Numerous growth factors are involved in mediating proliferation and differentiation of endometrial stromal cells during decidualization. During this period, the extracellular matrix of the endometrium undergoes extensive remodeling. We tested the hypothesis that epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor- regulate expression of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), during decidualization. Stromal cells were isolated from uteri hormonally sensitized to undergo decidualization and were cultured in the absence or presence of a growth factor. Using substrate-gel electrophoresis with gelatin as the substrate, we detected activity for gelatinase A and B, and collagenase-3, and using casein as a substrate, we detected activity for stromelysin-1. Increasing concentrations of EGF and bFGF resulted in increased activity of gelatinase B, collagenase-3, and stromelysin-1. Northern blot analyses revealed that EGF and bFGF also increased messenger RNA levels for these MMPs. There was no effect of these growth factors on gelatinase or TIMP-1, -2, and -3, nor was there an effect of transforming growth factor- on any MMP or TIMP examined. These data demonstrate that EGF and bFGF increase levels of proteolytic enzymes produced by endometrial stromal cells undergoing decidualization in vitro while having no effect on their inhibitors. (Endocrinology 141: 629 -636, 2000) D URING EMBRYO implantation in rodents, the stromal fibroblast cells of the endometrium proliferate and differentiate into decidual cells, a process that ultimately results in the formation of the maternal component of the placenta (1). Several lines of evidence indicate that this process, in addition to being regulated by estrogen and progesterone, is also regulated by several locally produced growth factors. There is increased binding of epidermal growth factor (EGF) to the uterus during decidualization (2), and this factor is able to induce embryo implantation in the absence of estrogen (3). The messenger RNA (mRNA) for basic fibroblast growth factor (bFGF) is present in the uterus during early pregnancy (4), and its levels increase substantially during decidualization, specifically within the mesometrial decidual cells (5). The expression of bFGF in the uterus is regulated by progesterone, and bFGF is involved in controlling both stromal cell proliferation (6) and angiogenesis (5). The mRNA for transforming growth factor- (TGF) is also present within the uterus during pregnancy and is localized to the luminal and glandular epithelial cells during early decidualization and to macrophages during midgestation (7).During decidualization, the extracellular matrix (ECM) of the endometrium undergoes extensive remodeling, whereby the fibrillar collagen underlying the undifferentiated stromal cells becomes less fibrous due to the removal of several collagen components from the matrix (8). Subsequently, the newly differentiated decidu...