luminal epithelial and stromal cell compartments were not altered compared with those of leukocyte replete controls. Depletion of CD11B⁺ myeloid cells failed to alter the density or pattern of distribution of uterine blood vessels, as identified by staining PECAM1-positive endothelial cells in the uterine stroma of E2- or E2 combined with P4 (E2P4)-treated ovariectomized mice. These experiments support the interpretation that macrophages are dispensable to regulation of proliferative events induced by steroid hormones in the cycling and early pregnant mouse uterus to establish the epithelial, stromal, and vascular architecture which is critical for normal reproductive competence.Alison S. Care, Wendy V. Ingman, Lachlan M. Moldenhauer, Melinda J. Jasper, and Sarah A. Robertso